DOI QR코드

DOI QR Code

Pharmacologic Management of Chronic Pain

  • Park, Hue-Jung (Department of Anesthesiology and Pain Medicine, School of Medicine, The Catholic University of Korea) ;
  • Moon, Dong-Eon (Department of Anesthesiology and Pain Medicine, School of Medicine, The Catholic University of Korea)
  • Received : 2010.05.06
  • Accepted : 2010.05.13
  • Published : 2010.06.01

Abstract

Chronic pain is a multifactorial condition with both physical and psychological symptoms, and it affects around 20% of the population in the developed world. In spite of outstanding advances in pain management over the past decades, chronic pain remains a significant problem. This article provides a mechanism- and evidence-based approach to improve the outcome for pharmacologic management of chronic pain. The usual approach to treat mild to moderate pain is to start with a nonopioid analgesic. If this is inadequate, and if there is an element of sleep deprivation, then it is reasonable to add an antidepressant with analgesic qualities. If there is a component of neuropathic pain or fibromyalgia, then a trial with one of the gabapentinoids is appropriate. If these steps are inadequate, then an opioid analgesic may be added. For moderate to severe pain, one would initiate an earlier trial of a long term opioid. Skeletal muscle relaxants and topicals may also be appropriate as single agents or in combination. Meanwhile, the steps of pharmacologic treatments for neuropathic pain include (1) certain antidepressants (tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors), calcium channel ${\alpha}2-{\delta}$ ligands (gabapentin and pregabalin) and topical lidocaine, (2) opioid analgesics and tramadol (for first-line use in selected clinical circumstances) and (3) certain other antidepressant and antiepileptic medications (topical capsaicin, mexiletine, and N-methyl-d-aspartate receptor antagonists). It is essential to have a thorough understanding about the different pain mechanisms of chronic pain and evidence-based multi-mechanistic treatment. It is also essential to increase the individualization of treatment.

Keywords

References

  1. Kroenke K, Krebs EE, Bair MJ. Pharmacotherapy of chronic pain: a synthesis of recommendations from systematic reviews. Gen Hosp Psychiatry 2009; 31: 206-19. https://doi.org/10.1016/j.genhosppsych.2008.12.006
  2. Varrassi G, Müller-Schwefe G, Pergolizzi J, Oronska A, Morlion B, Mavrocordatos P, et al. Pharmacological treatment of chronic pain - the need for CHANGE. Curr Med Res Opin 2010; 26: 1231-45. https://doi.org/10.1185/03007991003689175
  3. Treede RD, Jensen TS, Campbell JN, Cruccu G, Dostrovsky JO, Griffin JW, et al. Neuropathic pain: redefinition and a grading system for clinical research purposes. Neurology 2008; 70: 1630-5. https://doi.org/10.1212/01.wnl.0000282763.29778.59
  4. Torrance N, Smith BH, Watson MC, Bennett MI. Medication and treatment use in primary care patients with chronic pain of predominantly neuropathic origin. Fam Pract 2007; 24: 481-5. https://doi.org/10.1093/fampra/cmm042
  5. Smith BH, Torrance N, Bennett MI, Lee AJ. Health and quality of life associated with chronic pain of predominantly neuropathic origin in the community. Clin J Pain 2007; 23: 143-9. https://doi.org/10.1097/01.ajp.0000210956.31997.89
  6. Roelofs PD, Deyo RA, Koes BW, Scholten RJ, van Tulder MW. Nonsteroidal anti-inflammatory drugs for low back pain: an updated Cochrane review. Spine 2008; 33: 1766-74. https://doi.org/10.1097/BRS.0b013e31817e69d3
  7. Antman EM, Bennett JS, Daugherty A, Furberg C, Roberts H, Taubert KA. Use of nonsteroidal antiinflammatory drugs: an update for clinicians: a scientific statement from the American Heart Association. Circulation 2007; 115: 1634-42. https://doi.org/10.1161/CIRCULATIONAHA.106.181424
  8. Lee C, Straus WL, Balshaw R, Barlas S, Vogel S, Schnitzer TJ. A comparison of the efficacy and safety of nonsteroidal antiinflammatory agents versus acetaminophen in the treatment of osteoarthritis: a meta-analysis. Arthritis Rheum 2004; 51: 746-54. https://doi.org/10.1002/art.20698
  9. Towheed TE, Maxwell L, Judd MG, Catton M, Hochberg MC, Wells G. Acetaminophen for osteoarthritis. Cochrane Database Syst Rev 2006; 1: CD004257.
  10. Wegman A, van der Windt D, van Tulder M, Stalman W, de Vries T. Nonsteroidal antiinflammatory drugs or acetaminophen for osteoarthritis of the hip or knee? A systematic review of evidence and guidelines. J Rheumatol 2004; 31: 344-54.
  11. Watkins PB, Kaplowitz N, Slattery JT, Colonese CR, Colucci SV, Stewart PW, et al. Aminotransferase elevations in healthy adults receiving 4 grams of acetaminophen daily: a randomized controlled trial. JAMA 2006; 296: 87-93. https://doi.org/10.1001/jama.296.1.87
  12. Bonezzi C, Allegri M, Demartini L, Buonocore M. The pharmacological treatment of neuropathic pain. Eur J Pain Suppl 2009; 3: 85-8. https://doi.org/10.1016/j.eujps.2009.08.009
  13. McDiarmid T, Mackler L, Schneider DM. Clinical inquiries. What is the addiction risk associated with tramadol? J Fam Pract 2005; 54: 72-3.
  14. Sansone RA, Sansone LA. Tramadol: seizures, serotonin syndrome, and coadministered antidepressants. Psychiatry (Edgmont) 2009; 6: 17-21.
  15. Lynch ME. The pharmacotherapy of chronic pain. Rheum Dis Clin North Am 2008; 34: 369-85. https://doi.org/10.1016/j.rdc.2008.04.001
  16. Furlan AD, Sandoval JA, Mailis-Gagnon A, Tunks E. Opioids for chronic noncancer pain: a meta-analysis of effectiveness and side effects. CMAJ 2006; 174: 1589-94. https://doi.org/10.1503/cmaj.051528
  17. Jovey RD, Ennis J, Gardner-Nix J, Goldman B, Hays H, Lynch M, et al. Use of opioid analgesics for the treatment of chronic noncancer pain--a consensus statement and guidelines from the Canadian Pain Society, 2002. Pain Res Manag 2003; 8(Suppl A): 3A-28A. https://doi.org/10.1155/2003/436716
  18. Lynch ME, Watson CP. The pharmacotherapy of chronic pain: a review. Pain Res Manag 2006; 11: 11-38. https://doi.org/10.1155/2006/642568
  19. Lynch ME. A review of the use of methadone for the treatment of chronic noncancer pain. Pain Res Manag 2005; 10: 133-44. https://doi.org/10.1155/2005/286713
  20. Fine PG, Mahajan G, McPherson ML. Long-acting opioids and short-acting opioids: appropriate use in chronic pain management. Pain Med 2009; 10(Suppl 2): S79-88. https://doi.org/10.1111/j.1526-4637.2009.00666.x
  21. Moore RA, McQuay HJ. Prevalence of opioid adverse events in chronic non-malignant pain: systematic review of randomised trials of oral opioids. Arthritis Res Ther 2005; 7: R1046-51. https://doi.org/10.1186/ar1782
  22. Eisenberg E, McNicol E, Carr DB. Opioids for neuropathic pain. Cochrane Database Syst Rev 2006; 3: CD006146.
  23. Ballantyne JC, Mao J. Opioid therapy for chronic pain. N Engl J Med 2003; 349: 1943-53. https://doi.org/10.1056/NEJMra025411
  24. Daniell HW. Hypogonadism in men consuming sustainedaction oral opioids. J Pain 2002; 3: 377-84. https://doi.org/10.1054/jpai.2002.126790
  25. Daniell HW. Opioid endocrinopathy in women consuming prescribed sustained-action opioids for control of nonmalignant pain. J Pain 2008; 9: 28-36.
  26. Hojsted J, Sjogren P. An update on the role of opioids in the management of chronic pain of nonmalignant origin. Curr Opin Anaesthesiol 2007; 20: 451-5. https://doi.org/10.1097/ACO.0b013e3282ef6b18
  27. Fishbain DA, Cutler RB, Rosomoff HL, Rosomoff RS. Are opioid-dependent/tolerant patients impaired in driving-related skills? A structured evidence-based review. J Pain Symptom Manage 2003; 25: 559-77. https://doi.org/10.1016/S0885-3924(03)00176-3
  28. McQuay HJ, Tramér M, Nye BA, Carroll D, Wiffen PJ, Moore RA. A systematic review of antidepressants in neuropathic pain. Pain 1996; 68: 217-27. https://doi.org/10.1016/S0304-3959(96)03140-5
  29. Collins SL, Moore RA, McQuay HJ, Wiffen P. Antidepressants and anticonvulsants for diabetic neuropathy and postherpetic neuralgia: a quantitative systematic review. J Pain Symptom Manage 2000; 20: 449-58. https://doi.org/10.1016/S0885-3924(00)00218-9
  30. Mendell JR, Sahenk Z. Clinical practice. Painful sensory neuropathy. N Engl J Med 2003; 348: 1243-55. https://doi.org/10.1056/NEJMcp022282
  31. Jung AC, Staiger T, Sullivan M. The efficacy of selective serotonin reuptake inhibitors for the management of chronic pain. J Gen Intern Med 1997; 12: 384-9. https://doi.org/10.1007/s11606-006-5088-3
  32. Goldstein DJ, Lu Y, Detke MJ, Lee TC, Iyengar S. Duloxetine vs. placebo in patients with painful diabetic neuropathy. Pain 2005; 116: 109-18. https://doi.org/10.1016/j.pain.2005.03.029
  33. Raskin J, Pritchett YL, Wang F, D'Souza DN, Waninger AL, Iyengar S, et al. A double-blind, randomized multicenter trial comparing duloxetine with placebo in the management of diabetic peripheral neuropathic pain. Pain Med 2005; 6: 346-56. https://doi.org/10.1111/j.1526-4637.2005.00061.x
  34. Wernicke JF, Pritchett YL, D'Souza DN, Waninger A, Tran P, Iyengar S, et al. A randomized controlled trial of duloxetine in diabetic peripheral neuropathic pain. Neurology 2006; 67:1411-20. https://doi.org/10.1212/01.wnl.0000240225.04000.1a
  35. Perahia DG, Pritchett YL, Desaiah D, Raskin J. Efficacy of duloxetine in painful symptoms: an analgesic or antidepressant effect? Int Clin Psychopharmacol 2006; 21: 311-7. https://doi.org/10.1097/01.yic.0000224782.83287.3c
  36. Arnold LM, Lu Y, Crofford LJ, Wohlreich M, Detke MJ, Iyengar S, et al. A double-blind, multicenter trial comparing duloxetine with placebo in the treatment of fibromyalgia patients with or without major depressive disorder. Arthritis Rheum 2004; 50: 2974-84. https://doi.org/10.1002/art.20485
  37. Arnold LM, Rosen A, Pritchett YL, D'Souza DN, Goldstein DJ, Iyengar S, et al. A randomized, double-blind, placebocontrolled trial of duloxetine in the treatment of women with fibromyalgia with or without major depressive disorder. Pain 2005; 119: 5-15. https://doi.org/10.1016/j.pain.2005.06.031
  38. Arnold LM, Pritchett YL, D'Souza DN, Kajdasz DK, Iyengar S, Wernicke JF. Duloxetine for the treatment of fibromyalgia in women: pooled results from two randomized, placebocontrolled clinical trials. J Womens Health (Larchmt) 2007; 16: 1145-56. https://doi.org/10.1089/jwh.2006.0213
  39. Rowbotham M, Goli V, Kunz NR, Lei D. Venlafaxine extended release in the treatment of painful diabetic neuropathy: a double-blind, placebo-controlled study. Pain 2004; 110: 697-706. https://doi.org/10.1016/j.pain.2004.05.010
  40. Grothe DR, Scheckner B, Albano D. Treatment of pain syndromes with venlafaxine. Pharmacotherapy 2004; 24: 621-9. https://doi.org/10.1592/phco.24.6.621.34748
  41. Spielmans GI. Duloxetine does not relieve painful physical symptoms in depression: a meta-analysis. Psychother Psychosom 2008; 77: 12-6. https://doi.org/10.1159/000110055
  42. Krebs EE, Gaynes BN, Gartlehner G, Hansen RA, Thieda P, Morgan LC, et al. Treating the physical symptoms of depression with second-generation antidepressants: a systematic review and metaanalysis. Psychosomatics 2008; 49: 191-8. https://doi.org/10.1176/appi.psy.49.3.191
  43. Brecht S, Courtecuisse C, Debieuvre C, Croenlein J, Desaiah D, Raskin J, et al. Efficacy and safety of duloxetine 60 mg once daily in the treatment of pain in patients with major depressive disorder and at least moderate pain of unknown etiology: a randomized controlled trial. J Clin Psychiatry 2007; 68: 1707-16. https://doi.org/10.4088/JCP.v68n1110
  44. Carlton SM, Zhou S. Attenuation of formalin-induced nociceptive behaviors following local peripheral injection of gabapentin. Pain 1998; 76: 201-7. https://doi.org/10.1016/S0304-3959(98)00043-8
  45. Field MJ, Holloman EF, McCleary S, Hughes J, Singh L. Evaluation of gabapentin and S-(+)-3-isobutylgaba in a rat model of postoperative pain. J Pharmacol Exp Ther 1997; 282: 1242-6.
  46. Chen SR, Xu Z, Pan HL. Stereospecific effect of pregabalin on ectopic afferent discharges and neuropathic pain induced by sciatic nerve ligation in rats. Anesthesiology 2001; 95: 1473-9. https://doi.org/10.1097/00000542-200112000-00029
  47. McQuay H, Carroll D, Jadad AR, Wiffen P, Moore A. Anticonvulsant drugs for management of pain: a systematic review. BMJ 1995; 311: 1047-52. https://doi.org/10.1136/bmj.311.7012.1047
  48. van Tulder MW, Touray T, Furlan AD, Solway S, Bouter LM. Cochrane Back Review Group. Muscle relaxants for nonspecific low back pain: a systematic review within the framework of the cochrane collaboration. Spine 2003; 28: 1978-92. https://doi.org/10.1097/01.BRS.0000090503.38830.AD
  49. Chong MS, Hester J. Diabetic painful neuropathy: current and future treatment options. Drugs 2007; 67: 569-85. https://doi.org/10.2165/00003495-200767040-00006
  50. Mason L, Moore RA, Derry S, Edwards JE, McQuay HJ. Systematic review of topical capsaicin for the treatment of chronic pain. BMJ 2004; 328: 991. https://doi.org/10.1136/bmj.38042.506748.EE
  51. Mason L, Moore RA, Edwards JE, McQuay HJ, Derry S, Wiffen PJ. Systematic review of efficacy of topical rubefacients containing salicylates for the treatment of acute and chronic pain. BMJ 2004; 328: 995. https://doi.org/10.1136/bmj.38040.607141.EE
  52. Underwood M, Ashby D, Cross P, Hennessy E, Letley L, Martin J, et al. Advice to use topical or oral ibuprofen for chronic knee pain in older people: randomised controlled trial and patient preference study. BMJ 2008; 336: 138-42. https://doi.org/10.1136/bmj.39399.656331.25
  53. Nandi R, Beacham D, Middleton J, Koltzenburg M, Howard RF, Fitzgerald M. The functional expression of mu opioid receptors on sensory neurons is developmentally regulated; morphine analgesia is less selective in the neonate. Pain 2004; 111: 38-50. https://doi.org/10.1016/j.pain.2004.05.025
  54. Lonnqvist PA, Morton NS. Postoperative analgesia in infants and children. Br J Anaesth 2005; 95: 59-68. https://doi.org/10.1093/bja/aei065
  55. Bhatt DL, Scheiman J, Abraham NS, Antman EM, Chan FK, Furberg CD, et al. ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. Circulation 2008; 118: 1894-909. https://doi.org/10.1161/CIRCULATIONAHA.108.191087
  56. Barkin RL, Barkin SJ, Barkin DS. Pharmacotherapeutic management of pain with a focus directed at the geriatric patient. Rheum Dis Clin North Am 2007; 33: 1-31. https://doi.org/10.1016/j.rdc.2006.12.001
  57. Barkin RL, Sable KS. Caution recommended for prescribing and administering COX-1/COX-2 and COX-2 specific NSAIDs. P T 2000; 25: 196-202.
  58. Innes GD, Zed PJ. Basic pharmacology and advances in emergency medicine. Emerg Med Clin North Am 2005; 23: 433-65. https://doi.org/10.1016/j.emc.2004.12.010
  59. Murphy EJ. Acute pain management pharmacology for the patient with concurrent renal or hepatic disease. Anaesth Intensive Care 2005; 33: 311-22.
  60. Davies G, Kingswood C, Street M. Pharmacokinetics of opioids in renal dysfunction. Clin Pharmacokinet 1996; 31: 410-22. https://doi.org/10.2165/00003088-199631060-00002
  61. Stern SS, Ponticello MN. Current concepts in pain management: pharmacologic options for the pediatric, geriatric, hepatic and renal failure patient. Clin Podiatr Med Surg 2008; 25: 381-407. https://doi.org/10.1016/j.cpm.2008.02.013
  62. O'Connor AB, Dworkin RH. Treatment of neuropathic pain: an overview of recent guidelines. Am J Med 2009; 122(Suppl 10): S22-32.

Cited by

  1. Current pharmacological management of chronic pain vol.53, pp.9, 2010, https://doi.org/10.5124/jkma.2010.53.9.815
  2. Glycosylation of Capsaicin Derivatives and Phenylpropanoid Derivatives Using Cultured Plant Cells vol.4, pp.1178-6264, 2011, https://doi.org/10.4137/BCI.S6682
  3. Cannabinoids for the treatment of neuropathic pain: are they safe and effective? vol.6, pp.2, 2011, https://doi.org/10.2217/fnl.11.6
  4. Antinociceptive activities of some triazole and pyrazoline moieties-bearing compounds vol.21, pp.7, 2012, https://doi.org/10.1007/s00044-011-9619-z
  5. Chronic Pain and Its Determinants: A Population-based Study in Southern Iran vol.25, pp.4, 2012, https://doi.org/10.3344/kjp.2012.25.4.245
  6. Acute Systemic Infusion of Bupropion Decrease Formalin Induced Pain Behavior in Rat vol.27, pp.2, 2014, https://doi.org/10.3344/kjp.2014.27.2.118
  7. Comparison of Analgesic Effects of Remifentanil and Fentanyl NCA after Pediatric Cardiac Surgery vol.27, pp.4, 2014, https://doi.org/10.3109/08941939.2013.879968
  8. Korean Version of the painDETECT Questionnaire: A Study for Cultural Adaptation and Validation vol.17, pp.4, 2017, https://doi.org/10.1111/papr.12472
  9. Chronic Pain and Cognitive Behavioral Therapy vol.38, pp.5, 2016, https://doi.org/10.1177/0193945915615869
  10. Guidelines for prescribing opioids for chronic non-cancer pain in Korea vol.30, pp.1, 2017, https://doi.org/10.3344/kjp.2017.30.1.18
  11. Low doses of amitriptyline, pregabalin, and gabapentin are preferred for management of neuropathic pain in India: is there a need for revisiting dosing recommendations? vol.30, pp.3, 2017, https://doi.org/10.3344/kjp.2017.30.3.183
  12. A Clinical Study of Electroacupuncture and Auricular Acupuncture for Abdominal Pain Relief in Patients with Pancreatitis: A Pilot Study vol.34, pp.1, 2017, https://doi.org/10.14406/acu.2017.005
  13. Tapentadol in neuropathic pain cancer patients: a prospective open label study vol.38, pp.10, 2017, https://doi.org/10.1007/s10072-017-3035-1
  14. The Effectiveness and Safety of Topical Capsaicin in Postherpetic Neuralgia: A Systematic Review and Meta-analysis vol.7, pp.1663-9812, 2017, https://doi.org/10.3389/fphar.2016.00538
  15. Management of chronic neuropathic pain with single and compounded topical analgesics vol.7, pp.6, 2017, https://doi.org/10.2217/pmt-2017-0020
  16. Different electrophysiological effects of the levo- and dextro-rotatory isomers of mexiletine in isolated rabbit cardiac muscle vol.95, pp.7, 2017, https://doi.org/10.1139/cjpp-2016-0599
  17. Anti-Allodynic Effects of Levodopa in Neuropathic Rats vol.54, pp.2, 2013, https://doi.org/10.3349/ymj.2013.54.2.330
  18. Double blind randomized control trial to evaluate the efficacy of ketoprofen patch to attenuate pain during venous cannulation vol.31, pp.1, 2018, https://doi.org/10.3344/kjp.2018.31.1.39
  19. Therapeutic alternatives in painful diabetic neuropathy: a meta-analysis of randomized controlled trials vol.31, pp.4, 2018, https://doi.org/10.3344/kjp.2018.31.4.253
  20. Analgesic Efficacy and Safety of Prolonged-Release Oxycodone/Naloxone in Korean Patients with Chronic Pain from Spinal Disorders vol.10, pp.1, 2018, https://doi.org/10.4055/cios.2018.10.1.33
  21. Pregnancy in Woman with Spinal Cord Stimulator for Complex Regional Pain Syndrome: A Case Report and Review of the Literature vol.23, pp.4, 2010, https://doi.org/10.3344/kjp.2010.23.4.266
  22. Peroxisome proliferator-activated receptor agonists modulate neuropathic pain: a link to chemokines? vol.8, pp.None, 2010, https://doi.org/10.3389/fncel.2014.00238
  23. Pain management in cryoglobulinaemic syndrome vol.29, pp.1, 2015, https://doi.org/10.1016/j.berh.2015.04.033
  24. Low Level Laser Therapy Versus Pharmacotherapy in Improving Myofascial Pain Disorder Syndrome vol.7, pp.1, 2010, https://doi.org/10.15171/jlms.2016.10
  25. Ultrasound-Guided Nerve Block with Botulinum Toxin Type A for Intractable Neuropathic Pain vol.8, pp.1, 2016, https://doi.org/10.3390/toxins8010018
  26. An Overview of Pharmacologic Management of Chronic Pain vol.100, pp.1, 2010, https://doi.org/10.1016/j.mcna.2015.08.006
  27. Opioids Resistance in Chronic Pain Management vol.15, pp.3, 2017, https://doi.org/10.2174/1570159x14666161101092822
  28. Transdermal Ketoprofen Patch in Comparison to Eutectic Mixture of Local Anesthetic Cream and Subcutaneous Lidocaine to Control Pain Due to Venous Cannulation vol.12, pp.4, 2010, https://doi.org/10.4103/aer.aer_166_18
  29. PREVALENCE OF DEPRESSIVE DISORDER AND ITS TREATMENT AMONG PATIENTS WITH CHRONIC PAIN- A CROSS SECTIONAL STUDY vol.6, pp.12, 2010, https://doi.org/10.18410/jebmh/2019/205
  30. Bazı piperazin alkanol türevlerinin antinosiseptif etkinlikleri vol.44, pp.3, 2010, https://doi.org/10.17826/cumj.490690
  31. Associations between chronic pain, analgesic use and physical therapy among adults living with HIV in Atlanta, Georgia: a retrospective cohort study vol.32, pp.1, 2010, https://doi.org/10.1080/09540121.2019.1661950
  32. Medicolegal Consideration to Prevent Medical Malpractice Regarding Opioid Administration: An Analysis of Judicial Opinion in South Korea vol.13, pp.None, 2010, https://doi.org/10.2147/jpr.s256759
  33. Non-Opioid Perioperative Pain Strategies for the Clinician: A Narrative Review vol.9, pp.1, 2010, https://doi.org/10.1007/s40122-019-00146-3
  34. A Glra3 phosphodeficient mouse mutant establishes the critical role of protein kinase A-dependent phosphorylation and inhibition of glycine receptors in spinal inflammatory hyperalgesia vol.162, pp.9, 2021, https://doi.org/10.1097/j.pain.0000000000002236
  35. Serotonin syndrome in a patient with chronic pain taking analgesic drugs mistaken for psychogenic nonepileptic seizure: a case report vol.38, pp.4, 2010, https://doi.org/10.12701/yujm.2021.00948