Analysis of perioperative risk factors for the development of acute and chronic postoperative pain

Transcription

1 Aus der Klinik für Anästhesiologie und Operative Intensivmedizin der Universität zu Köln Direktor: Universitätsprofessor Dr. med. B. W. Böttiger Analysis of perioperative risk factors for the development of acute and chronic postoperative pain Analyse perioperativer Risikofaktoren für die Entstehung akuter und chronischer postoperativer Schmerzen Habilitationsschrift zur Erlangung der venia legendi für das Fach Anästhesiologie an der hohen Medizinischen Fakultät der Universität zu Köln vorgelegt von Dr. med. Hans Jürgen Gerbershagen aus Mainz Köln 2010

2 Table of contents 1. General introduction Acute postoperative pain Chronic postsurgical pain Pain chronicity Outline of the thesis General methods Pain prevalence and risk distribution among inpatients in a German teaching hospital Prevalence, severity, and chronicity of pain and general health-related quality of life in patients with localized prostate cancer Preoperative chronic pain in radical prostatectomy patients - preliminary evidence for enhanced sensitivity to surgically-induced pain Risk factors for acute and chronic postoperative pain in patients with benign and malignant renal disease after nephrectomy Preoperative pain as a risk factor for chronic post-surgical pain six-month follow-up after radical prostatectomy Chronic pain and disability after pelvic and acetabular fractures - assessment with the Mainz Pain Staging System (MPSS) General discussion Summary / Zusammenfassung 59 List of abbreviations 74 Danksagung / Acknowledgements 75 2

3 1. General introduction Acute and chronic perioperative pain states are important causes of suffering. Despite the recent advances in postoperative pain management, the proportion of patients with moderate to severe postoperative pain is still high. In addition to being a process indicator for health-care quality and patient satisfaction, inadequate pain management contributes to the development of pulmonary 1;2 and cardiovascular complications, 3 surgical-wound infection 4 and can have long-term effects on healthrelated quality of life. 5 Since the publication of two reviews 6;7 indicating a high incidence of chronic postsurgical pain (CPSP), much attention has been drawn to this relevant outcome factor. Most patients who undergo surgery recover uneventfully and resume their normal daily activities within a few weeks. However, CPSP still develops in an alarming percentage of patients. In a multicenter trial, chronic pain patients were asked to give the perceived origin of their pain. Some 23% of these patients related their chronic pain to a surgical procedure, and 50% of this group regarded surgery as the single cause. 8 Similar results were demonstrated in a multicenter study by the German Society for the Study of Pain (DGSS) covering more than 10,000 chronicpain patients treated in 19 pain centers in Germany between 1998 and Surgery was regarded as the exclusive or a partial causal factor for the chronic pain condition in 30.6% of the cases. 9 A European telephone survey of the general population including more than 46,000 people and an in-depth interview of 4,839 patients with chronic pain (the latter defined as suffering from pain for longer than 6 months with a pain intensity on the numerical rating scale (NRS) of 5 or greater) revealed that CPSP ranked 10 th on the list of chronic pain causes, and was involved in 3% of cases Acute postoperative pain Definition There is no generally accepted definition of acute postoperative pain in terms of either temporal (e.g., hours, days or weeks following surgery) or intensity 3

4 parameters, for example, a distinct pain-intensity threshold. For this reason, a large number of different definitions of acute postoperative pain are used, and studies are difficult to compare. Prevalence and intensity of acute postoperative pain Postoperative pain control has frequently been shown to be inadequate in many countries. 11;12 In the last 20 years, much effort was made to improve the quality of postoperative pain treatment. Concepts of acute postoperative pain therapy are based on multimodal treatment with the use of various analgesics, epidural analgesia (EA), peripheral nerve blocks, training of nurses and physicians, and implementation of acute pain services. 13 Evidence-based pain-treatment strategies for specific surgical procedures are currently available. One guideline has been published by the Australian and New Zealand Society of Anesthesiologists ( the second has been presented by the Association of the Scientific Medical Societies in Germany (AWMF). 14 In a review, Dolin et al. included all postoperative pain studies dealing with major surgery and the application of patient-controlled analgesia (PCA), EA, or intramuscular analgesics. 15 They reported that in some 20,000 patients from 123 studies moderate pain (NRS 4 or VAS > 30 mm) was still present in 29.7% and severe pain (NRS 8 or VAS > 70mm) in 10.9% of cases. A large survey of the structural quality of pain therapy in 746 European hospitals did reveal ongoing improvement, with wide use of balanced analgesia and regular administration of analgesics. However, many limitations were still identified, e.g., a large number of hospitals (34%) still do not assess pain on a routine basis, which clearly indicates an urgent need for organizational improvement in postoperative pain therapy. 16 Risk factors To improve acute postoperative pain management in an individual patient, various possible risk factors have been analyzed. The identification of preoperative risk factors for more severe postoperative pain should facilitate early intervention and improve pain management. In a recent review, 47 studies were identified that analyzed preoperative risk factors for acute postoperative pain intensity. The review 4

5 indicated that pre-existing pain, anxiety, younger age, type of surgery, psychological distress, pain perception, and coping were the most significant predictive factors for the development of more severe acute postoperative pain. 17 Many of these predictors were confirmed by a large recent study on pain intensity in the initial minutes after awakening from anesthesia. 18 Kalkman et al. developed a prediction model including the risk factors younger age, female sex, higher preoperative pain intensity, type of surgery, preoperative anxiety, less need for information, and expected incision size larger than 10 cm. Each factor is weighted, and a total risk score can be calculated using a nomogram. 19 Preoperative pain Preoperative pain experience is a common predictor of more severe postoperative pain intensity. A positive correlation was found in a recent review 17 of six studies, and a negative correlation was found in only one report. 25 The definitions of preoperative pain, however, varied substantially, ranging from the presence of any chronic pain to pain greater than a defined pain-intensity threshold (e.g., VAS >30 mm), pain intensity in the region of surgery, 26;27 present pain intensity (PPI) of the McGill Pain Questionnaire, 23 and NRS value of any preoperative pain. 19 In most studies the relation of preoperative pain to the surgical site or to any other pain location is not mentioned. The studies cited above have measured pain preoperatively using merely unidimensional measures such as pain intensity or the presence of any pain (yes, no). The relation of the extent and impact of preoperative acute or chronic pain to acute postoperative pain has not been examined as yet. A comparison of preoperative pain conditions between different surgical departments has also not been studied to date. A cross-sectional study in a German university hospital measured the pain prevalence on one single day, thus including both preoperative and postoperative pain. 28 Only one study has examined the relation between preoperative chronic pain and acute postoperative pain intensities. 21 Chronic pain was defined as pain in any location that was present for more than 3 months before surgery. The influence of other pain locations on the emergence of acute postoperative pain is also not known. 5

6 1.2 Chronic postsurgical pain Definition The International Association for the Study of Pain (IASP) defines pain as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. 29 Up to now there is no generally accepted definition of chronic postsurgical pain (CPSP). Most attempts at defining CPSP in general 30 or specific to a surgical procedure 31;32 are descriptive in nature and offer a time frame in chronicity of 2 or 3 months after surgery. Macrae and Davis proposed the following four-point definition: 30 I. The pain developed after a surgical procedure II. The pain is at least of 2 months duration III. Other causes for the pain have been excluded IV. The possibility that the pain is continuing from a pre-existing problem should be explored and exclusion attempted The IASP defines chronic pain as persisting for longer than 3 months. Therefore, authors have often adapted their time frame for CPSP to 3 months after surgery. Unfortunately, only few studies have defined CPSP at all, and the results are not comparable. Incidence The incidence of CPSP varies from one type of operation to another and between studies, but it is clearly a common phenomenon. Table 1 shows the estimated incidence of chronic pain after some common operations. Table 1. Estimated incidences of CPSP and disability after common operations 33 Estimated incidence of CPSP Estimated incidence of severe (disabling) CPSP Amputation 30-50% 5-10% Breast surgery 20-30% 5-10% Thoracotomy 30-40% 10% Inguinal hernia repair 10% 2-4% Coronary artery bypass graft 30-50% 5-10% Cesarean section 10% 4% 6

7 The percentages of CPSP reported show great variability, which may be attributed to the criteria used to classify patients as having CPSP. Some studies included every patient who reported pain in the surgical site, while others included only patients with pain above certain intensities. Furthermore, only few studies examined the presence of preoperative pain, and thus it cannot be excluded that the reported CPSP was not a pain that had already existed preoperatively. To define persistent pain after surgery, other origins of pain than the surgery itself must be excluded, but this aspect of the definition of CPSP has also rarely been considered. Risk factors for CPSP Surgical factors The type of surgery and surgical approach may influence the incidence and intensity of CPSP. Intraoperative nerve injury can lead to persistent neuropathic pain; however, not every sensory-nerve lesion is followed by neuropathic pain. 34 Minimally invasive surgery has often been reported to successfully reduce the occurrence of acute postoperative pain compared to open procedures, although the long-term effect on CPSP remains inconclusive. Poor study designs often impede consensus on definite recommendations. Prospective studies comparing videoassisted thoracic surgery with open lung surgery failed to show an advantage for minimally invasive surgery in regard to CPSP. 35;36 Similarly, after inguinal hernia repair no differences in CPSP outcome were found between various open surgical procedures 37 as well as open versus laparoscopic surgeries. 38 However, a reduction in persistent postoperative pain was achieved for laparoscopic nephrectomies. 39;40 Preoperative psychosocial predictors Many preoperative psychosocial factors have been analyzed with regard to the development of CPSP. 41 Preoperative depression, psychological vulnerability, and stress seem most likely to be associated with CPSP. Four high-quality studies could demonstrate a relation between preoperative depression and the development of CPSP Nevertheless, many studies on the impact of preoperative psychological adaptation and stress on CPSP remain inconclusive because of contradictory 7

8 results. Other possible risk factors cannot be verified due to the small numbers of patients studied, including preoperative anxiety, health status and well-being, social support, and younger age. Preoperative factors that appear unlikely to be related to CPSP are female gender, neurotic state, lower educational level, and race. 41 Preoperative pain at the surgical site Prospective long-term studies in patients with phantom limb pain indicate a relation between preoperative pain in the extremity and the development of chronic phantom limb pain Higher preoperative pain intensities in the knee also predicted CPSP up to 1 year 27 and 2 years 49 after knee replacement surgery. In contrast, preoperative biliary pain was not a risk factor for CPSP after laparoscopic cholecystectomy. 26 The relation of preoperative pain in the inguinal region to CPSP after hernia repair remains unclear. Some retrospective studies reported an association between recalled preoperative pain some 2-7 years after surgery and CPSP, 5;50-53 although recalled pain should be regarded with caution. One large prospective study with regular follow-up for up to 5 years did not find a relation of CPSP to preoperative inguinal pain. 54 Overall acute preoperative pain A study analyzing the effect of preoperative pain on postoperative pain after various elective surgical procedures showed contradictory results. Higher pain intensity on the day before surgery was identified as being associated with a lower incidence of CPSP after 6 months. 55 Preoperative chronic pain Preoperative chronic pain at the surgical site has only been analyzed in lowerextremity amputation. The duration of preoperative leg pain showed inconsistent results with 46;47 and without 48 an influence on the development of phantom limb pain. Although preoperative pain seems to play a key role in the development of CPSP, only the presence, duration, or intensity of pre-existing pain have been recorded. However, the overall complexity of chronic pain with all its influencing biopsychosocial factors has not been examined as yet. 8

9 Acute postoperative pain One of the most consistent patient-related factors found to be associated with the development of CPSP is the higher intensity of acute postoperative pain in the days and weeks after surgery. 48;55-57 Impact of CPSP The impact of CPSP on the individual patient is not well studied to date. For example, although high incidences of CPSP are reported after thoracotomy, it must be considered that the majority of the patients have only low pain intensities. Painrelated interferences or functional impairment due to CPSP were rarely given attention. It is important to measure the patient s perception of the impact of CPSP in order to reveal the relevance of persisting pain after surgery. Katz et al. found a high incidence of CPSP after 6 and 12 months of 68% and 61%, respectively. These figures are consistent with other study results, although pain-related disability showed no change over time from the presurgical to the 3- and 6-month periods of postoperative follow-up of the total study group. 58 On the other hand, patients with CPSP after inguinal hernia repair reported a higher percentage of functional impairment and pain-related interference. 33 Prevention and therapy of CPSP Due to the frequently identified relationship of acute postoperative pain to CPSP, many attempts have been made to reduce CPSP in various types of surgery by means of intensifying perioperative pain management. A number of studies examined the effect of pre-emptive analgesia, where analgesic therapy is started before the surgical incision. The aim was to reduce CPSP by preventing central and peripheral pain sensitization. 59 To prevent chronic post-thoracotomy pain, preemptive EA, perioperative nerve stimulation, perioperative blocks of the intercostal nerves, intrapleural injection of local anesthetics, and ketamine were administered, but none led to sufficient prevention of CPSP. 60 Similar negative results were seen after radical prostatectomy As the results were not encouraging, new therapeutic approaches were sought, and preventive analgesia a broadly defined analgesic approach - was developed. This method should include multimodal techniques utilizing several drugs designed to reduce peripheral and 9

10 central hypersensitivity. It is important that the period of treatment is sufficiently long. 65 Based on the persistently unsatisfying outcomes in reducing the incidence of CPSP, a specific and direct relationship between the single factor of acute pain and CPSP cannot be assumed. Therefore, additional risk factors for the development of moderate to severe acute postoperative pain and CPSP must be analyzed in order to identify new methods of CPSP prevention and therapy. 1.3 Pain chronicity The IASP has arbitrarily defined pain as chronic if it is present for more than 3 months duration. 29 However, it is generally known that a temporal definition (e.g., 3 or 6 months) does not adequately reflect the complex bio-psychosocial associations involved in chronic pain disorders. Psychological factors such as anxiety, depression, neuroticism, medical factors such as comorbidity and number of pain locations, 66 as well as social factors like unemployment or level of education, among others, can impact chronic pain disease. Therefore, it is worthwhile to move away from the static dichotomous view of chronic pain and the survey question: Who has got it? toward the epidemiological question: How much of it has he got, and why?. Without this change of paradigm, the spectrum of severity of the total pain experience and the contribution of medical and psychiatric comorbidities will be missed. 67 Unfortunately, at the present time there is no generally accepted definition that can easily be applied to clearly identify or select chronic pain patients for study analyses. Pain chronification is the development of acute to chronic recurrent or persistent pain. Chronification describes a process with complex interrelations between biological, psychological, and social factors. The Mainz Pain Staging System (MPSS) is currently the only instrument that categorizes the extent of chronic pain disease using three pain chronicity stages (see chapter 2). The general applicability of the MPSS has been confirmed in many multi- and single-center trials in various kinds of pain syndromes

11 Due to non-uniform definitions of chronic pain, its reported prevalence shows considerable variation: the prevalence of chronic pain (> 3 months) was described in one review as ranging between 7% and 40%. 67 A European survey involving some 46,000 people indicated a prevalence of pain persisting for longer than 6 months with an intensity of NRS 5 of 19%. 10 As chronic pain has such a high prevalence in the general population, its possible impact on the development of acute and chronic postoperative pain warrants closer attention. As chronic pain patients comprise a very heterogeneous group, a detailed examination and description of the chronic pain syndrome is necessary to facilitate identifying patients at risk for developing severe acute postoperative pain and/or CPSP. The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) recommends six core outcome measures to fully characterize chronic pain populations and to enable comparison of study results. 74 Such detailed information on preoperative chronic pain as well as CPSP has not been analyzed to date. 1.4 Outline of the thesis In this thesis a series of studies systematically addressed several of the issues raised in the introduction. In chapter 3, we studied the prevalence and extent of chronic pain in four surgical and two medical departments to evaluate the patients preoperative pain status. In chapter 4, the influence of the etiology of chronic pain (tumor vs. non-tumor pain) was compared in patients with localized prostate cancer. In chapter 5, the influence of psychosocial factors and extent of pain chronicity on intensity and duration of acute postoperative pain was analyzed in patients undergoing radical prostatectomy. In chapter 6, the comprehensive bio-psychosocial complex of preoperative chronic pain was assessed to identify risk factors contributing to the development of more severe acute postoperative pain and CPSP after nephrectomy. In chapter 7, patients were followed up at 3 and 6 months after radical prostatectomy to evaluate the prevalence of CPSP and risk factors for its development. In chapter 8, posttraumatic pain several years after pelvic and/or acetabular fractures was analyzed as a similar model of chronic pain as CPSP and 11

12 the impact of chronic posttraumatic pain on patients everyday life. Furthermore, instruments were proposed to facilitate a measurement of general long-term outcome after posttraumatic pelvic fractures. In chapter 9, the implications of the studies described in this thesis with regard to patient care and future research are discussed. 12

13 2. General methods Assessment of acute and chronic pain, with its bio-psychosocial impact, was performed using validated instruments. These instruments were chosen following the recommendations of the Initiative on Methods, Measurement, and Pain Assessment (IMMPACT). 74 In addition, further validated measures were selected that are included in the pain questionnaire (Deutscher Schmerzfragebogen) of the German Society for the Study of Pain (DGSS) ( To reflect the complex biopsychosocial interrelations during the entire perioperative period, questionnaires with up to 80 items were completed by the patients. In addition to specific questions concerning CPSP or the surgery performed, the following questionnaires were used as modules in the study questionnaire. 1. Pain Average, worst, and current pain intensities were measured following the IMMPACT recommendations by means of the 11-item NRS with 0 = no pain, 10 = worst imaginable pain intensity at various time points. To enable comparison with studies using the temporal definition of chronic pain, the incidence of pain during the past 3 and 12 months was asked. The presence of pain was reported for 15 different predefined body areas. For prostatectomy, nephrectomy, and pelvic surgery more detailed additional body regions were included. A drawing in which pain sites (main, second, third, and further sites) were to be marked with different graphic symbols was completed by the patients. Patients reported all applicable reasons for the preoperative pain conditions, e.g., trauma, illness, psychological or physical distress, based on their personal judgment. 2. Assessment of pain chronicity Mainz Pain Staging System (MPSS) The MPSS, which differentiates three stages of pain chronicity 75 based on a tenitem, self-administered questionnaire taking into account temporal (patterns of occurrence, duration, change of intensity) and spatial (one, two, or multiple pain sites) dimensions of pain over a 4-week recall period; medication use (regular and irregular use of analgesics, opioids, and co-analgesics); previous drug withdrawal 13

14 treatments; and lifetime utilization of the health-care system (changes of personal physician due to insufficient pain management, pain-related hospitalizations, painrelated surgical procedures, pain-related and functional and occupational rehabilitation programs). The MPSS is a validated system that permits categorization of any chronic pain disorder. This questionnaire was developed by empirical assessment of 40 variables that were dependably associated with chronic pain. Pain data sets of 20,000 patients from the Interdisciplinary Pain Center of the German Red Cross, Mainz, Germany, were analyzed to determine factors associated with the pain chronification process. Principal component analysis revealed that ten items were assigned to four factors. Confirmatory factor analysis confirmed the four-factor solution. The MPSS model was extensively tested using linear regression analysis, logistic regression when appropriate, and graphic chain models. Scale statistics showed that three equidistant stages optimally demonstrate the development of chronic pain from mild, still low-risk pain to high-risk chronic pain with respective increasing degrees of physical, psychological, and psychosocial consequences. 68;75 At the present time, there is no other validated, clinically applicable instrument for measuring the process of pain chronicity. 3. Physical functioning Short Form 12 (SF-12) The SF-12 is a generic instrument measuring the mental and physical dimensions of health-related quality of life. 76 It is widely used in chronic pain studies. Chronic Pain Grading Questionnaire (CPGQ) The seven-item Chronic Pain Grading Questionnaire (CPGQ) was devised by von Korff et al. to specifically assess pain severity based on three measures each of pain intensity (current, i.e., at the time of questionnaire completion, average, and most severe pain intensities) during the previous 3 months and pain-related disability (usual activities; work activities including housework; recreational, social, and family activities), and number of days unable to perform normal activities. Employing the CPGQ, pain patients can be classified into one of four hierarchical categories: grade 1: low disability and low pain severity; grade 2: low disability and high pain severity; 14

15 grade 3: high disability, moderately limiting; grade 4: high disability, severely limiting. 77;78 Oswestry Low-Back-Pain Disability Questionnaire The Oswestry questionnaire focuses on a limited range of pain-related physical functions, which include walking, standing, sitting, lifting, self-care, travelling, sex life, and sleep in patients with low back pain 79 was used to examine outcome after pelvic fracture. 4. Emotional functioning Short Form 12 (SF-12) The SF-12 is a generic instrument measuring the mental and physical dimensions of health-related quality of life. 76 Hospital Anxiety and Depression Scale (HADS) The Hospital Anxiety (7 items) and Depression (7 items) Scale was used to screen for depression and anxiety symptoms. The HADS predominantly measures medium- and long-term changes of global anxiety and depression levels. This instrument was designed to measure affective states independent of physical symptoms. Cut-off points were used to identify cases for anxiety 11 and depression Habitual Well-Being Questionnaire (HWBQ) The HWBQ is a seven-item questionnaire covering negative and positive affect. 81 Symptom Check List (SCL) The eight-item SCL evaluates psychosomatic dysfunction Quality of pain Neuropathic Pain Scale (NPS) The ten-item NPS, which characterizes the main clinical signs and symptoms of neuropathic pain, was used. The score is converted to a score ranging from 0 to 100. The NPS classifies three categories: no neuropathic pain (0 40 points), possible (41 53 points), and probable ( points) neuropathic pain. 83 PainDetect PainDetect is a nine-item screening questionnaire for neuropathic pain with a maximum score of 38 points. Cut-offs are defined as < 13 points for nociceptive pain 15

16 and > 18 points for neuropathic pain; intermediate scores are considered ambiguous Comorbidity Weighted Illness Check List (WICL) The WICL collects data on the frequency of physical and mental comorbid conditions and comorbidity-related disability by adding the interference with activities of daily living (NRS 0-10) for each listed illness (German Pain Questionnaire Manual: 16

17 3. Pain prevalence and risk distribution among inpatients in a German teaching hospital Kathrin Gerbershagen, Hans Jürgen Gerbershagen, Johannes Lutz, Deirdre Cooper Mahkorn, Frank Wappler, Volker Limmroth, Mark Gerbershagen Clinical Journal of Pain (2009) 37 (4): Pain is estimated to be present in some 40% to 90% of medical inpatients Melotti et al. performed a study in an Italian teaching hospital that showed a 24-hour pain prevalence of 52%. 90 In a German university hospital a pain prevalence of 63% was reported by inpatients (24-h prevalence). 28 A study of neurological inpatients in Germany demonstrated a pain prevalence of 80%. 91 The aim of the study was to assess the prevalence of pain at admission. A preoperative evaluation of pain and comparison between different surgical departments had not been performed previously. Additionally, medical departments were included. Furthermore, not only the prevalence of pain, but also the total burden of chronic pain disease was assessed in order to generate a risk profile for these patients and to evaluate the need for interdisciplinary, multimodal pain therapy. Methods This survey was conducted in January and February 2006 in a 670-bed teaching hospital in the State of Thuringia, Germany. The self-administered questionnaire included the following modules: HADS, SF-12, MPSS, and CPGQ (see chapter 2). Four surgical (neurosurgery, orthopedics, spine, and thoracic surgery) and two medical departments (cardiology, pulmonary medicine) were included. Results A total of 438 of the 455 patients contacted could be included in this study. Pain during the last 3 months was present in 83.8% of cases; in 63.5% pain was the main reason for hospital admission. Almost all patients in the departments of spinal surgery, neurosurgery, and orthopedics reported having pain during the last 3 17

18 months. The prevalence of pain in the other departments was between 69% and 81% (table 1). Among the patients undergoing spinal surgery, 90% reported that pain was the main reason for the current hospital admission, followed by 87.5% of the orthopedic patients, 75.5% of the neurosurgical patients, and 59.3% of the cardiacsurgical patients. In the departments of pulmonary medicine (22.0%) and cardiology (31.8%) pain was a less common reason for admission. Table 1. Distribution of patients with and without pain in the past 3 months among the departments Department Pain in the last 3 months No pain in the last 3 months Total n % n % n Cardiac surgery Cardiology Neurosurgery Orthopedics Pulmonary medicine Spinal surgery Thoracic surgery Twenty-seven percent of the patients who indicated having pain in the past 3 months reported moderate pain of NRS 5 to 6 and 33% reported severe pain of NRS 7. One and two pain locations were reported by 26%, and three or more locations by 48% of the pain patients. Dysfunctional pain as defined by CPGQ grades 3 (high disability, moderately limiting) and 4 (high disability, severely limiting) were found in 69% of the pain patients (table 2). Patients in surgical departments showed higher severity grades than those in medical departments. The pain patients showed significantly lower overall physical health scores (SF-12: 32.7 vs points). Anxiety (9.4 vs. 7.2) and depression scores (7.2 vs. 4.9) indicated that pain patients had a significantly higher psychological burden. Table 2. Distribution of pain severity grades in the departments (percentages in parentheses) Pain severity grades Grade 1 n (%) Grade 2 n (%) Grade 3 n (%) Grade 4 n (%) Total n (%) Cardiac surgery 5 (35.7) 2 (14.3) 2 (14.3) 3 (21.4) ) Cardiology 12 (52.2) 2 (8.7) 4 (17.4) 4 (17.4) 23 (100) Neurosurgery 6 (13.0) 2 (4.3) 10 (21.7) 28 (60.9) 46 (100) Orthopedics 5 (17.2) 4 (13.8) 6 (20.7) 14 (48.3) 29 (100) Pulmonary medicine 15 (22.7) 6 (9.1) 22 (33.3) 19 (28.8) 66 (100) Spine surgery 10 (9.3) 9 (8.3) 25 (23.1) 62 (57.4) 108 (100) Thoracic surgery 2 (28.6) 2 (28.6) 3 (42.9) - 7 (100) Total 55 (18.8) 27 (9.2) 72 (24.6) 130(44.4) 293 (100) 18

19 Discussion Nearly 84% of the patients reported having pain in the previous 3 months. An incidence this high of pain in hospitalized patients has only rarely been documented. One of the main reasons may be that most of our patients were admitted to the departments of spinal surgery, orthopedics, and neurosurgery (more than 50% for spine surgery). To our knowledge, this study represents the first extensive analysis of acute and chronic pain in a non-selected patient population in a teaching hospital in Germany. The survey by Strohbuecker et al. conducted in a German university hospital allowed only a general statement regarding pain prevalence on the day of the interview. 28 The results of our study demonstrate that chronic pain plays an important role in inpatients. Comparable data concerning pain prevalence have been shown in previous studies among neurological inpatients. 92 The distribution of pain sites (26.3% one, 25.4% two, and 48.3% three and more sites) showed a tendency toward expansion of pain, which is one of the most reliable prognostic signs of progressive pain chronification. 9;66 In a multicenter WHO study, 22% of general medical patients reported having persistent pain, defined as pain present most of the time for a period of 6 months or more during the prior year. 93 Among these patients, 27.5% reported two sites and 40.3% three or more sites. A study of neurological inpatients showed that 38.2% reported two and 38.2% three or more pain sites. 92 The assumption that a single pain site is a predictor of low pain chronicity thus appears justified. 94 The high pain prevalences and intensities found in this study should raise awareness in regard to acute postoperative pain prevalences and intensities. It should be debated whether it seems realistic to generally aim at a mild pain intensity of NRS 4 or lower as an acceptable level of pain in the acute postoperative period when patients have suffered from severe pain for months and years before surgery and have already used analgesics for a long time. Due to the high burden of chronic pain, patients being screened should be thoroughly questioned about pain in all body regions, and not simply the main pain site. For example, patients with a herniated intervertebral disc admitted to hospital for surgery should be asked to name all additional pain sites apart from back and leg 19

20 pain. In most patients with chronic pain, concomitant pain localizations are the rule rather than the exception. 20

21 4. Prevalence, severity, and chronicity of pain and general health-related quality of life in patients with localized prostate cancer Hans Jürgen Gerbershagen, Enver Özgür, Karin Straub, Oguzan Dagtekin, Kathrin Gerbershagen, Frank Petzke, Axel Heidenreich, KA Lehmann, Rainer Sabatowski European Journal of Pain, 12, (2008): There are many studies examining cancer pain from a wide variety of tumor types, but the pain was usually presupposed to be of tumor origin without analyzing possible chronic non-tumor origin. Thus, although pain in cancer patients is now commonly studied, a further deficit remains. Pain analysis is usually focused on postoperative or other post-therapy outcome, and baseline data are generally missing. Even for prostate cancer - the most frequent cancer in men no preoperative pain data or chronic pain-associated bio-psychosocial factors had been evaluated preoperatively or at a comparable tumor-disease stage. Sandblom et al. published a study of pain prevalence in patients with advanced tumor disease in which the incidence was 42% in 1,181 patients with different stages of prostate tumor disease. Fifty percent of their patients were pain-free: about 50% received palliative treatment. The average pain intensity during the baseline week was rated as moderate and severe in 18% of the patients. 95 In another large-scale study, moderate to very severe daily pain was reported by 18% of patients with localized prostate cancer in the 24 hours preceding the interview and by 35% in the prior week. 96 The unavailability of clinical data on the presence and dissemination of cancer immediately before or somewhat close to the interview raises the question of whether or not the pain was actually caused by the malignant disease. The authors felt that in view of the study s aims, however, attribution of recently experienced pain to a malignant lesion is not crucial and distinguishing between pain ultimately traceable to treatment or the lesion itself was beyond the scope of this investigation. Daut and Cleeland reported pain prevalences of 30% in patients with localized cancer and 75% in patients with metastases

22 The severity of pain disorders in urology is usually studied by assigning patients to groups of metastasized or non-metastasized prostate tumors. A differentiation between tumor-induced or tumor-related pain and non-tumor pain has rarely been attempted. 61 The aim of this study was to compare patients with cancer pain and non-cancer pain and pain-free patients with regard to pain chronicity and its biopsychosocial impact and health-related quality of life. Methods Patients planned for radical prostatectomy (RP) at the Urology Department of the University of Cologne were extensively examined 1 to 2 days preoperatively and analyzed in terms of pain and its associated influencing factors: pain chronicity (MPSS), pain severity (CPGQ), pain-related disability, health-related quality of life (SF-12), anxiety and depression (HADS), comorbidity (WICL), and well-being (HWBQ) as well as socio-demographic variables. Tumor pain was defined as: 1) Pain in the lower abdomen and/or genital region, as only localized tumor disease was included in this study; 2) Patients should assess a realistic temporal association between the onset of pain and prostate cancer disease; 3) The European Association of Urologists recommends screening for metastases including bone scintigraphy and abdominal computed tomography (CT) when prostate-specific antigen (PSA) values exceed 20 ng/ml. Screening for metastases was routinely performed when PSA levels were higher than 10 ng/ml. When the frozen sections obtained during prostate surgery revealed more than one tumor-containing pelvic lymph node, the RP was abandoned and these patients were excluded from the study; 4) Patients were requested not to evaluate pain caused by dysuria. Results Eighty of 115 patients complained of pain in the previous 3 months; all but 2 of these patients reported having had pain in the last 12 months as well. All psychological variables, including physical and mental health (SF-12), well-being, anxiety, and depression, were highly significantly negatively influenced in the pain patients (table 1). 22

23 Table 1. Physical and mental health, psychological distress, number of comorbidities, and comorbidity-related interferences with daily activities in patients with localized prostate cancer without and with pain complaints No pain in last 3 months n = 35 (30.4%) Pain in last 3 months n = 80 (69.6%) Mean SD Mean SD p Value Well-being (FW-7) a) Physical component (SF12) a) < Mental component (SF-12 ) a) Anxiety (HADS) b) < Depression (HADS) b) Number of comorbidities < Comorbidity-related disability < Anxiety (HADS) 11 < 10 Depression (HADS) 10 n % n % < a) Lower values indicate reduced well-being and quality of life b) Higher values indicate increased anxiety and depression n.s. The frequencies of pain locations in descending order were the back, tumor area (lower abdomen), neck/shoulder, lower extremity, upper extremity, head/face, hip, and upper abdomen/thorax. The 80 pain patients not only showed differences compared to non-pain patients, but also showed significant differences in terms of the extent of pain chronicity. Among the patients with pain, 11.3% were in the highest chronicity stage III and another 38.8% were in stage II. The results shown in table 2 demonstrate that the MPSS maps the continuum of the psychological severity spectrum of pain quite well by displaying the distributions of psychometric test results in the three pain stages. It shows the progressive increase in psychological dysfunction with increasing chronicity of the pain disorder. Physical and mental health are significantly reduced in the progression of the severity and chronicity continua. The mean anxiety scores in stages II and III are pathological; anxiety and depressive disorders are more frequently observed. Average pain intensities and pain-related interferences with daily activities increase continuously from stage I to stage III. 23

24 Table 2. Physical and mental health dimensions and pain-related factors in the 3 pain chronicity stages (MPSS I - MPSS III) MPSS I MPSS II MPSS III n=40 (50.0%) n=31 (38.8%) n=9 (11.3%) Mean (SD) Mean (SD) Mean (SD) p Value Age 65.0 (7.6) 61.7 (5.5) 61.4 (7.5) 0.09 (n.s.) Well-being (FW-7) 26.5 (7.3) 17.8 (9.9) 23.1 (9.6) < Physical component (SF-12) 49.0 (7.7) 43.1 (10.7) 36.3 (7.3) < Mental component (SF-12) 50.7 (9.1) 42.0 (12.6) 36.8 (10.9) < Anxiety (HADS) 7.7 (2.7) 10.0 (2.3) 10.1 (2.3) Depression (HADS) 3.6 (2.6) 7.1 (4.2) 5.9 (4.2) < Number of comorbidities 4.8 (2.6) 5.8 (2.3) 6.9 (3.2) (n.s.) Comorbidity-related disability 12.2 (10.0) 19.9 (11.8) 30.1 (12.8) < Main pain: average intensity 3.9 (2.0) 5.0 (2.5) 5.2 (1.2) Main pain: interference with daily activities 2.0 (2.1) 4.7 (3.1) 5.4 (2.8) < Anxiety (HADS) 11 < 11 Depression (HADS) 10 < 10 n (%) n (%) n (%) 6 (15.0) 3 (85.0) 1 (2,5) 39 (97.5) 15 (48.4) 16 (51.6) 9 (29.0) 22 (71.0) 4 (44.4) 5 (55.6) 2 (22.2) 7 (77.8) Twenty-three patients (28.8% of all patients with pain) related their pain to the prostate cancer. Only three of all the pain and psychosocial factors studied indicated significant differences between cancer and non-cancer pain patients. Patients with prostate-cancer pain reported more reduced well-being and mental health, and had higher mean depression scores than non-cancer pain patients. For all other pain variables, including pain chronicity (MPSS, CPGQ), intensity, number of pain locations, pain-related interference, physical health, anxiety scores, use of analgesics, and comorbidity no significant differences were found. Discussion This study demonstrated that patients with localized prostate cancer have to be divided into a pain-free and a pain group in order to analyze potential differences in medical, psychological, and socio-demographic measurements. Among the patients with pain, 11.3% were in the highest chronicity stage III and another 38.8% were in stage II. Thus, the MPSS characterizes 50.1% of the patients as being chronic pain sufferers, i.e., patients also suffering from considerable bio-psychosocial consequences of their pain. According to the classification of the IASP, 29 the most convenient point of division between acute and chronic pain is 3 months. In the present study, only 2 patients had pain durations of less than 3 months and would be considered non- 24

25 chronic-pain patients. In other words, all but 2 of our pain patients would be classified as having chronic pain. This study shows that the differences in pain chronicity stages and pain severity grades among tumor and non-tumor pain patients are minor and that multifocal pain is also equally distributed. Thus, no essential differences could be demonstrated. Most studies of cancer pain still assume that the malignancy causes the pain that has the most severe impact, and thus disregard other acute or chronic pain states despite their well-known, powerful influence on quality of life, anxiety, depression, and social functioning. The largest epidemiological report on pain in prostate cancer patients did not differentiate between either the origin or the site of pain. 95 Considering that 50%-80% of the older population, including men with prostate cancer, suffer from chronic painful conditions. 91;98;99 it may be assumed that many patients in Sandblom s study did not necessarily complain about pain of tumor origin. In the present study, the average pain intensity in the previous week was the strongest predictive factor for health-related quality of life. 95 Our results confirm the influence of pain intensity, severity, and chronicity on health-related quality of life. Furthermore, we could also demonstrate that chronic non-malignant pain has the same negative impact as tumor pain. 25

26 5. Preoperative chronic pain in radical prostatectomy patients - preliminary evidence for enhanced sensitivity to surgically-induced pain Hans Jürgen Gerbershagen, Oguzhan Dagtekin, Jan Gärtner, Frank Petzke, Axel Heidenreich, Rainer Sabatowski, Enver Özgür European Journal of Anaesthesia (2010, in press) Moderate to severe acute postoperative pain is strongly associated with the development of CPSP, 26;100;101 which suggests that risk factors for the occurrence of severe acute postoperative pain need to be more closely examined. A relation between preoperative chronic pain in the surgical site and postoperative pain intensity has been demonstrated in patients with phantom limb pain. 47 The association of preoperative chronic pain disorders of any type with acute postoperative pain intensity has been studied by Caumo et al.. 21 The authors asked patients scheduled for elective abdominal surgery if they had had pain lasting longer than 6 months (yes or no only). This study revealed that the presence of chronic preoperative pain was associated with a higher risk for acute postoperative pain with a VAS score > 30mm (odds ratio 1.75). The validity of applying the exclusively unimodal temporal definition of chronic pain has been disputed, however. 69;102;103 This study hypothesized that patients with high degrees of chronic preoperative pain, i.e., patients in higher MPSS stages, are sensitized and may develop more intense acute postoperative pain after RP. Further possible risk factors for the development of severe acute postoperative pain may include preoperative pain intensity, pain in the surgical (urological) site, symptoms of anxiety and depression, and reduced health-related quality of life. Methods This was a cohort study of 92 men who were consecutively admitted to the Urology Department of the University of Cologne. The patients completed a questionnaire 1 to 2 days before undergoing RP. 26

27 Pain was assessed with patients at rest and after standardized mobilization at 24, 48, and 72 hours after surgery. Pain after mobilization was measured using the method described by Katz et al. by asking patients to roll from a supine to a lateral position and perform two maximal inspirations before rating their pain. 64 To avoid an arbitrarily chosen single day to analyze postoperative pain severity, we added the pain intensity scores over the first 3 postoperative days, as has been described previously. 20;24 Only one study has evaluated the full range of possible cut-off points for mild, moderate, and severe pain in a postoperative setting, yielding a range for moderate pain of NRS In accordance with this study, we used the cut-off NRS score of 4 or greater as indicating moderate to severe pain. The scores of the first 3 days after surgery were added to yield a total pain score (TPS, range 0-30). A TPS after mobilization (TPS-M) of 12 or greater was defined as indicating moderate to severe pain. This cut-off point was based on a pain rating of NRS 4 (moderate to severe pain) during the first 3 days. Due to the multiple comparisons performed, P values in this study were adjusted using the Bonferroni-Holms method: the P values of the seven potential risk factors examined were ranked, beginning with the smallest value. The largest statistical effect was then tested by α*=α/m (m = number of selected variables). The secondlargest significance level was obtained by α*=α/m-1 and so on, as long as the first tested variable had no significant effect. Our significance levels subsequently ranged from P = to Results Eighty-four patients met the inclusion criteria for further study analysis. The intensity of pain during mobilization decreased from a median NRS value of 4.0 to 3.0 (mean ± SD: 3.5 ±2.0 to 2.8 ±1.9) during the first 3 days after surgery. Average pain intensity at rest decreased from a median NRS value of 2.0 (mean ± SD: 1.8 ±1.5) on the first day to 1.0 (mean ± SD: 1.4 ±1.4) after 3 days. Higher preoperative chronic pain stages proved to be a significant risk factor for the development of moderate to severe postoperative pain (table 1). While 58.6% of preoperative high-risk chronic pain patients (MPSS II and III) reported TPS-M 12, only 16.4% of the TPS M < 12 group were in preoperative MPSS stages II and III. 27

28 This corresponds to an odds ratio of 7.2. The four groups no pain to MPSS III correlated slightly with regard to TPS-M (r = 0.30; P = 0.006) (fig 1). Preoperative anxiety and depressive mood were significantly associated with both moderate and severe postoperative pain. Physical, but not mental health (SF- 12) was related to TPS-M 12. The statistical effect of mental health ranked sixth among the seven possible risk factors examined (P = 0.033); the requested significance level at this stage was P = Table 1. Preoperative pain variables, health-related quality of life, anxiety, and depression associated with acute postoperative pain Pain parameters TPS-M < 12 n = 55 (65.5%) TPS-M 12 n = 29 (34.5%) p value Sig. level * Mainz Pain Staging System (MPSS) < No pain 23 (41.8) 4 (13.8) Stage I (low-risk chronic pain) 23 (41.8) 8 (27.6) Stage II (moderately high-risk chronic pain) 8 (14.6) 14 (48.3) Stage III (high- to very-high-risk chronic pain) 1 (1.8) 3 (10.3) Average pain intensity categories No pain 23 (42.8) 4 (13.8) NRS 1-3 (mild) 23 (42.8) 18 (62.1) NRS 4-6 (moderate) 9 (16.4) 5 (17.2) NRS 7-10 (severe) 0 (0.0) 2 (6.9) Preoperative pain in a urological site ** Yes 7 (12.7) 4 (13.8) No 48 (87.3) 25 (86.2) SF-12 a) Physical health component 50.5 ± Mental health component 50.0 ± ** HADS b) Anxiety 7.5 ± Depression 3.7 ± Categorical variables are presented as n (%), continuous variables as mean ± SD. TPS-M = cumulated NRS scores (total pain score) after mobilization of the first 3 postoperative days; NRS = Numerical Rating Scale; SF-12 = Short Form 12; HADS = Hospital Anxiety and Depression Scale * Significance level is analyzed with Bonferroni-Holms method for multiple-comparisons ** p-value is not significant (Mann-Whitney test) a) Lower values indicate reduced habitual well-being and quality of life. b) Higher values indicate increased anxiety and depression and more psychosomatic 28

29 Fig 1. Preoperative chronic pain from no pain to Mainz Pain Staging System stage III (MPSS) in relationship to acute postoperative pain intensity measured as total pain score during mobilization (TPS-M) during the first three postoperative days. Discussion Patients with higher preoperative MPSS pain chronicity stages were significantly at risk to develop moderate-to-severe postoperative pain during mobilization. A majority of patients (58.6%) with TPS-M 12 showed high-risk chronic pain stages (MPSS II and III) preoperatively, compared to only 16.2% in the TPS-M < 12 group (odds ratio 7.2). The only previous study that examined preoperative chronic pain as a risk factor for the development of more severe acute postoperative pain differentiated between the presence of pain for longer than 6 months or not. 21 However, the unidimensional temporal definition of chronic pain does not reflect the complexity of the bio-psychosocial impact of chronic pain disorders. 75;103;105 To our knowledge, our study is the first that demonstrates that not only the presence, but also the extent of pre-existing chronic pain may play an important role in the development of more intense acute postoperative pain. Many recent studies have dealt with central and peripheral sensitization in diverse chronic pain conditions. Quantitative sensory testing (QST), which measures pain perception and thresholds to cold, heat, and pressure, is the most commonly used procedure. Good evidence for reduced thresholds for perception and/or pain is available in particular for fibromyalgia, back pain, various types of headaches, and chronic whiplash-related pain These findings may also explain the increased postoperative pain perception of our patients with preoperative chronic pain 29

30 conditions. Most of the above-mentioned studies compared QST thresholds in pain patients to those of healthy controls. A large-scale follow-up study analyzed subjects who developed headache during a 12-year time period. These researchers showed both increased sensitization in patients with newly-developed headache disorders as well as incremental augmentation of pain sensitization from no pain to migraine, frequent episodic, and chronic tension-type headaches. 107 These data support our results and our hypothesis that postoperative pain perception is related to the extent of pain chronicity. However, pain thresholds related to MPSS stages have not as yet been published. Taken together these data indicate that any pain, conceived as a separate comorbidity with the likelihood of serious bio-psychosocial consequences, is a risk factor for postoperative pain independent of its etiology or its relationship to surgery. 30

31 6. Risk factors for acute and chronic postoperative pain in patients with benign and malignant renal disease after nephrectomy Hans Jürgen Gerbershagen, Oguzhan Dagtekin, Tim Rothe, Axel Heidenreich, Kathrin Gerbershagen, Moritz Hahn, Rainer Sabatowski, Frank Petzke, Enver Özgür European Journal of Pain (2009) 13 (8): Little is known about the development of persistent pain after nephrectomy. Most authors have utilized the unidimensional temporal definition of chronic pain of the IASP. Following this definition, the incidence of CPSP after open nephrectomy ranges from 4% to 27%. In a prospective study, 20% of patients reported CPSP 6 months after nephrectomy, 40 and in a cross-sectional study 4% suffered from chronic pain 49 (±16) months after surgery. 111 Surveys conducted many years after nephrectomy have indicated high pain rates. Thus, Chatterjee et al. described a prevalence of 24% on average 3 years after nephrectomy; 3% of these patients complained of severe pain requiring medical treatment. 112 Various perioperative analgesic methods such as pleural catheters for local anesthetic instillation, 113 intercostal nerve blocks 114, and pre-emptive analgesia with morphine, ketamine, and clonidine 115 did not show significant analgesic advantages over routine postoperative opioid treatment during the acute postoperative period after nephrectomy. Epidural analgesia (EA) could at least significantly reduce the pain on day 1 of the first 5 postoperative days. 116 Conclusive preventive analgesic strategies are not currently available for CPSP after nephrectomy. The identification of risk factors for the development of severe acute as well as chronic postoperative pain may be helpful in order to identify new approaches to reduce or possibly prevent CPSP. The aim of this study was to assess the associations between acute and chronic preoperative pain, preoperative psychological, psychosocial, and sociodemographic factors, medical comorbidities, and the occurrence of severe acute and chronic pain after open nephrectomy. 31

32 Methods A total of 46 patients scheduled for partial or radical nephrectomy with benign or malignant diagnoses were asked to participate. In addition to a clinical examination with a focus on pain, detailed sociodemographic, psychological, and pain variables were analyzed preoperatively, daily during the first postoperative week, and at 3 and 6 months postoperatively. Data analyses are largely descriptive due to the low sample size. Accordingly, the term significant in this context is a descriptive indicator of group differences without confirmatory validation. Results Of the 46 contacted patients, 35 could be included in the study; 7 had to be excluded because of incidents during the postoperative period that could have led to pain that could not be differentiated from CPSP, such as tumor recurrence. The average pain intensity in all patients declined continuously from NRS 3.2 (± 2.1) on day 1 to NRS 1.3 (± 1.1) on day 6 after surgery. Pain on movement (sitting or standing up) decreased from NRS 5.3 (± 3.0) to 2.6 (± 1.3) from day 1 to day 6. Except for anxiety, only preoperative pain-related disability correlated significantly with more severe postoperative pain (correlations of 0.60 and 0.47 for 2- and 4-day postoperative periods, respectively). All other perioperative psychosocial, sociodemographic, pain, and comorbidity factors did not affect postoperative pain intensity during the first week. On the day of discharge, 22 patients (62.8%) reported persisting acute postoperative pain. After 3 months the changeover point to chronic pain the number of patients with persistent postsurgical pain fulfilling the criteria of CPSP had decreased to 10 (28.6%) (fig 1). Average and worst intensity scores of CPSP were NRS 2.8 and 4.5, respectively. Three patients evaluated their average CPSP intensity and 7 rated their worst CPSP as NRS 4. The new postoperative chronic pain interfered with daily activities (NRS 4) in 4 patients. 32

33 Percentage of patients Postoperative month postoperative pain Fig. 1. Number of patients with persistent postoperative pain from discharge up to 6 months. Patients with CPSP after 3 months had significantly higher preoperative anxiety scores, but the number of patients with clinically relevant anxiety ( 11) and depression ( 9) scores was not significantly higher in the CPSP group. The SF-12 indicated significantly reduced physical health in CPSP patients. The other measured psychosocial factors well-being, mental health, and psychosomatic dysfunction revealed no significant differences. Patients who additionally received EA with pre-emptive and postoperative administration of sufentanil and ropivacaine did not benefit significantly in terms of observed CPSP frequency or occurrence. The pain intensities during the first postoperative week were more severe in patients who developed CPSP after 3 months. Patients without CPSP maintained their physical health status 3 months after surgery, whereas in patients with CPSP a further decline in physical health was recorded. Pre- and postoperative physical health differed significantly between the two patient groups. A similar trend was observed in habitual well-being and psychosomatic dysfunction scores. Patients without CPSP reported no changes in psychosomatic symptoms and had improved well-being, whereas CPSP patients attained even poorer results. After 6 months, 3 patients (8.6%) complained of persistent postoperative pain. This low incidence of CPSP allows only a descriptive statistical analysis (table 1). All preoperative psychosocial variables including anxiety, depression, mental and physical health, psychosomatic dysfunction, and habitual well-being as well as comorbidity yielded more unfavorable scores in CPSP patients. It is important to note 33

34 that the poorer health status of the three CPSP patients had already been present preoperatively; all of them reported mild CPSP intensities (NRS < 4), and only one complained of CPSP interfering with activities of daily living with NRS 4. Table 1. Descriptive statistics: differences in medical, psychological and pain variables in patients without CPSP and CPSP 6 months after nephrectomy. A) results before nephrectomy B) results 6 months after nephrectomy A) Preoperative parameters no CPSP CPSP at 6 months n = 32 (91.4%) n = 3 (8.6%) Physical health (SF-12) a) ± ± 3.34 Mental health (SF-12) a) ± ± Anxiety (HADS) b) 7.25 ± ± 1.15 Depression (HADS) b) 3.19 ± ± 6.24 Well-being (HWBQ-7) a) ± ± 6.82 Psychosomatic dysfunction (SCL-8) b) ± ± 5.56 Number of comorbidities (WICL) 4.12 ± ± 2.82 Comorbidity-related disability (WICL) ± ± 9.01 All preoperative pain conditions Average pain intensity (NRS 0-10) 2.00 ± ± 1.99 Worst pain intensity (NRS 0-10) 4.88 ± ± 2.00 Pain-related disability (NRS 0-10) 2.00 ± ± 4.72 B) Evaluation 6 months after surgery Physical health (SF-12) a) ± ± 8.79 Mental health (SF-12) a) ± ± 8.78 Anxiety (HADS) b) 5.7 ± ± 5.24 Depression (HADS) b) 8.4 ± ± 3.5 Well-being (HWBQ) a) ± ± 9.71 Psychosomatic dysfunction (SCL-8) b) ± ± 5.57 MPSS No pain 14 (42.4) 0 (0.0) Stage I 10 (30.3) 1 (33.3) Stage II 8 (24.2) 2 (66.7) Stage III 1 (3.0) 0 (0.0) Categorical variables are presented as n (%), and continuous variables are presented as mean ± SD. CPSP=chronic postsurgical pain. Descriptive statistics only due to the small number of CPSP patients. a) Lower values indicate reduced habitual well-being and quality of life b) Higher values indicate increased anxiety and depression and more psychosomatic dysfunction Discussion The values of average pain intensity and pain intensity on movement during the first 6 postoperative days were in accordance with other studies on cancer nephrectomy using a flank incision. 115 Preoperative anxiety has been identified as predisposing to more intense postoperative pain during the first days after surgery in procedures such as RP, 117 abdominal surgery, 21;118 breast-cancer surgery, 119 hysterectomy, 120 and cholecystectomy. 24 The proportion of patients reporting persisting pain 1 month after nephrectomy has ranged from 56% 39 to 78% 121 in other studies. The number of patients in our study complaining of pain after surgery declined continuously from 31% after 1 34

35 month to 28.6% after 3 months and 8.6% after 6 months. The incidence of CPSP after 6 months was low compared to other studies reporting frequencies of 4%, %, 40, 24%, 112 and 27%. 122 Various factors could have contributed to these differences. Only Dillenburg et al. collected data prospectively and followed up patients to exclude pain due to cancer recurrence; the other three studies were of cross-sectional design without the possibility to diagnose other causes of pain. Following the definition of Macrae that CPSP develops after surgery, other causes of pain should have been explored; the possibility that pain from a pre-existing problem is continuing must be excluded. 30 In our opinion, a careful presurgical examination is necessary to assess potential preoperative pain conditions in the surgical field. Preoperative pain in the kidney area was reported by 37.1% of our patients, who were fully able to distinguish between pre-existing and newly developing pain conditions. This is hardly possible for patients in retrospective or cross-sectional studies many years after surgery. Only two previous studies assessed the intensity of CPSP after nephrectomy. In one NRS scores were not presented, but effect sizes were used to indicate changes over time periods of 3 and 6 months. Hence, the data are not comparable. 40 Chatterjee et al. reported an average pain intensity of NRS 5.0 in 24% of patients with CPSP 3 years (on average) after nephrectomy. 112 It is noteworthy that 77% of their study population were cancer patients, and tumor recurrence was not excluded as a possible cause of pain. The exclusion of tumor recurrence in our study population may have contributed to the lower CPSP intensities (NRS 2.8 and 3.0 after 3 and 6 months, respectively). The only previously available data regarding risk factors for the development of CPSP after nephrectomy were confined to the assessment of different open and laparoscopic surgical techniques. 39;111;121;123;124 Patients in our survey who developed CPSP showed significantly higher anxiety scores before surgery than patients without CPSP, although the prevalence of clinically relevant anxiety was not different. The impact of preoperative anxiety on the development of CPSP has been described for different procedures such as RP, 61 total knee replacement, 27 breastcancer surgery, 101 and diverse other surgical interventions. 55 Health-related quality of life prior to localized cancer nephrectomy was reported to be comparable to that in an age-matched population and was not particularly negatively affected after 35

36 surgery. 123;125;126 When patients were divided into CPSP and non-cpsp groups, however, the preoperative and 3-month follow-up values indicated significantly poorer physical health in the pain group. Our non-cpsp patients showed similar quality-of-life scores to a German age-matched control group. 127 Acute severe pain in the immediate postoperative period after various procedures is often considered to be related to the development of persistent postsurgical pain (62,68,69). This association was also observed in our study. However, the role of postoperative pain intensity in the development of CPSP remains unclear. Whether or not this relation suggests insufficient acute postoperative pain management, neuroplastic changes triggered by surgery, or even an individual preoperative predisposition is still a matter of debate. The occurrence of CPSP after 6 months was low in our study compared to others. Preoperative psychosocial factors including mental and physical health, anxiety, depression, habitual well-being, and psychosomatic dysfunction were more unfavorable in patients with CPSP after 3 months compared to patients without CPSP. These results indicate that in addition to preoperative anxiety and physical health, other psychosocial factors might also be related to the occurrence of CPSP after nephrectomy. 36

37 7. Preoperative pain as a risk factor for chronic post-surgical pain six-month follow-up after radical prostatectomy Hans Jürgen Gerbershagen, Enver Özgür, Oguzhan Dagtekin, Karin Straub, Moritz Hahn, Axel Heidenreich, Rainer Sabatowski, Frank Petzke European Journal of Pain (2009) 13 (10): Randomized, controlled, double-blind trials (RCTs) of patients who underwent RP have been performed to examine the long-term influence of analgesic measures after 3 and 6 months, e.g., EA, 128 spinal anesthesia, 63;117 and pre-emptive low-dose ketamine, 64 for preventing CPSP. Further RCTs were conducted with continuous subfascial local anesthetic infiltrations 129 and pre-emptive amantadine 130 for preventing acute postoperative pain in the first 72 hours after surgery. Only EA 62;131 and amantadine 130 were associated with significant pain reduction during the hospital stay, but no method led to significant reductions in the incidence and severity of CPSP. Since perioperative analgesic therapy seems to have no influence on the development of CPSP after RP, more effort should be focused on identifying perioperative risk factors. Methods Patients scheduled for RP were preoperatively evaluated for acute and chronic pain and psychosocial factors. A total of 102 were screened, and 84 could be analyzed. CPSP was defined by the definition of Macrae and studied at 3 and 6 months following surgery. Data analyses are mainly descriptive due to the multiple comparisons performed. Results One hundred and two patients scheduled for RP were invited to participate in the study; 97 consented and 5 declined. A total of 13 patients did not complete the study. There was a response rate of 95% and 92% at 3- and 6-month follow-up, 37

38 respectively. Three months after surgery, 12 patients reported characteristic symptoms of CPSP; the average intensity was NRS 2.3 (± 1.2), with 2 patients rating their pain as moderate (NRS 4-6). At 6-month follow-up, only 1 of the 12 patients still complained of persisting postoperative pain. Fifty-seven patients (67.9%) reported having chronic pain preoperatively. The transition from acute to chronic pain was defined by a cut-off interval of 3 months duration in order to permit a comparison of our results with those in the literature. All patients with pain in the 3 months prior to surgery also complained of pain during the last 4 preoperative weeks. All patients with CPSP at 3-month follow-up had experienced chronic pain before surgery, compared to 62.5% of the patients who did not develop CPSP. Patients reporting CPSP in the 3-month follow-up period had preoperative moderate- to high-risk chronic pain (MPSS II and III) significantly more often (66.7%), and had high pain intensity or pain-related disability (CPGQ grades 2, 3, and 4) in 50% of cases. Patients who did not develop CPSP reported low-risk, less severe, and less disabling pain before surgery. Multiple pain sites at baseline were observed significantly more often in CPSP patients. Only non-urological pain sites were described as being related to surgery; these patients developed new CPSP after prostatectomy. All other attributed causes of chronic pain were not significantly different between CPSP and non-cpsp patients. Patients in the CPSP group had more psychosomatic symptoms (SCL-8) and decreased mental health (SF-12) than non-cpsp patients (table 1). There were no significant differences in depression, anxiety, and habitual well-being scores between the CPSP and non-cpsp groups. Test result scores pain chronicity, chronic pain grades, quality of life, psychosomatic symptoms, and habitual wellbeing were all significantly less favorable in the CPSP group 3 months after surgery (table 1). Patients with CPSP reported significantly reduced physical health (P = 0.008) and habitual well-being (P = 0.009) and increased psychosomatic symptoms (P = 0.022) and depression scores (P = 0.028) compared to baseline. Anxiety scores remained unchanged. Three months after surgery, 8 of the 12 patients with CPSP used analgesics (NSAIDs). Five of these patients took analgesics for CPSP, the other 3 because of other pain syndromes. No opioids or co-analgesics were used. Seventy-two patients no longer reported any postoperative pain 3 months after discharge from the 38

39 Percentage of patietns hospital. These patients remained stable compared to baseline scores except for physical health. Only 1 patient reported CPSP after 6 months (1.4% of all patients): a 56-year-old man who had a T2 prostate tumor indicated no pain at the urological site before surgery, and had no complications in the postoperative period. He had, however, listed six other pain sites before surgery. The baseline pain intensities were rated as mild to moderate (NRS < 5). Acute postoperative pain intensity was also low. At 6-month follow-up he reported severe pain (NRS 8). The scores of the mental health scale of the SF-12 indicated severe psychological distress at discharge 1 month 2 months postoperative pain 3 months 4 months 5 months 6 months Fig. 1. Prevalence of postoperative pain after discharge from the hospital to 6 months after surgery. CPSP was assessed at 3 and 6 months other time points of CPSP cessation were based on patients recollection. 39

40 Table 1. Preoperative pain characteristics influencing CPSP after 3 months no CPSP CPSP Pain measures n = 72 (85.7%) n = 12 (14.3%) P Value Any preoperative pain < No preoperative pain 27 (37.5) 0 (0.0) Preoperative pain 45 (62.5) 12 (100) Mainz Pain Staging System (MPSS) No pain 27 (37.5) 0 (0.0) Stage I (no to low-risk chronic pain) 27 (37.5) 4 (33.3) Stage II (moderately high-risk chronic pain) 17 (23.6) 6 (50.0) Stage III (high- to very-high-risk chronic pain) 1 (1.4) 2 (16.7) Chronic Pain Grading (CPG) No pain 27 (37.5) 0 (0.0) Grade 1 (low disability, low pain intensity) 30 (41.6) 6 (50.0) Grade 2 (low disability, high pain intensity) 3 (4.2) 1 (8.3) Grade 3 (high disability, moderately limiting) 9 (12.5) 3 (25.0) Grade 4 (high disability, severely limiting) 3 (4.2) 2 (16.7) Number of pain sites (last 4 weeks) No pain 27 (37.5) 0 (0.0) 1 site 17 (23.6) 3 (25.0) 2 sites 11 (15.3) 0 (0.0) 3 sites 17 (23.6) 9 (75.0) Preoperative pain in a urological site Yes 7 (9.7) 4 (33.3) No 65 (90.3) 8 (66.7) Pain is attributed to an operation Yes 0 (0.0) 3 (25.0) No 72 (100.0) 9 (75.0) Analgesics (last 4 weeks) Yes 15 (20.8) 4 (33.3) No 57 (79.2) 8 (66.6) Intensity categories of average pain No pain 27 (38.0) 0 (0.0) NRS 1-4 (mild pain) 32 (45.1) 9 (75.0) NRS 5-6 (moderate pain) 10 (14.1) 3 (25.0) NRS 7-10 (severe pain) 1 (1.4) 0 (0.0) Preoperative main pain site no pain 27 (37.5) 0 (0.0) Back 17 (23.6) 3 (25.0) Urogenital 7 (9.7) 4 (33.3 Neck / shoulders 8 (11.1) 0 (0.0) Hips / legs / feet 7 (9.7) 2 (16.6) Arms / hands 3 (4.2) 1 (8.3) Head / face 3 (4.2) 1 (8.3) Abdomen 0 (0.0) 1 (8.3) Only preoperative pain patients n = 45 (78.9%) n = 12 (21.1%) All pain conditions (NRS 0-10) Average pain intensity 3.02 ± ± Worst pain intensity 4.96 ± ± Occurrence of pain attacks (last 4 weeks) Once daily or less 22 (48.9) 4 (33.3) Several times a day 10 (22.2) 4 (33.3) Most of the day or continuous pain 13 (28.9) 4 (33.3) Duration of pain attacks (last 4 weeks) Several hours or less 38 (84.4) 9 (75.0) Several days up to a week 4 (8.9) 2 (0.0) More than a week or continuously 3 (6.7) 3 (25.0) Categorical variables are presented as n (%), and continuous variables are presented as mean ± SD 40

41 Discussion In this study, we found a prevalence of CPSP of 14% 3 months after RP. This rate is low compared to other studies. Incidences 3 months after prostatectomy of 10%, 26%, 33%, and 49% have been published. 61;63;131 Even after 6 months, pain was still reported in 10% 33% of cases. 63;64;132 Only 1 patient (1.2%) in our study group complained of persisting postoperative pain after 6 months. The differences in incidence may be attributed to discrepancies in the definition of CPSP. According to Macrae, CPSP as a complication of surgery may only be assumed if this pain had not been present before surgery. 30 The other prostatectomy studies, however, did not examine preoperative pain conditions. Thus, the possibility that the persisting postoperative pain was a continuation of pre-existing problems cannot be ruled out. This factor may have contributed to the higher CPSP incidence in the other studies. A number of studies have found a relation between preoperative pain and CPSP after hernia repair and hysterectomy when patients were asked many years after surgery (2 to 7 years later) to recall their preoperative pain intensity. 5;50-53 This methodological approach is questionable, as recalled preoperative pain 6 months after lower extremity amputation was shown to be considerably overestimated. 47 Another criterion of Macrae s definition requires the exclusion of other nonsurgery-related postoperative pain causes. In order to exclude causes of cancerrelated pain, we screened patients using CT scans, PSA levels, and careful urological examination to identify tumor recurrence. This approach may also have contributed to the lower incidence of CPSP in our study compared to others that did not try to exclude tumor spread. All the published data on CPSP intensity 3 or 6 months after RP are consistent. We could confirm a low mean CPSP intensity of NRS 2.3 in our patients, with only 2 rating their pain at NRS 4. Sixty-eight percent of our patients reported having chronic pain before RP. This prevalence is consistent with epidemiologic pain studies in older populations. 78;91;93 Our study indicates that any chronic preoperative pain defined as pain present for longer than 3 months is a predictor for the development of CPSP. The multimodal measurements of the chronicity (MPSS) and severity of pain (CPGQ) are also predictive of CPSP, and at the same time demonstrate that with increasing progression of pain burden the risk of CPSP also increases. Eight of our 12 CPSP patients at 3-month follow-up were allocated to MPSS pain chronicity stages II and 41

42 III, indicating that they were suffering from moderately high-risk to very high-risk chronic pain. Large prospective, long-term epidemiological studies have demonstrated multiple pain sites and widespread pain to be associated with increased pain chronicity. 75;99;133;134 Thus, patients with multiple preoperative pain sites and higher pain chronicity stages (MPSS) are at higher risk to develop an additional pain location. The surgery could serve either as a trigger, or as an accelerator of the pain chronification process in patients with CPSP. Additionally, large prospective epidemiological studies demonstrated that patients with increased mental disorders, 66 reduced quality of life, and psychosocial problems 135 develop more pain locations over some years. These results are also comparable in CPSP patients as they reported significantly poorer psychological scores before surgery. Non-CPSP patients had preoperative mental and physical health scores within the normal range (49.2 and 49.3, respectively) that were comparable to an agematched German control group (52.9 and 42.9, respectively). 127 Most studies have reported normative quality of life scores in the total study population before RP. 62;64;136 Although our total study population also showed normative scores, differentiating CPSP from non-cpsp patients revealed significantly lower mentalhealth scores and a tendency to reduced physical health in CPSP patients at baseline. Physical and mental health had significantly diminished further in CPSP patients after 3 months, while they remained stable in non-cpsp patients. Most other studies observed a decline in physical and an unchanged mental health status after 3 months. 61;117;136 Two RP studies analyzed the influence of preoperative anxiety (Haythornthwaite et al., 1998; Ene et al., 2006) and depression (Ene et al., 2006) and described these as risk factors for the persistence of postoperative pain. The significance of these results is limited, however, because the 6-month data collection of preoperative anxiety and depression scores was retrospective 61 and there were low correlations of worst pain and anxiety (r = 0.26) and depression (r = 0.31). 117 This study failed to show significantly higher preoperative anxiety or depression scores in CPSP patients. However, the impact of preoperative anxiety as a risk factor for CPSP has been demonstrated for other surgical procedures such as abdominal, breast-cancer, and knee-replacement surgery. 27;55;101 42

43 Finally these data are also in concordance with other studies showing a failure of EA to reduce the incidence of CPSP. 61;62;117;128 43

44 8. Chronic pain and disability after pelvic and acetabular fractures - assessment with the Mainz Pain Staging System (MPSS) Journal of Traumatology (2010, in press) Hans Jürgen Gerbershagen, Oguzhan Dagtekin, Jörg Isenberg, Niels Mertens, Enver Özgür, Henning Krep, Rainer Sabatowski, Frank Petzke Chronic pain after trauma, like CPSP, has been a neglected topic in pain medicine, 33 possibly due in part to the lack of a uniform definition. In all previous studies on outcomes of pelvic-ring fractures, unidimensional pain measurements were used such as pain on sitting, standing, or strenuous activities (yes, no); 137 pain intensity; time since onset of pain; or the Short Form-36 (SF-36) bodily pain subscale, which combines one item each of pain magnitude and interference The assessment of long-term outcomes after pelvic fractures poses a major challenge due to the varied extents and definitions of such fractures, e.g., AO (Arbeitskreis Osteosythesefragen) classification, complex or non-complex, the coexistence of sacral and/or acetabular fractures, as well as the great variability of concomitant visceral and soft-tissue injuries, injury-related comorbidities, and surgical techniques. Several outcome scores have been published, which generally are focused on pain, functional capacity, social role functioning, and radiological aspects. 138;143;144 The Pelvis Task Force of the German Society of Traumatology (GST) added a graded list of clinical functions, social role functioning, and radiological outcome findings and published a large-scale, multicenter study on pelvic injuries employing these outcome parameters. 141 To date, however, there is no generally accepted and, above all, validated score available to compare outcomes after pelvic fractures. The aim of this study was to characterize chronic pain after pelvic-ring fractures utilizing the MPSS. Three pelvic-fracture outcome scores were to be compared to the three MPSS pain stages as well as to the Oswestry Low Back Pain Score. In 44

45 addition, physical and mental functioning, psychological distress, and health-related quality of life were used to demonstrate the long-term impact of chronic pain. Methods Patients with a fracture of the pelvic ring who were admitted to the Department of Traumatology of the University of Cologne from January 1, 1999 to December 31, 2004 were contacted by mail and invited to take part in an extensive follow-up examination. Patients were asked to complete most of the questionnaires described in chapter 2 (MPSS, CPGQ, PainDetect, Oswestry Low-Back-Pain Disability Questionnaire, HADS, and SF-12). Posttraumatic pelvic pain (PPP) was defined as pain in the region of the pelvis, low back, hips, or lower extremities when a relationship between pelvic trauma and the pain could be demonstrated. A detailed history taking and physical examination were performed in order to differentiate the origin of PPP, pain due to trauma in the lower extremities or spinal structures, and pain of non-traumatic origin. Thus, for example, leg injuries with subsequent pain after non-pelvic musculoskeletal lesions, stump pain, phantom limb pain, or neuropathic pain due to peripheral nerve injury were not included in the definition of PPP. Current, average, and worst PPP intensities during the last 4 weeks were assessed. Three pelvic outcome scores were analyzed for comparison with the three MPSS stages and physical and psychosocial dysfunctions: (1) Majeed s outcome score: The first pelvic-fracture-specific outcome score was published in Five major criteria were selected, including pain (30 points), work (20 points), painful sitting (10 points), painful sexual intercourse (4 points), and standing (36 points). The total score is divided into 4 categories: excellent ( 85 points), good (70-84 points), fair (69-55 points), and poor (< 55 points) for initially employed patients. (2) The GST outcome score evaluates three dimensions: radiological findings, clinical findings, and social role function. 141 A sum of 2-7 points is possible; the authors established four outcome categories: excellent (7 points), good (6 points), fair (4-5 points), and poor (2-3 points). (3) Bürk s outcome score is a modified version of Majeed s score. 138 The five above-mentioned variables were modified to include sensory and motor deficits, 45

46 interference with sporting activities, and impairment of micturition and defecation. Clinical, functional, and radiological scores are weighted as 0.6, 0.25, and 0.15, respectively. The total point categories indicating excellent to poor outcome are the same as in Majeed s score. In all patients included into the study, thorough neurological and orthopedic examinations were carried out and documented in analyzable forms. Radiographs were used for grading fractures and dislocations and used in the GST and Bürk scoring systems. Statistical analysis of variance was performed to indicate differences between the groups no PPP to MPSS III. Due to the multiple comparisons (several possible risk factors for higher pain chronicity stages) performed in this study, P values were adjusted using the Bonferroni correction from P = 0.05 to P = Results During the study period, 189 patients with pelvic and acetabular fractures were treated. A total of 69 patients could be enrolled in the study. Eighty-four were not traceable, 30 did not respond, and 6 refused to complete the questionnaire. The 69 patients presented with 49 pelvic and 41 acetabular fractures. Isolated pelvic or acetabular fractures occurred in 28 and 20 patients, respectively; a combination of both fractures was diagnosed in 21. Complex trauma defined as concomitant soft-tissue and organ injury in the pelvic region was diagnosed in 22 patients (31.9%). Osteosynthesis was performed in 70.0% of all cases. Pain in the pelvis, lower back, hips, or legs attributed to the pelvic trauma was reported by 63.8% of the patients at a median interval of 52 (range 19-90) months after the injury. PPP intensities are shown in figure 1. Patients with PPP reported significantly more intense average and worst pain intensities with increasing MPSS stages (table 1). The PainDetect questionnaire identified 10 patients with probable neuropathic pain (> 18 points). Eleven patients could not definitely be allocated to either nociceptive or neuropathic pain mechanisms (13-18 points). The neurological examination revealed nerve injuries in 29 patients; 9 of these were diagnosed as having probable and 7 as having not sufficiently proven neuropathic pain. The 46

47 Oswestry questionnaire showed significant functional limitations related to the pelvic injury with increasing pain chronicity stages (r = 0.68, table 1). Thirty-six percent of patients in MPSS stage I used NSAIDs, whereas 64% of stage III patients used opioids as well as NSAIDs (table 1). All psychometric results were significantly more unfavorable with increasing pain chronicity (from no PPP to MPSS stage III). The physical and mental components of the SF-12 score correlated negatively with increasing chronic pain stage (r = -0.72; r = -0.58, P < 0.001, respectively). The incidence of clinically relevant anxiety (HADS 11) and depression (HADS 9) as well as average scores increased with higher PPP chronicity stage. The correlations between anxiety and depression symptoms and MPSS stages were r = 0.51 and r = 0.67 (P < 0.001), respectively. The total number of comorbidities, WICL disability index, and number of traumarelated comorbidities correlated moderately with progressing chronic pain disease (range: r = 0.43 r = 0.59, P < 0.001). When pelvic fractures including combined fractures with acetabular involvement were analyzed by AO classification, AO groups B and C were significantly associated with higher MPSS stages. When complex fractures were analyzed separately, similar increases in pain chronicity were observed. All three pelvic-fracture outcome scores correlated strongly from no PPP to MPSS stage III, ranging from r = 0.78 to 0.9 (P < 0.001). As the three pelvic outcome scores (Majeed, Bürk, GST) and the Oswestry questionnaire essentially focus on functional outcomes, comparisons were performed and showed high correlations ranging from r = 0.76 to 0.96 (P < 0.001). 47

48 100% 80% 60% 40% 20% 0% Pelvic# A Pelvic# B Pelvic# C AC# NRS 7-10 NRS 5-6 NRS 1-4 no pain 100% 80% 60% 40% 20% 0% Pelvic# A Pelvic# B Pelvic# C AC# NRS 7-10 NRS 5-6 NRS 1-4 no pain Fig 1. Intensity of a) average and b) worst chronic posttraumatic pelvic pain. Pain intensity is classified as mild (NRS 1-4), moderate (NRS 5-6), and severe (NRS 7-10). Pelvic# = pelvic fracture (AO classification); AC# = isolated acetabular fracture. 48