PAIN EDUCATION Module 2: Multimodal management of chronic pain

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1 The full version of this slide deck in MS PowerPoint format (containing presentation view and expanded notes) can be downloaded on please register! PAIN EDUCATION Module 2: Multimodal management of chronic pain

2 2013 Excerpta Medica BV The material presented in this teaching slide deck is for educational purposes only. If you wish to reproduce, transmit in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, any part of the material presented, you will need to obtain all the necessary permissions by writing to the publisher, the original author, or any other current copyright owner. Please cite as: PAIN EDUCATION Teaching Slides, chapter: Multimodal management of chronic pain, Available from No responsibility is assumed for any injury and/or damage to persons or property as a matter of products liability, through negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. Because of rapid advances in the medical sciences, it is recommended that independent verification of diagnoses and drug dosages should be made. Produced by Excerpta Medica Radarweg NX Amsterdam Netherlands Supported by an unrestricted educational grant from Grünenthal. Produced in the Netherlands

3 Learning objectives Upon completion of this training module you should have gained an increased understanding of: The multifactorial nature of chronic pain The importance of effective and early treatment of chronic pain The importance of a comprehensive approach to chronic pain management Non-pharmacological treatment Risks and benefits of different pharmacological options for pain treatment Factors influencing the success of pharmacological treatment For additional information and further educational content related to the multimodal management of chronic pain, please see Module 2 of the CME-accredited e-learning PAIN EDUCATION modules, available at

4 Comprehensive pain assessment and effective communication Foundations of effective pain management are: Good communication between physician and patient Understanding of the patient s situation, and individualizing treatment goals Multidimensional assessment of chronic pain Evaluation of the impact of chronic pain on patient function, well-being, and quality of life Create treatment plans based on: An understanding of the patient s pain characteristics An appreciation of underlying pain pathology and mechanisms Patient-physician treatment goals 1

5 Acute and chronic pain Pain persistence Acute pain Chronic pain Cancer pain Non-cancer pain Signals tissue damage Serves a protective function Signals increased nervous system activity Resolves upon healing No longer serves a useful purpose Persists beyond the expected period of healing Secondary to physiological changes in pain signaling and detection Degrades health and function World Health Organization Woolf CJ, et al. Proc Natl Acad Sci USA. 1999;96: Woolf CJ, et al. Anesthesiology. 2001;95:

6 Mean EQ-5D health state value Preview for Physical and psychological burden of severe pain Patients with chronic pain have one of the lowest observed health-related quality of life ratings of any medical condition, and place a heavy burden on health services Chronic pain affects the quality of working and social life Reduced mobility Sleep disturbances Appetite disturbances Anxiety and depression Absenteeism from work Cross-sectional European survey > 600 participants Increased severity of pain significantly reduced 0,8 quality of life 0,6 0, , Mild Moderate Severe Becker N, et al. Pain. 1997;73: Carmona L, et al. EPISER Study Group. Ann Rheum Dis. 2001;60: McDermott AM, et al. Eur J Pain. 2006;10:

7 Patients (%) Preview for Nociceptive and neuropathic pain components Accurate diagnosis of neuropathic pain is a milestone in choosing appropriate therapy n = 1,131 n = 4,254 n = 2, Mild Moderate Severe Mainly neuropathic Unknown Mainly nociceptive 4 Freynhagen R et al. Curr Med Res Opin. 2006;22:

8 Goals of chronic pain treatment The goals of chronic pain management differ from those of acute pain management Goals of chronic pain treatment include achieving a reduction in pain and changing in the patient s pain experience Patient and physician partnership Reduction of pain and a combination of coping strategies Individualized therapeutic aims and goals of reverting/preventing pain chronification Improved QoL and function Clark TS. Proc (Bayl Univ Med Cent). 2000;13: Gunreben-Stempfle B, et al. Headache. 2009;49: Mattenklodt P, et al. Schmerz. 2008;22: Muller-Schwefe G, et al. Current Medical Research & Opinion. 2001;27:

9 Importance of early and effective pain treatment Chronic pain may lead to intractable chronic pain states if not efficiently treated Chronic pain is associated with brain atrophy 5 11% reduction in grey matter volume in chronic back pain patients vs control subjects A failure to treat chronic pain effectively at an early stage can result in the development of pain that is more difficult to treat It is important in the clinical management of pain to identify, early on, factors that may leat to unsuccessful treatments and negative outcomes Schulte E, et al. Eur j Pain. 2010;12e Tracey I, et al. J Pain. 2009;10: Apkarian AV, et al. J Neurosci. 2004;24:

10 Multimodal treatment strategies for chronic pain patients Psychological therapy (relaxation, hypnosis, cognitivebehavioural interventions) Active physiotherapy and movement therapy (sports) Education of the patient and relatives Patientphysician relationship and optimal pharmacologic al treatment Peripheral stimulation and interventional therapy (acupuncture, spinal cord stimulation) The aim of multimodal therapy is to help patients improve functionality and to promote patient responsibility for managing disease Argoff CE, et al. Pain Med. 2009;10:S Dickman A, et al. Chronic Pain. Oxford Pain Management Library; Gatchel RJ, et al. J Pain. 2006;7: Dworkin RH, et al. Arch Neurol. 2003;60:

11 Pharmacological elements Pharmacotherapy Prostaglandin synthesis inhibitors NSAIDs Paracetamol Opioid analgesics Morphine Oxycodone Codeine Tramadol Ion channel blockers Lidocaine Reuptake inhibitors SSRIs SNRIs Pharmacological therapy should be seen as part of an integrated plan to: Improve physical and social functions Support a rehabilitative approach The choice should be based upon an analysis of the underlying pain mechanisms Argoff CE, et al. Pain Med. 2009;10:S Dickman A, et al. Chronic Pain. Oxford Pain Management Library; Gatchel RJ, et al. J Pain. 2006;7: Dworkin RH, et al. Arch Neurol. 2003;60:

12 Action sites of analgesics Pain is mediated through peripheral and central mechanisms Stimulation of peripheral nociceptors leads to transmission of pain signals to the brain via dorsal horn synapses in the spinal cord Analgesic agents can affect transmission, processing and perception of pain by Normalizing ascending amplification Supporting descending inhibition Changing cognitive processing of pain signals Gottschalk A, et al. Am Fam Physician. 2001;63: Kehlet H, et al. Anesth Analg. 1993;77: Dworkin RH, et al. Arch Neurol. 2003;60:

13 Analgesia and the pain pathway Pain development can be influenced by prostaglandin synthesis inhibitors Pain signalling and perception may be influenced by Drugs affecting the opioidergic system such as opioids, ion channel blockers, and neurotransmitter reuptake inhibitors Opioids Antidepressants Anticonvulsants Non-opioid analgesics Tramadol Codeine Morphine Oxycodone Amitriptyline Gabapentin Pregabalin NSAIDs Paracetamol metamizole The use of two or more agents with differing mechanisms or multiple modes of action increases the likelihood that pain signals will be interrupted and pain is relieved Gottschalk A, et al. Am Fam Physician. 2001;63: Kehlet H, et al. Anesth Analg. 1993;77:

14 Non-opioid analgesics Inhibition of the COX enzyme results in inhibition of prostaglandin synthesis COX inhibitors Non-acidic: paracetamol, metamizole Acidic (NSAIDs): ibuprofen, diclofenac Non-selective NSAIDs act on COX-1 and COX-2 NSAIDs only act on nociceptive pain and are not effective in chronic neuropathic pain Side effects of NSAIDs can include Gastrointestinal problems Cardiovascular effects, including myocardial infarction and stroke Allergic reactions Cholestatic hepatosis Leukocytopenia and aplastic anaemia NSAIDs must be used with caution in older patients with impaired renal function and heart failure Warner TD, et al. FASEB J. 2004;18: EMEA

15 Non-opioid analgesics in chronic pain An analysis of pain medication-use in Europe revealed that 96% of chronic pain patients were treated with analgesics not acting on the opioidergic system NSAIDs were the class of agent most frequently used 76% of chronic pain patients received NSAIDs as part of chronic pain treatment In 70% of the cases, therapy had to be changed because of inadequate pain control NSAIDs are not suited for long-term therapy for chronic pain because of their mode of action and the potential for serious side effects The EMEA recommends that the lowest effective dosage and short-term use of NSAIDs is to be preferred Rodriguez MJ. Rev Soc Esp Dolor. 2006;13: Breivik H, et al. Eur J Pain. 2006;10: EMEA

16 Other non-opioid analgesics Paracetamol Aniline derivative Widely used as an analgesic and antipyretic No significant antiinflammatory effects Metamizole Inhibitor of central prostaglandin synthesis Analgesic, antipyretic, anti-inflammatory, and antispasmodic effects Side effects Paracetamol is associated with risk of toxic liver damage at high doses Side effects Metamizole is associated with risks such as allergic agranulocytosis Mattia A, et al. Minerva Anestesiol. 2009;75: Rezende RM, et al. Br J Pharmacol. 2008;153:

17 Opioid analgesics Weak opioids Opioids Strong opioids Do not have a narcotic, or controlled-drug status Are often used in the management of musculo-skeletal and visceral pain Mainly effective in managing nociceptive pain Partially effective in relieving neuropathic pain Mainstay analgesic for control of post-operative pain and pain associated with cancer Have a controlled-drug status The use of opioid-based analgesia should only be part of an overall plan for management of chronic non-cancer pain World Health Organization IASP Chou R. Pol Arch Med Wewn. 2009;119: Varassi G, et al. 2010;26:

18 Opioids natural ligands Natural ligands for the opioid receptors are found in CNS Limbic system Thalamus Hypothalamus Striatum The spinal cord Formatio reticularis Substantia gelatinosa Peripherally Natural ligands include neuropeptides such as enkephalins, endorphins, and dynorphins Opioid receptors can be of μ,κ or δ subtype Opioid drugs act mainly via μ receptors Dickenson AH. In: Gebhart GF, et al., editors. Proceedings of the 7 th World Congress on Pain, Progress in Pain Research and Management pp Ananthan S. AAPS J, 2006;8:E

19 Opioids mechanism of action At presynaptic level, opioid binding leads to Reduced intracellular camp concentrations Decreased calcium ion influx Consequent inhibition of the release of excitatory neurotransmitters At post-synaptic level, opioid binding leads to Hyperpolarization of the neuronal membrane Decreased probability of action potential generation Opioids reduce pain signal transmission, activate descending inhibitory pathways and affect central pain processing Ananthan S. AAPS J, 2006;8:E Varassi G, et al. Curr Med Res Opin. 2010;26:

20 Opioid-induced side effects Common side effects of opioids: Nausea, vomiting Constipation Increased risk of respiratory depression Sedative/hypnotic effects Hypotension (orthostatic dysregulation) Decreased heart rate Cholestasis and micturnation disorders Urticaria Pruritus Bronchospasms in asthmatic patients Abnormal sensitivity to pain (hyperalgesia, allodynia) Bhamb B, et al. Curr Med Res Opin. 2006;22: Jacobsen R, et al. J Opioid Manag. 2007;3: Zöllner C, et al. Handb Exp Pharmacol. 2007;177:

21 Reuptake inhibitors tricyclic antidepressants (TCA) Tricyclic antidepressants: Inhibit neuronal uptake of noradrenaline and serotonin (5-HT) Are effective in managing chronic pain conditions including Neuropathic pain Complex regional pain syndrome Tension headache Are not related to antidepressants in terms of their analgesic effects Take 3 7 days for their analgesic effect to be seen Attal N, et al. EFNS Task Force. Eur J Neurol. 2006;13: Dworkin RH, et al. Arch Neurol. 2003;60: Varassi G, et al. Curr Med Res Opin. 2010;26:

22 Main TCA side effects Anticholinergic effects Dry mouth and nose Disturbed vision Constipation Urinary retention Cardiovascular effects Orhostatic hypotension Palpitations Tachycardia Disturbed conduction Weight gain CNS effects Dizziness Sedation Insomnia Tremor Convulsions Change in apetite Impaired liver function Sexual dysfunction Anaphylactic reactions Drug-drug interactions Attal N, et al. EFNS Task Force. Eur J Neurol. 2006;13: Dworkin RH, et al. Arch Neurol. 2003;60: Pickering G, et al. Clin Pharmacol Ther. 2006;79: Varassi G, et al. Curr Med Res Opin. 2010;26:

23 Selective serotonin and noradrenaline reuptake inhibitors SNRIs Are not associated with side effects linked with inhibition of adrenergic, cholinergic, or histaminergic systems May be better tolerated than TCAs Have moderate efficacy in pain management Have an analgesic effect mainly due to noradrenaline reuptake inhibition Are more effective in management of pain than SSRIs, because 5-HT has both inhibitory and facilitatory effects, and may thereby enhance pain Nausea Vomiting Constipation Somnolence Side effects Dry mouth Increased sweating Loss of appetite Weakness Quilici S, et al. BMC Neurol. 2009;9:6. Kishore-Kumar R, et al. pain. 1989;37: Watson CP, et al. 1985;23: Varassi G, et al. Curr Med Res Opin. 2010;26:

24 Anticonvulsants Effective in neuropathic pain and recommended as first-line analgesic in neuropathic pain conditions Binds to a subunit of presynaptic voltagedependent calcium channels Needs slow individual titration Used and recommended for first-line treatment in neuropathic pain conditions Provides its analgesic effect by interacting with N-type calcium channels Does not undergo hepatic metabolism Has a low risk of drugdrug interaction Blocks calcium and sodium channels Is indicated for neuropathic pain conditions Is a liver enzyme inducer May be associated with drug-drug interactions Sedation Dizziness Ataxia Ettinger AB, et al. Neurotherapeutics. 2007;4: Attal N, et al. EFNS Task Force. Eur J Neurol. 2006;13: Dworkin RH, et al. Arch Neurol. 2003;60: Side effects Peripheral oedema Nausea Weight increase Dizziness Fatigue Nausea Vomiting Side effects Arrhythmia Double vision Pruritus Changes in blood parameters 24 21

25 Topical analgesics Rubefacients NSAIDs Miscellaneous Traditional formulations based on salicylate and nicotinate esters, capsaicin and capsicum extracts and derivatives Diclofenac Felbinac Ibuprofen Ketoprofen Piroxicam Naproxen Flurbiprofen Benzydamine Mucopolysaccharide polysulphate Salicylamide Cooling sprays 22

26 Lidocaine 5% medicated plaster Mechanical protective component Soft plaster: barrier against skin rubbing, which provokes pain and allodynia Immediate cooling and soothing effect Mechanism of action Pharmacological component Lidocaine diffuses into the skin and blocks over-excitable Na + -channels on damaged nociceptors Stabilisation of neuronal membrane potential of A- and C-fibres, resulting in a reduction of ectopic activity At the long-term, reduction of peripheral input may counteract central sensitization Analgesia without anaesthetic effect (numbness) Acts locally directly at the area of pain Is indicated for neuropathic pain following a herpes zoster infection (postzoster neuralgia) Garnock-Jones KP, et al. Drugs. 2009;69: Scheuer T. J Physiol. 2007;581:423. Rowbotham MC, et al. Pain. 1996;65:

27 Other treatment options Capsaicin plaster Overstimulates TRPV1 channels Inhibits initiation of pain transmission in the spinal cord Ralfinamide Lacosamide Tapentadol Is a novel sodium channel blocker Is under investigation as a potential treatment for neuropathic pain Is an antiepileptic drug and an ion channel blocker Is under investigation as a potential treatment for neuropathic pain Is a centrally acting analgesic, combining 2 mechanisms of action μ-opioid receptor agonism (MOR) Noradrenaline reuptake inhibition (NRI) Hence, belongs to a new class called MOR- NRI Backonja M, et al. Lancet Neurol. 2008;7: Yamane H, et al. Exp Neurol. 2007;208: Harris JA, et al. Ann Pharmacother. 2009;43: Tzschentke TM, et al. Drugs Today (Barc). 2009;45:

28 Limitations of pharmacological pain management Drug treatment of severe chronic pain is often ineffective Balancing analgesic efficacy and drug tolerability Especially difficult if neuropathic component is present Dose titration may improve efficacy and tolerability Depending on patient-related factors such as underlying causes of pain, comorbidities, psychological state and drug responsiveness A clear understanding of possible factors involved in poor treatments and treatment discontinuations is important to optimize pharmacological treatment and outcome for the individual patient Reference 25 Varassi G, et al. Curr Med Res Opin. 2010;26:

29 The Vicious Circle: poor analgesia Pharmacological treatment Poor analgesia Side effects Adequate analgesia Reason: Wrong substance / wrong dose? Wrong diagnosis of pain type or components? Others? Poor efficacy Good tolerability Dose reduction Good efficacy + + Poor tolerability Dose increase Patient struggles but stays / Patient drops out opioid rotation Low quality of life Inefficient pain management and higher costs in health care system Varassi G, et al. Curr Med Res Opin. 2010;26:

30 The Vicious Circle: side effects Pharmacological treatment Poor analgesia Side effects Dose reduction Adequate analgesia Reason: Low tolerability? Interaction? Polymedication? Poor efficacy Good tolerability Dose increase Good efficacy + + Poor tolerability Patient struggles but stays / Patient drops out opioid rotation Low quality of life Inefficient pain management and higher costs in health care system Varassi G, et al. Curr Med Res Opin. 2010;26:

31 The Vicious Circle: adequate analgesia Pharmacological treatment Poor analgesia Side effects Adequate analgesia Dose reduction Still good treatment Analgesic tolerance Poor efficacy Good tolerability Good efficacy + + Poor tolerability Poor analgesia Dose increase Patient struggles but stays / Patient drops out opioid rotation Low quality of life Inefficient pain management and higher costs in health care system Varassi G, et al. Curr Med Res Opin. 2010;26:

32 Discontinuation % Preview for Treatment discontinuation Two studies on clinical trials investigating WHO step II and III opioids One in 5 patients discontinued due to adverse events % discontinued due to lack of efficacy ,5 10 Lack of efficacy Adverse events 5 0 Moore et al Kalso et al Moore RA, et al. Arthritis Res Ther. 2005;7:R Kalso E, et al. Pain. 2004;112:

33 Summary Early and effective pain treatment is important Treatment decisions should be based on underlying mechanisms and not only based on pain intensity A multimodal approach is needed for managing chronic pain which is a multifactorial condition Pharmacological therapy is a mainstay in the treatment of chronic pain Influencing factors for pharmacological treatment success need to be carefully considered Increasing awareness of the Vicious Circle among the medical community could reduce treatment discontinuation A referral to a multidisciplinary pain team should be considered 30