Display options
Cite
Richards BL, Whittle SL, Buchbinder R. Neuromodulators for pain management in rheumatoid arthritis. Cochrane Database Syst Rev. 2012;1:CD008921doi: 10.1002/14651858.CD008921.pub2.
Richards, B. L., Whittle, S. L., & Buchbinder, R. (2012). Neuromodulators for pain management in rheumatoid arthritis. The Cochrane database of systematic reviews, 1CD008921. https://doi.org/10.1002/14651858.CD008921.pub2
Richards, Bethan L, et al. "Neuromodulators for pain management in rheumatoid arthritis." The Cochrane database of systematic reviews vol. 1 (2012): CD008921. doi: https://doi.org/10.1002/14651858.CD008921.pub2
Richards BL, Whittle SL, Buchbinder R. Neuromodulators for pain management in rheumatoid arthritis. Cochrane Database Syst Rev. 2012 Jan 18;1:CD008921. doi: 10.1002/14651858.CD008921.pub2. PMID: 22258992; PMCID: PMC6956614.
Copy Download .nbib Format: NLM
Share it on

Cochrane Database Syst Rev. 2012 Jan 18;1:CD008921. doi: 10.1002/14651858.CD008921.pub2.

Neuromodulators for pain management in rheumatoid arthritis.

The Cochrane database of systematic reviews

Bethan L Richards, Samuel L Whittle, Rachelle Buchbinder

Affiliations

  1. Institute of Rheumatology and Orthopedics, Royal Prince Alfred Hospital, Camperdown, Australia. [email protected].

PMID: 22258992 PMCID: PMC6956614 DOI: 10.1002/14651858.CD008921.pub2

Abstract

BACKGROUND: Pain management is a high priority for patients with rheumatoid arthritis (RA). Despite deficiencies in research data, neuromodulators have gained widespread clinical acceptance as adjuvants in the management of patients with chronic musculoskeletal pain.

OBJECTIVES: The aim of this review was to determine the efficacy and safety of neuromodulators in pain management in patients with RA. Neuromodulators included in this review were anticonvulsants (gabapentin, pregabalin, phenytoin, sodium valproate, lamotrigine, carbamazepine, levetiracetam, oxcarbazepine, tiagabine and topiramate), ketamine, bupropion, methylphenidate, nefopam, capsaicin and the cannabinoids.

SEARCH METHODS: We performed a computer-assisted search of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, 4th quarter), MEDLINE (1950 to week 1 November 2010), EMBASE (Week 44, 2010) and PsycINFO (1806 to week 2 November 2010). We also searched the 2008 and 2009 American College of Rheumatology (ACR) and European League against Rheumatism (EULAR) conference abstracts and performed a handsearch of reference lists of articles.

SELECTION CRITERIA: We included randomised controlled trials which compared any neuromodulator to another therapy (active or placebo, including non-pharmacological therapies) in adult patients with RA that had at least one clinically relevant outcome measure.

DATA COLLECTION AND ANALYSIS: Two blinded review authors independently extracted data and assessed the risk of bias in the trials. Meta-analyses were used to examine the efficacy of a neuromodulator on pain, depression and function as well as their safety.

MAIN RESULTS: Four trials with high risk of bias were included in this review. Two trials evaluated oral nefopam (52 participants) and one trial each evaluated topical capsaicin (31 participants) and oromucosal cannabis (58 participants).The pooled analyses identified a significant reduction in pain levels favouring nefopam over placebo (weighted mean difference (WMD) -21.16, 95% CI -35.61 to -6.71; number needed to treat (NNT) 2, 95% CI 1.4 to 9.5) after two weeks. There were insufficient data to assess withdrawals due to adverse events. Nefopam was associated with significantly more adverse events (RR 4.11, 95% CI 1.58 to 10.69; NNTH 9, 95% CI 2 to 367), which were predominantly nausea and sweating.In a mixed population trial, qualitative analysis of patients with RA showed a significantly greater reduction in pain favouring topical capsaicin over placebo at one and two weeks (MD -23.80, 95% CI -44.81 to -2.79; NNT 3, 95% CI 2 to 47; MD -34.40, 95% CI -54.66 to -14.14; NNT 2, 95% CI 1.4 to 6 respectively). No separate safety data were available for patients with RA, however 44% of patients developed burning at the site of application and 2% withdrew because of this.One small, low quality trial assessed oromucosal cannabis against placebo and found a small, significant difference favouring cannabis in the verbal rating score 'pain at present' (MD -0.72, 95% CI -1.31 to -0.13) after five weeks. Patients receiving cannabis were significantly more likely to suffer an adverse event (risk ratio (RR) 1.82, 95% CI 1.10 to 3.00; NNTH 3, 95% CI 3 to 13). These were most commonly dizziness (26%), dry mouth (13%) and light headedness (10%).

AUTHORS' CONCLUSIONS: There is currently weak evidence that oral nefopam, topical capsaicin and oromucosal cannabis are all superior to placebo in reducing pain in patients with RA. However, each agent is associated with a significant side effect profile. The confidence in our estimates is not strong given the difficulties with blinding, the small numbers of participants evaluated and the lack of adverse event data. In some patients, however, even a small degree of pain relief may be considered worthwhile. Until further research is available, given the relatively mild nature of the adverse events, capsaicin could be considered as an add-on therapy for patients with persistent local pain and inadequate response or intolerance to other treatments. Oral nefopam and oromucosal cannabis have more significant side effect profiles however and the potential harms seem to outweigh any modest benefit achieved.

References

  1. Epilepsia. 1988 Sep-Oct;29(5):582-3 - PubMed
  2. Pain. 1997 Jun;71(2):179-86 - PubMed
  3. Pain Res Manag. 2005 Autumn;10 Suppl A:7A-14A - PubMed
  4. Support Cancer Ther. 2007 Sep 1;4(4):241-6 - PubMed
  5. J Pain. 2008 Feb;9(2):105-21 - PubMed
  6. Toxicon. 2009 Oct;54(5):658-67 - PubMed
  7. Prog Neurobiol. 2001 Apr;63(5):569-611 - PubMed
  8. Cochrane Database Syst Rev. 2011 Jan 19;(1):CD008257 - PubMed
  9. J Pain Symptom Manage. 2000 Nov;20(5):358-73 - PubMed
  10. Pain. 2005 Dec 5;118(3):289-305 - PubMed
  11. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD004603 - PubMed
  12. Eur J Pharmacol. 1987 Jun 12;138(1):77-82 - PubMed
  13. Arthritis Rheum. 1980 Feb;23(2):137-45 - PubMed
  14. Lancet. 1999 Jun 5;353(9168):1959-64 - PubMed
  15. Clin Rheumatol. 1988 Sep;7(3):411-2 - PubMed
  16. Pain. 2007 Dec 5;132(3):237-251 - PubMed
  17. J Rheumatol. 1995 Jul;22(7):1235-40 - PubMed
  18. Support Care Cancer. 2007 Apr;15(4):363-72 - PubMed
  19. Pain. 2010 Sep;150(3):386-389 - PubMed
  20. Neurology. 2009 Apr 28;72(17):1473-8 - PubMed
  21. Cochrane Database Syst Rev. 2003;(1):CD003351 - PubMed
  22. Pain Res Manag. 2001 Summer;6(2):74-9 - PubMed
  23. Joint Bone Spine. 2009 Mar;76(2):190-4 - PubMed
  24. Neuropharmacology. 1993 Oct;32(10):995-9 - PubMed
  25. Cochrane Database Syst Rev. 2011 Feb 16;(2):CD002948 - PubMed
  26. BMJ. 2004 Apr 24;328(7446):991 - PubMed
  27. Drugs. 2000 Nov;60(5):1029-52 - PubMed
  28. Arthritis Rheum. 1983 Nov;26(11):1346-53 - PubMed
  29. Cochrane Database Syst Rev. 2007 Apr 18;(2):CD006044 - PubMed
  30. Rheumatology (Oxford). 2003 Oct;42(10):1133-7 - PubMed
  31. Cochrane Database Syst Rev. 2005 Jul 20;(3):CD005452 - PubMed
  32. J Clin Rheumatol. 2009 Feb;15(1):35-8 - PubMed
  33. Drugs. 1980 Apr;19(4):249-67 - PubMed
  34. BMJ. 2001 Jul 7;323(7303):13-6 - PubMed
  35. PM R. 2010 Apr;2(4):268-76 - PubMed
  36. Clin Ther. 1991 May-Jun;13(3):383-95 - PubMed
  37. Eur J Pharmacol. 1981 Sep 11;74(2-3):135-40 - PubMed
  38. Br J Rheumatol. 1986 Feb;25(1):72-6 - PubMed
  39. Nature. 1998 Jul 16;394(6690):277-81 - PubMed
  40. Pain. 1999 May;81(1-2):135-45 - PubMed
  41. Handb Exp Pharmacol. 2005;(168):509-54 - PubMed
  42. Arthritis Res Ther. 2009;11(3):R61 - PubMed
  43. Ann Rheum Dis. 1987 Sep;46(9):667-9 - PubMed
  44. Pain. 1998 Jun;76(3):395-406 - PubMed
  45. Cochrane Database Syst Rev. 2009 Jul 08;(3):CD007442 - PubMed
  46. J Rheumatol. 1992 Apr;19(4):604-7 - PubMed
  47. Ann Neurol. 2008 Sep;64(3):274-83 - PubMed
  48. Br J Anaesth. 2008 Nov;101(5):610-7 - PubMed
  49. Transl Res. 2009 May;153(5):205-16 - PubMed
  50. J Clin Dent. 1994;5(2):54-9 - PubMed
  51. Pain Med. 2009 Nov;10(8):1353-68 - PubMed
  52. J Rheumatol. 2011 Mar;38(3):409-18 - PubMed
  53. Rheumatology (Oxford). 2006 Jan;45(1):50-2 - PubMed
  54. Eur J Pharmacol. 1986 Sep 9;128(3):157-64 - PubMed
  55. JAMA. 2004 Sep 15;292(11):1363-4 - PubMed
  56. Arthritis Rheum. 2002 Aug;47(4):391-7 - PubMed

Substances

MeSH terms

Publication Types