Preemptive Analgesia: Does it Prevent Chronic Pain? Prof. Dr. Maged El-Ansary Al Azhar Univ. Al Azhar university, Cairo, Egypt 1. President of Egyptian Society for Regional Anesthesia & Pain Medicine 2.President of African Association for the Study of Pain, AASP 3. Former Council Member of International Association for the Study of Pain, IASP 4. Secretary General of Arab Union for Pain Management, AUPM
History Crile GW. 1916 1 first described a possible relationship between intraoperative tissue damage and an intensification of acute pain and longterm postoperative pain, which is now referred to as central sensitization Clifford Woolf 1983 3 The evidence for a central component of post-injury pain hypersensitivity in experimental studies. Wall P. 1988 2 Proposed the concept of pre-emptive preoperative analgesia 1. Crile GW. Austin A Man An Adaptive Mechanism. New York, NY, USA: The Macmillan Company; 1916. 2. Wall PD. The prevention of postoperative pain. Pain. 1988;33:289 290. 3. Woolf CJ. Evidence for a central component of post-injury pain hypersensitivity. Nature 1983;306:686 8
Introduction Pain is complex body reaction It is personal and individualized Patients undergoing a surgical procedure are predisposed to pain postoperative Pain due to: to noxious stimuli experience. 1. Pre-existing pain (acute and chronic) 2. Psychological fear of recurring additional pain 3. Neurovascular tissue damage from a prior operation 4. As well as the extent of the surgery can all contribute to major postoperative discomfort
Why To Relief Post Operative Pain? 5 Prof. M. El-ansary, Al-Azhar University Friday, October 09, 2015
6 Prof. M. El-ansary, Al-Azhar University Friday, October 09, 2015
Pain & Stress Pain Stress Response Infection 7 Prof. M. El-ansary, Al-Azhar University Friday, October 09, 2015
Pain & Stress Mechanisms of Stress Response Afferent Neural Stimuli Minor CNS ( Pain) Major CNS + Other Factors 1. Local Tissue Factors 2. Modifying Factors 8 Prof. M. El-ansary, Al-Azhar University Friday, October 09, 2015
Pain & Stress Stress Response Acute (Shock) Very Short (hrs) Hyperdynamic (Flow) Catabolic Hormones Anabolic Hormones Long (day- week) 9 Prof. M. El-ansary, Al-Azhar University Friday, October 09, 2015
Release of : Stress response to pain insulin, cortisol, catecholamine, and other hormons Resp. Dep Hypercoagulabilty Muscles pneumonia thrombosis or embolism spasm or atrophy urinary bladder urinary retention. High sympathetic tone Sleep deprivation ischemic H. D anxiety and depression. Dunwoody CJ, Krenzischek DA, Pasero C, Rathmell JP, Polomano RC. Assessment, physiological monitoring, and consequences of inadequately treated acute pain. Pain Manag Nurs. 2008;9:S11 S21.
Pre-emptive analgesia, Jørgen B. Dahl and Steen Møiniche, Department of Anaesthesiology, Glostrup University Hospital, Glostrup, Denmark, Correspondence to: Jørgen B. Dahl, Department of Anaesthesiology, Glostrup University Hospital Ndr. Ringvej, DK-2600 Glostrup, Denmark, Accepted November 3, 2004
Physiology of pain: Pain processing in the brain Cerebral cortex Thalamus Limbic system Hypothalamus Medulla oblongata Reticular formation Spinal cord
Physiology Touch pain Pain Nerve C-fibre A-ß-fibre
Physiology Peripheral nerve pathways do not react like telephone wires!
Pathophysiology Nerve pathways are not one-way streets! CGRP, COX2 Na-channel BK1-R
Pathophysiology peripheral and central mechanisms Massive AP influx on a spinal level Release of TNF, IL-1 NGF Intracellular molecular change Number of receptors (AMPA, NMDA, NK1) Antero- and retrograde axonal transport Expression of bradykinin receptors Neuropeptides Local effect: Na channels Cytokine Induction of COX-2 Central sensitisation Peripheral sensitisation
Pathophysiology - chronic neuropathy Central sensitisation: Touch pain Pain C-fibre A-ß-fibre WDR neurone
Pathogenesis of post-herpetic pain C-fibre degeneration: touch pain Pain C-fibre degeneration A-ß-fibre Sprouting
Pathogenesis of sympathetic pain Sympathetic nociceptive coupling Sympathetic fibre Noradrenaline NA NA NA C- Faser NA Ramer et al., 1998
Chronic postsurgical pain Chronic postsurgical pain (CPSP) 3 6 months It disrupts their quality of life 10-50%. CPSP due to: inflammatory processes initiation of neuropathic pain from peripheral nerve damage Several risk factors : psychosocial factors, sex, age, level of pre-existing pain. genetic predisposition Multimodal analgesia : use of surgical techniques that avoid nerve damage are beneficial for preventing long-term postsurgical pain Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet. 2006;367:1618 1625
Preventive Analgesia (aims and methods) To block perioperative pain To block neurochemical cascade chronic pain By blockade (NMDA-Rs) By arresting glial cells reaction By preventing the phenotypic interneurons to become pronociceptive. Katz J, McCartney CJL. Current status of preemptive analgesia.curr Opin Anaesthesiol 2002;15:435 41
Sources of perioperative pain Peripheral sensitization afferent input arising from nerve injury cut of primary afferents (e.g., retraction) Postoperative inflammation (hours weeks) Central sensitization hyperexcitability and ectopic activity in DRG hyperexcitability and ectopic activity in DHN
Factors and phases of perioperative pain Preoperative Genetic predisposition, Psychological vulnerability, Non-genetic environnemental variables (expectations, cultural, dietary, and more), preoperative noxious inputs, and pain Intraoperative Cutting, retraction, manipulation, chemical irritation by sterilizing substances and stress response Postoperative regenerating wounded structures fibrosis Katz J, Seltzer Z. Transition from acute to chronic postsurgical pain: risk factors and protective factors. Expert Rev Neurother 44-49 : 7230, 2009
Left untreated, acute pain can lead to: 1. Emotional and psychological distress 2. Potential to develop chronic pain state 3. which is much more difficult to manage
The plan for preventive analgesia Taking a thorough patient history, Including: 1. Factors such as prior responses to pain, 2. Past contact with analgesics, 3. Current medications, 4. Fears or concerns regarding future pain, 5. Any additional relevant information.
Preventive (perioperative) analgesia Time of analgesia Before, during and post-operatively Type of analgesia (multimodal) Systemic IV NSAIDs (anti Cox 1,2) & opioids NMDA receptors antagonists ketamine Anti convulsants pregabalin Local analgesics Wound infiltration Peripheral N. block Extended epidural or intrathecal analgesia Pre, intra, and post operatively Adjuvants (opioids and/or ά2 agonists ) G. anesthesia no block of stress response Lavand homme P, De Kock M, Waterloos H. Intraoperative epidural analgesia combined with ketamine provides effective preventive analgesia in patients undergoing major digestive surgery. Anesthesiology 2005;103:813 20
Møiniche S, Kehlet H, Dahl JB. A qualitative and quantitative systematic review of preemptive analgesia for postoperative pain relief: the role of timing of analgesia. Anesthesiology 41-96:725; 2002 Is There a Link Between Acute Pain and Chronic Pain?
Transition from acute to chronic pain N.injury cascade of reactions leading to the transition from acute to chronic pain destruction of In the DHNs glial cells antinociceptive inhibitory Ns activation GABAergic interneurons in the dorsal horn from being normally: antinociceptive pronociceptive interneurons. Coull JA, Beggs S, Boudreau D, Boivin D, Tsuda M, Inoue K, Gravel C, Salter MW, De Koninck Y. BDNF from microglia, causes the shift in neuronal anion gradient underlying neuropathic pain. Nature 2005;438:1017 21
Take home messages 1. Pre-emptive analgesia provides better analgesia postoperatively if applied before incision or surgery. 2. Multimodal analgesia means the use of lower doses of any one medication to be used in combination with less side effects. 3. Preventive analgesia could be used before, during or after incision and surgery. 4. Duration of treatment and effective analgesic regimens are important factors in the administration of preventive analgesia. 5. Preventive analgesia is more effective than peemptive analgesia to prevent chronic pain