Anesth Pain Med.  2023 Oct;18(4):340-348. 10.17085/apm.23055.

Does adding muscle relaxant make post-operative pain better? a narrative review of the literature from US and European studies

• Verdiner R
• Khurmi N
• Choukalas C
• Erickson C
• Poterack K

• KMID: 2550913
• DOI: http://doi.org/10.17085/apm.23055

Abstract

Centrally acting skeletal muscle relaxants (CASMR) are widely prescribed as adjuncts for acute and chronic pain. Given the recent interest in multimodal analgesia and reducing opioid consumption, there has been an increase in its use for perioperative/postoperative pain control. The mechanism of action, pharmacodynamics, and pharmacokinetics of these drugs vary. Their use has been studied in a wide range of operative and non-operative settings. The best evidence for the efficacy of CASMRs is in acute, nonoperative musculoskeletal pain and, in the operative setting, in patients undergoing total knee arthroplasty and abdominal surgery, including inguinal herniorrhaphy and hemorrhoidectomy. The risk of complications and side effects, coupled with the limited evidence of efficacy, should prompt careful consideration of individual patient circumstances when prescribing CASMRs as part of perioperative pain management strategies.

Keyword

Analgesics; Muscle; Muscle relaxant; Pain; Pain management; Substance-related disorders

Reference

1. Soprano SE, Hennessy S, Bilker WB, Leonard CE. Assessment of physician prescribing of muscle relaxants in the United States, 2005-2016. JAMA Netw Open. 2020; 3:e207664.

2. Elenbaas JK. Centrally acting oral skeletal muscle relaxants. Am J Hosp Pharm. 1980; 37:1313–23.

3. Waldman HJ. Centrally acting skeletal muscle relaxants and associated drugs. J Pain Symptom Manage. 1994; 9:434–41.

4. Stanko JR. Review of oral skeletal muscle relaxants for the craniomandibular disorder (CMD) practitioner. Cranio. 1990; 8:234–43.

5. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, et al. DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008; 36(Database issue):D901–6.

6. Borenstein DG, Korn S. Efficacy of a low-dose regimen of cyclobenzaprine hydrochloride in acute skeletal muscle spasm: results of two placebo-controlled trials. Clin Ther. 2003; 25:1056–73.

7. Dapas F, Hartman SF, Martinez L, Northrup BE, Nussdorf RT, Silberman HM, et al. Baclofen for the treatment of acute low-back syndrome. A double-blind comparison with placebo. Spine (Phila Pa 1976). 1985; 10:345–9.

8. Pareek A, Chandurkar N, Chandanwale AS, Ambade R, Gupta A, Bartakke G. Aceclofenac-tizanidine in the treatment of acute low back pain: a double-blind, double-dummy, randomized, multicentric, comparative study against aceclofenac alone. Eur Spine J. 2009; 18:1836–42.

9. Toth PP, Urtis J. Commonly used muscle relaxant therapies for acute low back pain: a review of carisoprodol, cyclobenzaprine hydrochloride, and metaxalone. Clin Ther. 2004; 26:1355–67.

10. Shaheed CA, Maher CG, Williams KA, McLachlan AJ. Efficacy and tolerability of muscle relaxants for low back pain: Systematic review and meta-analysis. Eur J Pain. 2017; 21:228–37.

11. 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 (Phila Pa 1976). 2003; 28:1978–92.

12. Gouveia N, Rodrigues A, Ramiro S, Eusébio M, Machado PM, Canhão H, et al. The use of analgesic and other pain-relief drugs to manage chronic low back pain: results from a national survey. Pain Pract. 2017; 17:353–65.

13. Browning R, Jackson JL, O'Malley PG. Cyclobenzaprine and back pain: a meta-analysis. Arch Intern Med. 2001; 161:1613–20.

14. Friedman BW, Cisewski D, Irizarry E, Davitt M, Solorzano C, Nassery A, et al. A randomized, double-blind, placebo-controlled trial of naproxen with or without orphenadrine or methocarbamol for acute low back pain. Ann Emerg Med. 2018; 71:348–56.e5.

15. Friedman BW, Dym AA, Davitt M, Holden L, Solorzano C, Esses D, et al. Naproxen with cyclobenzaprine, oxycodone/acetaminophen, or placebo for treating acute low back pain: a randomized clinical trial. JAMA. 2015; 314:1572–80.

16. Aljuhani O, Kopp BJ, Patanwala AE. Patanwala, Effect of methocarbamol on acute pain after traumatic injury. Am J Ther. 2017; 24:e202–6.

17. Van Tulder MW, Koes BW, Bouter LM. Conservative treatment of acute and chronic nonspecific low back pain. A systematic review of randomized controlled trials of the most common interventions. Spine (Phila Pa 1976). 1997; 22:2128–56.

18. Deloney LP, Condeni MS, Carter C, Privette A, Leon S, Eriksson EA. Efficacy of methocarbamol for acute pain management in young adults with traumatic rib fractures. Ann Pharmacother. 2021; 55:705–10.

19. Abualnadi N, Dizon AM, Schiff L. Opioid adjuncts: optimizing opioid therapy with nonopioid medications. Clin Obstet Gynecol. 2019; 62:37–47.

20. Al Yafi MN, ElHawary H, Al-Halabi B, Alnaeem H, Xu L, Fouda-Neel O. Pain control following alloplastic breast reconstruction with muscle relaxant: A randomized controlled trial. J Plast Reconstr Aesthet Surg. 2021; 74:407–47.

21. Schneider MS. Pain reduction in breast augmentation using methocarbamol. Aesthetic Plast Surg. 1997; 21:23–4.

22. Hidalgo DA, Pusic AL. The role of methocarbamol and intercostal nerve blocks for pain management in breast augmentation. Aesthet Surg J. 2005; 25:571–5.

23. Selvin B. Myanesin: a study in postoperative pain relief. Anesthesiology. 1954; 15:174–8.

24. Nielsen RV, Fomsgaard JS, Siegel H, Martusevicius R, Mathiesen O, Dahl JB. The effect of chlorzoxazone on acute pain after spine surgery. A randomized, blinded trial. Acta Anaesthesiol Scand. 2016; 60:1152–60.

25. Chin KJ, Lewis S. Opioid-free analgesia for posterior spinal fusion surgery using erector spinae plane (ESP) blocks in a multimodal anesthetic regimen. Spine (Phila Pa 1976). 2019; 44:E379–83.

26. Blumenkopf B. Combination analgesic-antispasmodic therapy in postoperative pain. Spine (Phila Pa 1976). 1987; 12:384–7.

27. Johnson DS. The spasm-pain-spasm cycle. Pain Med. 2012; 13:615.

28. Gong L, Dong JY, Li ZR. Effects of combined application of muscle relaxants and celecoxib administration after total knee arthroplasty (TKA) on early recovery: a randomized, double-blind, controlled study. J Arthroplasty. 2013; 28:1301–5.

29. Ban VS, Bhoja R, McDonagh DL. Multimodal analgesia for craniotomy. Curr Opin Anaesthesiol. 2019; 32:592–9.

30. Fry EN. Postoperative analgesia using papaveretum and orphenadrine. A preliminary trial. Anaesthesia. 1979; 34:281–3.

31. Bharti N, Dontukurthy S, Bala I, Singh G. Postoperative analgesic effect of intravenous (i.v.) clonidine compared with clonidine administration in wound infiltration for open cholecystectomy. Br J Anaesth. 2013; 111:656–61.

32. Techanivate A, Dusitkasem S, Anuwattanavit C. Dexmedetomidine compare with fentanyl for postoperative analgesia in outpatient gynecologic laparoscopy: a randomized controlled trial. J Med Assoc Thai. 2012; 95:383–90.

33. Guen ML, Liu N, Tounou F, Augé M, Tuil O, Chazot T, et al. Dexmedetomidine reduces propofol and remifentanil requirements during bispectral index-guided closed-loop anesthesia: a double-blind, placebo-controlled trial. Anesth Analg. 2014; 118:946–55.

34. Malanga GA, Gwynn MW, Smith R, Miller D. Tizanidine is effective in the treatment of myofascial pain syndrome. Pain Physician. 2002; 5:422–32.

35. A double-blind, placebo-controlled trial of tizanidine in the treatment of spasticity caused by multiple sclerosis. United Kingdom Tizanidine Trial Group. Neurology. 1994; 44(11 Suppl 9):S70–8.

36. Semenchuk MR, Sherman S. Effectiveness of tizanidine in neuropathic pain: an open-label study. J Pain. 2000; 1:285–92.

37. Yazicioğlu D, Caparlar C, Akkaya T, Mercan U, Kulaçoğlu H. Tizanidine for the management of acute postoperative pain after inguinal hernia repair: a placebo-controlled double-blind trial. Eur J Anaesthesiol. 2016; 33:215–22.

38. Keppel Hesselink JM, Kopsky DJ, Sajben NL. Vulvodynia and proctodynia treated with topical baclofen 5 % and palmitoylethanolamide. Arch Gynecol Obstet. 2014; 290:389–93.

39. Kopsky DJ, Keppel Hesselink JM. Neuropathic pain as a result of acromegaly, treated with topical baclofen cream. J Pain Symptom Manage. 2013; 46:e4–5.

40. Barton DL, Wos EJ, Qin R, Mattar BI, Green NB, Lanier KS, et al. A double-blind, placebo-controlled trial of a topical treatment for chemotherapy-induced peripheral neuropathy: NCCTG trial N06CA. Support Care Cancer. 2011; 19:833–41.

41. Ala S, Alvandipour M, Saeedi M, Mansourifar M, Monajati M, Shiva A. Effect of topical baclofen 5% on post-hemorrhoidectomy pain: randomized double blind placebo-controlled clinical trial. J Gastrointest Surg. 2020; 24:405–10.

42. Ahiskalioglu A, AYayik AM, Ahiskalioglu EO, Dostbil A, Doymus O, Erdem Karadeniz E, et al. Ultrasound-guided bilateral superficial cervical block and preemptive single-dose oral tizanidine for post-thyroidectomy pain: a randomized-controlled double-blind study. J Anesth. 2018; 32:219–26.

43. Lataste X, Emre M, Davis C, Groves L. Comparative profile of tizanidine in the management of spasticity. Neurology. 1994; 44(11 Suppl 9):S53–9.

44. Kirmeier R, Truschnegg A, Payer M, Acham S, Schulz K, Jakse N. Evaluation of a muscle relaxant on sequelae of third molar surgery: a pilot study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007; 104:e8–14.

45. De Santana Santos T, Calazans ACM, Martins-Filho PRS, da Silva LCF, E Silva EDDO, Gomes ACA. Evaluation of the muscle relaxant cyclobenzaprine after third-molar extraction. J Am Dent Assoc. 2011; 142:1154–62.

46. Inge TH, Owings E, Blewett CJ, Baldwin CE, Cain WS, Hardin W, et al. Reduced hospitalization cost for patients with pectus excavatum treated using minimally invasive surgery. Surg Endosc. 2003; 17:1609–13.

47. Elder NC. Abuse of skeletal muscle relaxants. Am Fam Physician. 1991; 44:1223–6.

48. Preston KL, Guarino JJ, Kirk WT, Griffiths RR. Evaluation of the abuse potential of methocarbamol. J Pharmacol Exp Ther. 1989; 248:1146–57.

49. Di Gangi S, Pichierri G, Zechmann S, Rosemann T, Plate A. Prescribing patterns of pain medications in unspecific low back pain in primary care: A retrospective analysis. J Clin Med. 2021; 10:1366.

50. Paulozzi LJ, Strickler GK, Kreiner PW, Koris CM; Centers for Disease Control and Prevention (CDC). Controlled substance prescribing patterns—prescription behavior surveillance system, eight states, 2013. MMWR Surveill Summ. 2015; 64:1–14.

51. Golden AG, Ma Q, Nair V, Florez HJ, Roos BA. Risk for fractures with centrally acting muscle relaxants: an analysis of a national Medicare Advantage claims database. Ann Pharmacother. 2010; 44:1369–75.

52. Spence MM, Shin PJ, Lee EA, Gibbs NE. Risk of injury associated with skeletal muscle relaxant use in older adults. Ann Pharmacother. 2013; 47:993–8.

53. Gonzalez LA, Gatch MB, Taylor CM, Bell-Horner CL, Forster MJ, Dillon GH. Carisoprodol-mediated modulation of GABAA receptors: in vitro and in vivo studies. J Pharmacol Exp Ther. 2009; 329:827–37.

54. Starr S, Sherba RT, Gersper B. Ohio substance abuse monitoring network: surveillance of drug abuse trends in the state of Ohio: June 2014–January 2015. Columbus, OH: Ohio Department of Mental Health and Addiction Services;2015. p. 167.

55. Horsfall JT, Sprague JE. The pharmacology and toxicology of the 'holy trinity'. Basic Clin Pharmacol Toxicol. 2017; 120:115–9.

56. Li Y, Delcher C, Wei YJJ, Reisfield GM, Brown JD, Tighe P, et al. Risk of opioid overdose associated with concomitant use of opioids and skeletal muscle relaxants: a population-based cohort study. Clin Pharmacol Ther. 108; 120:81–9.

57. Barroso AB, Lima V, Guzzo GC, Moraes RA, Vasconcellos MC, Bezerra MM, et al. Efficacy and safety of combined piroxicam, dexamethasone, orphenadrine, and cyanocobalamin treatment in mandibular molar surgery. Braz J Med Biol Res. 2006; 39:1241–7.

58. Gordon NC, Gear RW, Heller PH, Paul S, Miaskowski C, Levine JD. Enhancement of morphine analgesia by the GABAB agonist baclofen. Neuroscience. 1995; 69:345–9.

59. Harris AB, Puvanesarajah V, Marrache M, Gottlich CP, Raad M, Skolasky RL, et al. Opioid prescribing practices after posterior spinal arthrodesis for adolescent idiopathic scoliosis. Spine Deform. 2020; 8:965–73.