Korean J Pain.  2020 Apr;33(2):108-120. 10.3344/kjp.2020.33.2.108.

All about pain pharmacology: what pain physicians should know

Affiliations
  • 1Department of Anesthesia and Pain Medicine, School of Medicine, Pusan National University, Yangsan, Korea
  • 2Department of Pain Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Abstract

From the perspective of the definition of pain, pain can be divided into emotional and sensory components, which originate from potential and actual tissue damage, respectively. The pharmacologic treatment of the emotional pain component includes antianxiety drugs, antidepressants, and antipsychotics. The anti-anxiety drugs have anti-anxious, sedative, and somnolent effects. The antipsychotics are effective in patients with positive symptoms of psychosis. On the other hand, the sensory pain component can be divided into nociceptive and neuropathic pain. Non-steroidal anti-inflammatory drugs (NSAIDs) and opioids are usually applied for somatic and visceral nociceptive pain, respectively; anticonvulsants and antidepressants are administered for the treatment of neuropathic pain with positive and negative symptoms, respectively. The NSAIDs, which inhibit the cyclo-oxygenase pathway, exhibit anti-inflammatory, antipyretic, and analgesic effects; however, they have a therapeutic ceiling. The adverse reactions (ADRs) of the NSAIDs include gastrointestinal problems, generalized edema, and increased bleeding tendency. The opioids, which bind to the opioid receptors, present an analgesic effect only, without anti-inflammatory, antipyretic, or ceiling effects. The ADRs of the opioids start from itching and nausea/vomiting to cardiovascular and respiratory depression, as well as constipation. The anticonvulsants include carbamazepine, related to sodium channel blockade, and gabapentin and pregabalin, related to calcium blockade. The antidepressants show their analgesic actions mainly through inhibiting the reuptake of serotonin or norepinephrine. Most drugs, except NSAIDs, need an updose titration period. The principle of polypharmacy for analgesia in case of mixed components of pain is increasing therapeutic effects while reducing ADRs, based on the origin of the pain.

Keyword

Analgesics; Anticonvulsants; Antidepressive Agents; Anti-Inflammatory Agents, Non-Steroidal; Carbamazepine; Gabapentin; Neuralgia; Nociceptive Pain; Opioids; Polypharmacy; Pregabalin; Serotonin

Cited by  4 articles

Topical agents: a thoughtful choice for multimodal analgesia
Eunjoo Choi, Francis Sahngun Nahm, Woong Ki Han, Pyung-Bok Lee, Jihun Jo
Korean J Anesthesiol. 2020;73(5):384-393.    doi: 10.4097/kja.20357.

Mirogabalin: could it be the next generation gabapentin or pregabalin?
Jae-Yeon Kim, Salahadin Abdi, Billy Huh, Kyung-Hoon Kim
Korean J Pain. 2021;34(1):4-18.    doi: 10.3344/kjp.2021.34.1.4.

Timing of musculoskeletal steroid injections in pain practice during Coronavirus disease 2019 (COVID-19) vaccine administration
Kyung-Hoon Kim
Korean J Pain. 2022;35(1):1-3.    doi: 10.3344/kjp.2022.35.1.1.

Prevention, diagnosis, and treatment of opioid use disorder under the supervision of opioid stewardship programs: it’s time to act now
Eun-Ji Kim, Eun-Jung Hwang, Yeong-Min Yoo, Kyung-Hoon Kim
Korean J Pain. 2022;35(4):361-382.    doi: 10.3344/kjp.2022.35.4.361.


Reference

1. Merskey H, Albe Fessard D, Bonica JJ, Carmon A, Dubner R, Kerr FWL, et al. 1979; Pain terms: a list with definitions and notes on usage. Recommended by the IASP Subcommittee on Taxonomy. Pain. 6:249–52. PMID: 460932.
2. Jensen TS, Baron R. 2003; Translation of symptoms and signs into mechanisms in neuropathic pain. Pain. 102:1–8. DOI: 10.1016/s0304-3959(03)00006-x. PMID: 12620591.
Article
3. Baron R, Maier C, Attal N, Binder A, Bouhassira D, Cruccu G, et al. 2017; Peripheral neuropathic pain: a mechanism-related organizing principle based on sensory profiles. Pain. 158:261–72. DOI: 10.1097/j.pain.0000000000000753. PMID: 27893485. PMCID: PMC5266425.
Article
4. Attal N, Fermanian C, Fermanian J, Lanteri-Minet M, Alchaar H, Bouhassira D. 2008; Neuropathic pain: are there distinct subtypes depending on the aetiology or anatomical lesion? Pain. 138:343–53. DOI: 10.1016/j.pain.2008.01.006. PMID: 18289791.
Article
5. Bouhassira D, Attal N, Fermanian J, Alchaar H, Gautron M, Masquelier E, et al. 2004; Development and validation of the neuropathic pain symptom inventory. Pain. 108:248–57. DOI: 10.1016/j.pain.2003.12.024. PMID: 15030944.
Article
6. Loeser JD, Treede RD. 2008; The Kyoto protocol of IASP basic pain terminology. Pain. 137:473–7. DOI: 10.1016/j.pain.2008.04.025. PMID: 18583048.
7. Kallakuri S, Singh A, Chen C, Cavanaugh JM. 2004; Demonstration of substance P, calcitonin gene-related peptide, and protein gene product 9.5 containing nerve fibers in human cervical facet joint capsules. Spine (Phila Pa 1976). 29:1182–6. DOI: 10.1097/00007632-200406010-00005. PMID: 15167655.
Article
8. Park SC, Kim KH. 2012; Effect of adding cervical facet joint injections in a multimodal treatment program for long-standing cervical myofascial pain syndrome with referral pain patterns of cervical facet joint syndrome. J Anesth. 26:738–45. DOI: 10.1007/s00540-012-1404-8. PMID: 22648287.
Article
9. Kim TK, Kim KH, Kim CH, Shin SW, Kwon JY, Kim HK, et al. 2005; Percutaneous vertebroplasty and facet joint block. J Korean Med Sci. 20:1023–8. DOI: 10.3346/jkms.2005.20.6.1023. PMID: 16361816. PMCID: PMC2779303.
Article
10. Kim KH, Choi SH, Kim TK, Shin SW, Kim CH, Kim JI. 2005; Cervical facet joint injections in the neck and shoulder pain. J Korean Med Sci. 20:659–62. DOI: 10.3346/jkms.2005.20.4.659. PMID: 16100461. PMCID: PMC2782165.
Article
11. Demondion X, Vidal C, Glaude E, Subocz L, Francke JP, Cotten A. 2005; The posterior lumbar ramus: CT-anatomic correlation and propositions of new sites of infiltration. AJNR Am J Neuroradiol. 26:706–10. PMID: 15814909.
12. Danelich IM, Wright SS, Lose JM, Tefft BJ, Cicci JD, Reed BN. 2015; Safety of nonsteroidal antiinflammatory drugs in patients with cardiovascular disease. Pharmacotherapy. 35:520–35. DOI: 10.1002/phar.1584. PMID: 25940579.
Article
13. Handin RI. 2016; The history of antithrombotic therapy: the discovery of heparin, the vitamin K antagonists, and the utility of aspirin. Hematol Oncol Clin North Am. 30:987–93. DOI: 10.1016/j.hoc.2016.06.002. PMID: 27637302.
14. Smith DK, Demetriou T, Weber C. 2019; Aspirin for primary prevention: USPSTF recommendations for CVD and colorectal cancer. J Fam Pract. 68:146–51. PMID: 31039213.
15. MacKintosh ML, Crosbie EJ. 2018; Prevention strategies in endometrial carcinoma. Curr Oncol Rep. 20:101. DOI: 10.1007/s11912-018-0747-1. PMID: 30426278. PMCID: PMC6244901.
Article
16. Serrano D, Bonanni B, Brown K. 2019; Therapeutic cancer prevention: achievements and ongoing challenges - a focus on breast and colorectal cancer. Mol Oncol. 13:579–90. DOI: 10.1002/1878-0261.12461. PMID: 30690875. PMCID: PMC6396378.
Article
17. Hurwitz LM, Joshu CE, Barber JR, Prizment AE, Vitolins MZ, Jones MR, et al. 2019; Aspirin and non-aspirin NSAID use and prostate cancer incidence, mortality, and case fatality in the atherosclerosis risk in communities study. Cancer Epidemiol Biomarkers Prev. 28:563–9. DOI: 10.1158/1055-9965.EPI-18-0965. PMID: 30487131. PMCID: PMC6401240.
Article
18. Vane JR, Botting RM. 2003; The mechanism of action of aspirin. Thromb Res. 110:255–8. DOI: 10.1016/S0049-3848(03)00379-7. PMID: 14592543.
Article
19. Botting RM. 2010; Vane's discovery of the mechanism of action of aspirin changed our understanding of its clinical pharmacology. Pharmacol Rep. 62:518–25. DOI: 10.1016/S1734-1140(10)70308-X. PMID: 20631416.
Article
20. Tosco P, Lazzarato L. 2009; Mechanistic insights into cyclooxygenase irreversible inactivation by aspirin. ChemMedChem. 4:939–45. DOI: 10.1002/cmdc.200800438. PMID: 19301318.
Article
21. Lucido MJ, Orlando BJ, Vecchio AJ, Malkowski MG. 2016; Crystal structure of aspirin-acetylated human cyclooxygenase-2: insight into the formation of products with reversed stereochemistry. Biochemistry. 55:1226–38. DOI: 10.1021/acs.biochem.5b01378. PMID: 26859324. PMCID: PMC4775376.
Article
22. Chiang N, Serhan CN. 2004; Aspirin triggers formation of anti-inflammatory mediators: new mechanism for an old drug. Discov Med. 4:470–5. PMID: 20704950.
23. Brune K, Renner B, Tiegs G. 2015; Acetaminophen/paracetamol: a history of errors, failures and false decisions. Eur J Pain. 19:953–65. DOI: 10.1002/ejp.621. PMID: 25429980.
Article
24. Graham GG, Davies MJ, Day RO, Mohamudally A, Scott KF. 2013; The modern pharmacology of paracetamol: therapeutic actions, mechanism of action, metabolism, toxicity and recent pharmacological findings. Inflammopharmacology. 21:201–32. DOI: 10.1007/s10787-013-0172-x. PMID: 23719833.
Article
25. Candido KD, Perozo OJ, Knezevic NN. 2017; Pharmacology of acetaminophen, nonsteroidal antiinflammatory drugs, and steroid medications: implications for anesthesia or unique associated risks. Anesthesiol Clin. 35:e145–62. DOI: 10.1016/j.anclin.2017.01.020. PMID: 28526157.
Article
26. Schildknecht S, Daiber A, Ghisla S, Cohen RA, Bachschmid MM. 2008; Acetaminophen inhibits prostanoid synthesis by scavenging the PGHS-activator peroxynitrite. FASEB J. 22:215–24. DOI: 10.1096/fj.06-8015com. PMID: 17724253.
Article
27. Aminoshariae A, Khan A. 2015; Acetaminophen: old drug, new issues. J Endod. 41:588–93. DOI: 10.1016/j.joen.2015.01.024. PMID: 25732401.
Article
28. Smith HS. 2009; Potential analgesic mechanisms of acetaminophen. Pain Physician. 12:269–80.
29. Sasaki F, Yokomizo T. 2019; The leukotriene receptors as therapeutic targets of inflammatory diseases. Int Immunol. 31:607–15. DOI: 10.1093/intimm/dxz044. PMID: 31135881.
Article
30. Vyvey M. 2010; Steroids as pain relief adjuvants. Can Fam Physician. 56:1295–7.
31. Tager AM, Luster AD. 2003; BLT1 and BLT2: the leukotriene B(4) receptors. Prostaglandins Leukot Essent Fatty Acids. 69:123–34. DOI: 10.1016/S0952-3278(03)00073-5. PMID: 12895595.
Article
32. Pathan H, Williams J. 2012; Basic opioid pharmacology: an update. Br J Pain. 6:11–6. DOI: 10.1177/2049463712438493. PMID: 26516461. PMCID: PMC4590096.
Article
33. Kreek MJ, Borg L, Ducat E, Ray B. 2010; Pharmacotherapy in the treatment of addiction: methadone. J Addict Dis. 29:200–16. DOI: 10.1080/10550881003684798. PMID: 20407977. PMCID: PMC2885886.
Article
34. Ok HG, Kim SY, Lee SJ, Kim TK, Huh BK, Kim KH. 2018; Can oliceridine (TRV130), an ideal novel µ receptor G protein pathway selective (µ-GPS) modulator, provide analgesia without opioid-related adverse reactions? Korean J Pain. 31:73–9. DOI: 10.3344/kjp.2018.31.2.73. PMID: 29686804. PMCID: PMC5904350.
Article
35. Jensen TS, Finnerup NB. 2014; Allodynia and hyperalgesia in neuropathic pain: clinical manifestations and mechanisms. Lancet Neurol. 13:924–35. DOI: 10.1016/S1474-4422(14)70102-4. PMID: 25142459.
Article
36. Bennett MI, Attal N, Backonja MM, Baron R, Bouhassira D, Freynhagen R, et al. 2007; Using screening tools to identify neuropathic pain. Pain. 127:199–203. DOI: 10.1016/j.pain.2006.10.034. PMID: 17182186.
Article
37. Cruccu G, Truini A. 2009; Tools for assessing neuropathic pain. PLoS Med. 6:e1000045. DOI: 10.1371/journal.pmed.1000045. PMID: 19360134. PMCID: PMC2661248.
Article
38. Krause SJ, Backonja MM. 2003; Development of a neuropathic pain questionnaire. Clin J Pain. 19:306–14. DOI: 10.1097/00002508-200309000-00004. PMID: 12966256.
Article
39. Bouhassira D, Attal N, Alchaar H, Boureau F, Brochet B, Bruxelle J, et al. 2005; Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain. 114:29–36. DOI: 10.1016/j.pain.2004.12.010. PMID: 15733628.
Article
40. Bennett M. 2001; The LANSS Pain Scale: the Leeds assessment of neuropathic symptoms and signs. Pain. 92:147–57. DOI: 10.1016/S0304-3959(00)00482-6. PMID: 11323136.
Article
41. Portenoy R. 2006; Development and testing of a neuropathic pain screening questionnaire: ID Pain. Curr Med Res Opin. 22:1555–65. DOI: 10.1185/030079906X115702. PMID: 16870080.
Article
42. Freynhagen R, Baron R, Gockel U, Tölle TR. 2006; painDETECT: a new screening questionnaire to identify neuropathic components in patients with back pain. Curr Med Res Opin. 22:1911–20. DOI: 10.1185/030079906X132488. PMID: 17022849.
Article
43. Obermann M. 2010; Treatment options in trigeminal neuralgia. Ther Adv Neurol Disord. 3:107–15. DOI: 10.1177/1756285609359317. PMID: 21179603. PMCID: PMC3002644.
Article
44. Di Stefano G, Truini A, Cruccu G. 2018; Current and innovative pharmacological options to treat typical and atypical trigeminal neuralgia. Drugs. 78:1433–42. DOI: 10.1007/s40265-018-0964-9. PMID: 30178160. PMCID: PMC6182468.
Article
45. Montano N, Conforti G, Di Bonaventura R, Meglio M, Fernandez E, Papacci F. 2015; Advances in diagnosis and treatment of trigeminal neuralgia. Ther Clin Risk Manag. 11:289–99. DOI: 10.2147/TCRM.S37592. PMID: 25750533. PMCID: PMC4348120.
46. Headache Classification Subcommittee of the International Headache Society. 2004; The international classification of headache disorders: 2nd edition. Cephalalgia. 24(Suppl 1):9–160. DOI: 10.1111/j.1468-2982.2003.00824.x. PMID: 14979299.
47. Fricke-Galindo I, LLerena A, Jung-Cook H, López-López M. 2018; Carbamazepine adverse drug reactions. Expert Rev Clin Pharmacol. 11:705–18. DOI: 10.1080/17512433.2018.1486707. PMID: 29898616.
Article
48. Schmidt D, Elger CE. 2004; What is the evidence that oxcarbazepine and carbamazepine are distinctly different antiepileptic drugs? Epilepsy Behav. 5:627–35. DOI: 10.1016/j.yebeh.2004.07.004. PMID: 15380112.
Article
49. Zhou M, Chen N, He L, Yang M, Zhu C, Wu F. 2017; Oxcarbazepine for neuropathic pain. Cochrane Database Syst Rev. 12:CD007963. DOI: 10.1002/14651858.CD007963.pub3. PMID: 29199767. PMCID: PMC6486101.
Article
50. Senderovich H, Jeyapragasan G. 2018; Is there a role for combined use of gabapentin and pregabalin in pain control? Too good to be true? Curr Med Res Opin. 34:677–82. DOI: 10.1080/03007995.2017.1391756. PMID: 29023146.
Article
51. Kim ES, Deeks ED. 2016; Gabapentin enacarbil: a review in restless legs syndrome. Drugs. 76:879–87. DOI: 10.1007/s40265-016-0584-1. PMID: 27146056.
Article
52. Yang JY, Lee WI, Shin WK, Kim CH, Baik SW, Kim KH. 2013; Administration of four different doses of gabapentin reduces awakening from breakthrough pain and adverse effects in outpatients with neuropathic pain during the initial titration. Korean J Anesthesiol. 65:48–54. DOI: 10.4097/kjae.2013.65.1.48. PMID: 23904939. PMCID: PMC3726847.
Article
53. Serpell M, Latymer M, Almas M, Ortiz M, Parsons B, Prieto R. 2017; Neuropathic pain responds better to increased doses of pregabalin: an in-depth analysis of flexible-dose clinical trials. J Pain Res. 10:1769–76. DOI: 10.2147/JPR.S129832. PMID: 28794656. PMCID: PMC5536312.
Article
54. Domon Y, Arakawa N, Inoue T, Matsuda F, Takahashi M, Yamamura N, et al. 2018; Binding characteristics and analgesic effects of mirogabalin, a novel ligand for the α2δ subunit of voltage-gated calcium channels. J Pharmacol Exp Ther. 365:573–82. DOI: 10.1124/jpet.117.247551. PMID: 29563324.
Article
55. Javed S, Alam U, Malik RA. 2018; Mirogabalin and emerging therapies for diabetic neuropathy. J Pain Res. 11:1559–66. DOI: 10.2147/JPR.S145999. PMID: 30174455. PMCID: PMC6110292.
Article
56. Kim KH, Abdi S. 2014; Rediscovery of nefopam for the treatment of neuropathic pain. Korean J Pain. 27:103–11. DOI: 10.3344/kjp.2014.27.2.103. PMID: 24748937. PMCID: PMC3990817.
Article
57. Max MB, Gilron IH. Loeser JD, editor. 2000. Antidepressants, muscle relaxants, and N-methyl-D-aspartate receptor antagonists. Bonica's management of pain. 3rd ed. Lippincott Williams & Wilkins;Philadelphia (PA): p. 1710–26.
58. Choi YM, Kim KH. 2015; Etifoxine for pain patients with anxiety. Korean J Pain. 28:4–10. DOI: 10.3344/kjp.2015.28.1.4. PMID: 25589941. PMCID: PMC4293506.
Article
59. Shin SW, Lee JS, Abdi S, Lee SJ, Kim KH. 2019; Antipsychotics for patients with pain. Korean J Pain. 32:3–11. DOI: 10.3344/kjp.2019.32.1.3. PMID: 30671198. PMCID: PMC6333575.
Article
Full Text Links
  • KJP
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr