Chronic postoperative pain syndrome: where we are in understanding the genetic risk factors, mechanisms and pharmacotherapy?

Kolesnikov Yu.A.

doi:https://doi.org/10.17116/pain20211903153

Close metadata

Recommended articles:

Reflexotherapy as an effective component of postoperative pain relief. Russian Journal of Pain. 2024;(4):41-45

Purinergic mechanisms of pain relief: fashionable topic or real opportunity to improve the quality of analgesic therapy?. Russian Journal of Pain. 2024;(4):86-95

Chronic postoperative pain in cardiac surgery: analysis of quantitative sensory testing and pain history data. Russian Journal of Pain. 2025;(1):16-23

Neuropathic pain in chronic inflammatory demyelinating polyneuropathies: analysis of 64 cases. Russian Journal of Pain. 2025;(2):45-53

Transitional pain service in surgery as an optimal strategy for the treatment and prevention of chronic postoperative pain. Pirogov Russian Journal of Surgery. 2024;(11):60-64

Psychoemotional health of patients with neuropathic pelvic pain under combined magnetic therapy. Regenerative Biotechnologies, Preventive, Digital and Predictive Medicine. 2025;(1):12-18

Modern and promising therapies for postherpetic neuralgia. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(4):27-34

Potential of animal-derived neuropeptides in complex therapy of diabetic neuropathy in patients with type 2 diabetes mellitus. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(4):83-87

Pharmacological correction of burning eye syndrome. Russian Annals of Ophthalmology. 2025;(2):51-58

Cocarnit in complex therapy of diabetic peripheral polyneuropathy. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(7):73-81

Abstract:

This review is devoted to analysis of modern scientific data on chronic postoperative pain syndrome. According to the authors, the incidence of chronic pain is still high and has changed little since the first publication in the late 1990s. Nevertheless, significant advances have been made in understanding the mechanisms of chronic pain, risk factors and genetic predisposition to chronic pain. Preventive methods are not always effective for this syndrome, and cannot be introduced into routine medical practice. Pharmacotherapy of chronic postoperative pain is widely used. Unfortunately, effectiveness and safety of these combinations do not meet modern requirements for analgesics. Application of local analgesics with different mechanisms of action is one of the alternative methods of treatment that will reduce the dose of systemic drugs. In this context, methods of treatment aimed at peripheral targets look perspective.

Keywords:

chronic postoperative pain

neuropathic pain

pain genetics

local analgesics

Authors:

Kolesnikov Yu.A.

Medical Center «Medicum»

Received:

10.05.2021

Accepted:

17.05.2021

Close metadata

References:

Schug SA, Lavand’homme P, Barke A, Korwisi B, Rief W, Treede, RD. The IASP classification of chronic pain for ICD-11: chronic postsurgical or posttraumatic pain. Pain. 2019;160(1):45-52. https://doi.org/10.1097/j.pain.0000000000001413
Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet. 2006;367(9522):1618-1625. https://doi.org/10.1016/S0140-6736(06)68700-X
Crombie IK, Davies HT, Macrae WA: Cut and thrust: antecedent surgery and trauma among patients attending a chronic pain clinic. Pain. 1998;76(1-2):167-171. PMID: 9696470.
Macrae WA, Davies HT. Chronic postsurgical pain. In: Epidemiology of pain. Edited by Crombie IK, Linton S, Croft P, Von Korff M, LeResche L. Seattle: IASP Press; 1999;125-142.
Macrae WA. Chronic post-surgical pain: 10 years on. Br J Anaesth. 2008; 101(1):77-86. https://doi.org/10.1093/bja/aen099
Werner MU, Kongsgaard UE. Defining persistent post-surgical pain: is an update required? Br J Anaesth. 2014;113(1):1-4. https://doi.org/10.1093/bja/aeu012
Correll D. Chronic postoperative pain: recent findings in understanding and management. Version 1. F1000Res. 2017;6:1054. https://doi.org/10.12688/f1000research.11101.1
Richebé, P, Capdever X, Rivat C. Persistent Postsurgical Pain: Pathophysiology and Preventative Pharmacologic Considerations. Anaesthesiology. 2018;129:590-607. https://doi.org/10.1097/ALN.0000000000002238
Fletcher D, Stamer UM, Pogatzki-Zahn E, Zaslansky R, Tanase NV, Perruchoud C, Kranke P, Komann M, Lehman T, Meissner W. Chronic postsurgical pain in Europe. An observational study. Eur J Anaesthesiol. 2015;32(10):725-734. https://doi.org/10.1097/EJA.0000000000000319
Bayman EO, Brennan TJ. Incidence and severity of chronic pain at 3 and 6 months after thoracotomy: meta-analysis. J Pain. 2014;15(9):887-897. https://doi.org/10.1016/j.jpain.2014.06.005
Niraj G, Kelkar A, Kaushik V, Tang Y, Fleet D, Tait F. Audit of postoperative pain management after open thoracotomy and the incidence of chronic postthoracotomy pain in more than 500 patients at a tertiary center. J Clin Anesth. 2017;36(4):174-177. https://doi.org/10.1016/j.jclinane.2016.10.011
Hetmann F, Kongsgaard UE, Sandvik L, Schou-Bredal I. Prevalence and predictors of persistent post-surgical pain 12 months after thoracotomy. Acta Anaesthesiol Scand. 2015;59(6):740-748. https://doi.org/10.1111/aas.12532
Wildgaard K, Ringsted TK, Hansen HJ, Petersen RH, Kehlet H. Persistent postsurgical pain after video-assisted thoracic surgery — an observational study. Acta Anaesthesiol Scand. 2016;60(5):650-658. https://doi.org/10.1111/aas.12681
Jeppesen M, Tolstrup MB, Gögenur I. Chronic Pain, Quality of Life, and Functional Impairment After Surgery Due to Small Bowel Obstruction. World J Surg. 2016;40(9):2091-2097. https://doi.org/10.1007/s00268-016-3616-9
Joris JL, Georges MJ, Medjahed K, Ledoux D, Damilot G, Ramquet CC. Prevalence, characteristics and risk factors of chronic postsurgical pain after laparoscopic colorectal surgery: Retrospective analysis. Eur J Anaesthesiol. 2015;32(10):712-717. https://doi.org/10.1097/EJA.0000000000000268
Langeveld HR, Klitsie P, Smedinga H, et al. Prognostic value of age for chronic postoperative inguinal pain. Hernia. 2015;19(4):549-555. https://doi.org/10.1007/s10029-014-1282-0
Petersen KK, Arendt-Nielsen L, Simonsen O. Presurgical assessment of temporal summation of pain predicts the development of chronic postoperative pain 12 months after total knee replacement. Pain. 2015;156(1):55-61. https://doi.org/10.1016/j.pain.0000000000000022
Hinrichs-Rocker A, Schulz K, Järvinen I, Lefering R, Simanski C, Neugebauer EA. Psychosocial predictors and correlates for chronic post-surgical pain (CPSP): A systematic review. Eur J Pain. 2009;13:719-730. https://doi.org/10.1016/j.ejpain.2008.07.015
Andersen KG, Duriaud HM, Jensen HE. Predictive factors for the development of persistent pain after breast cancer surgery. Pain. 2015;156(12):2413-2422. https://doi.org/10.1097/j.pain.0000000000000298
Rawal N. Current issues in postoperative pain management. European Journal of Anaesthesiology. 2016;33(3):160-171. https://doi.org/10.1097/EJA.0000000000000366
Wu C, Boustany L, Liang H, Brennan TJ. Nerve growth factor expression after plantar incision in the rat. Anaesthesiology. 2007;107:128-135. https://doi.org/10.1097/01.anes.0000267512.08619.bd
Ji RR, Samad TA, Jin SX, Schmoll R, Woolf CJ. p38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia. Neuron. 2002;36:57-68. https://doi.org/10.1016/s0896-6273(02)00908-x
Sahbaie P, Shi X, Guo TZ, Qiao Y, Yeomans DC, Kingery WS, Clark JD. Role of substance P signaling in enhanced nociceptive sensitization and local cytokine production after incision. Pain. 2009;145:341-349. https://doi.org/10.1016/j.pain.2009.06.037
Toth C. Peripheral and Central sensitization. In: Neuropathic Pain: Causes, Management, and Understanding. Toth C., Moulin D.E., eds. Cambridge University Press; 2013;51-64.
Ji RR, Kohno T, Moore KA, Woolf CJ: Central sensitization and LTP: Do pain and memory share similar mechanisms? Trends Neurosci. 2003;26:696-705. https://doi.org/10.1016/j.tins.2003.09.017
Pogatzki-Zahn EM, Segelcke D, Schug SA: Postoperative pain-from mechanisms to treatment. Pain Rep. 2017;2:e588. https://doi.org/10.1097/PR9.0000000000000588
Asiedu MN, Tillu DV, Melemedjian OK, Shy A, Sanoja R, Bodell B, Ghosh S, Porreca F, Price TJ: Spinal protein kinase Mζ underlies the maintenance mechanism of persistent nociceptive sensitization. J Neurosci. 2011;31: 6646-6653. https://doi.org/10.1523/JNEUROSCI.6286-10.2011
Sun Y, Sahbaie P, Liang D, Li W, Shi X, Kingery P, Clark JD. DNA methylation modulates nociceptive sensitization after incision. PLoS One. 2015; 10:e0142046. https://doi.org/10.1371/journal.pone.0142046
Sun Y, Sahbaie P, Liang DY, Li WW, Li XQ, Shi XY, Clark JD. Epigenetic regulation of spinal CXCR2 signaling in incisional hypersensitivity in mice. Anesthesiology. 2013;119:1198-11208. https://doi.org/10.1097/ALN.0b013e31829ce340
Ladha KS, Patorno E, Liu J, Bateman BT. Impact of perioperative epidural placement on postdischarge opioid use in patients undergoing abdominal surgery. Anesthesiology. 2016;124:396-403. https://doi.org/10.1097/ALN.0000000000000952
Capdevila X, Moulard S, Plasse C, Peshaud JL, Molinari N, Dadure C, Bringuier S. Effectiveness of epidural analgesia, continuous surgical site analgesia, and patient-controlled analgesic morphine for postoperative pain management and hyperalgesia, rehabilitation, and health-related quality of life after open nephrectomy: A prospective, randomized, controlled study. Anesth Analg. 2017;124:336-345. https://doi.org/10.1213/ANE.0000000000001688
Dai F, Belfer I, Schwartz CE, Banco R, Martha JF, Tighioughart H, Tromanhauser SG, Jenis LG, Kim DH. Association of catechol-O-methyltransferase genetic variants with outcome in patients undergoing surgical treatment for lumbar degenerative disc disease. Spine J. 2010;10(11):949-957. https://doi.org/10.1016/j.spinee.2010.07.387
Tegeder I, Costigan M, Griffin RS, Abele A, Belfer I. GTP cyclohydrolase and tetrahydrobiopterin regulate pain sensitivity and persistence. Nat Med. 2006;2:1269-1277. https://doi.org/10.1038/nm1490
Zubieta JK, Heitzeg MM, Smith Y, Bueller J. COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain stressor. Science. 2003;299(5610):1240-1243. https://doi.org/10.1126/science.1078546
Nackley AG, Tan KS, Fecho K, Flood P, Diatchenko L, Maixner W. Catechol-O-methyltransferase inhibition increases pain sensitivity through activation of both beta2- and beta3-adrenergic receptors. Pain. 2007;128(3):199-208. https://doi.org/10.1016/j.pain.2006.09.022
Kolesnikov YA, Gabovits B, Levin A, Veske A, Qin L, Dai F, Belfer I. Chronic pain after lower abdominal surgery: do catechol-O-methyl transferase/opioid receptor μ-1 polymorphisms contribute? Mol Pain. 2013;9:19. https://doi.org/10.1186/1744-8069-9-19
Nasser A, Bjerrum OJ, Heegaard AM, Møller AT, Larsen M, Dalbøge LS, Dupont E, Jensen TS, Møller LB. Impaired behavioural pain responses in hph-1 mice with inherited deficiency in GTP cyclohydrolase 1 in models of inflammatory pain. Mol Pain. 2013;19(9):5. https://doi.org/10.1186/1744-8069-9-5
Kolesnikov Y, Gabovits B, Levin A, Voiko E, Veske A. Combined catechol-O-methyltransferase and mu-opioid receptor gene polymorphisms affect morphine postoperative analgesia and central side effects. Anesth Analg. 2011;112(2):448-453. https://doi.org/10.1213/ANE.0b013e318202cc8d
Gabovich B.E., Veske A., Dai F., Kolesnikov Yu.A. Association of genetic polymorphism of guanosintriphosphate of cyclohydrolases and catechol-O-methyltransferase with the frequency of the appearance of chronic pain after surgery. Messenger of ANESTHESIOLOGY AND RESUSCITATION. 2019; 16(5):5-11. https://doi.org/10.21292/2078-5658-2019-16-5-5-11
Campbell CM, Edwards RR, Carmona C, Uhart M, Wand G, Carteret A, Kim YK, Frost J, Campbell JN. Polymorphisms in the GTP cyclohydrolase gene (GCH1) are associated with ratings of capsaicin pain. Pain. 2009; 141:114-118. https://doi.org/10.1016/j.pain.2008.10.023
Kim H., Dionne R A. Lack of influence of GTP cyclohydrolase gene (GCH1) variations on pain sensitivity in humans. Mol Pain. 2007;7(3):6. https://doi.org/10.1186/1744-8069-3-6
Tian Y, Med B, Med M, Liu, B, Eng M. Jia M, Lichtner P. Targeted Genotyping Identifies Susceptibility Locus in Brain-derived Neurotrophic Factor Gene for Chronic Postsurgical Pain. Anesthesiology. 2018;128:587-597. https://doi.org/10.1097/ALN.0000000000001977
Thapa P, Euasobhon P. Chronic postsurgical pain: current evidence for prevention and management. Korean J Pain. 2018;31(3):155-173. https://doi.org/10.3344/kjp.2018.31.3.155
Nicolaou A, Nicholson B, Hans G, Brasseur L. Outcome predictors for treatment success with 5% lidocaine medicated plaster in low back pain with neuropathic components and neuropathic pain after surgical and nonsurgical trauma. J Pain Res. 2011;4:25-38. https://doi.org/10.2147/JPR.S15534
Lynch ME, Clark AJ, Sawynok J, Sullivan MJ. Topical amitriptyline and ketamine in neuropathic pain syndromes: an open-label study. J Pain. 2005; 6:644-649. https://doi.org/10.1016/j.jpain.2005.04.008
Glantz L, Godovic G, Lekar M, Kramer M, Eidelman LA Efficacy of transdermal nitroglycerin combined with etodolac for the treatment of chronic post-thoracotomy pain: an open-label prospective clinical trial. J Pain Symptom Manage. 2004;27(3):277-281. https://doi.org/10.1016/j.jpainsymman.2003.06.009
Larsen IM, Drewes A, Olesen AE. The Effect of a Combination of Diclofenac and Methadone Applied as Gel in a Human Experimental Pain Model — A Randomized, Placebo-controlled Trial. Basic Clin Pharmacol Toxicol. 2018;123(2):188-194. https://doi.org/10.1111/bcpt.12993