Chronic Pain in Inflammatory Arthritis: Mechanisms, Metrology, and Emerging Targets—A Focus on the JAK-STAT Pathway

Table 2

Principal Cochrane systematic reviews on pain management in inflammatory arthritis.

Topics	Main conclusions
Opioids (Whittle et al. [133])	(i) Limited evidence that weak oral opioids may be effective analgesics for some patients with rheumatoid arthritis, but adverse effects are common and may offset the benefits of this class of medications.
	(ii) Insufficient evidence to conclude regarding the use of weak opioids for longer than six weeks or the role of strong opioids.
Neuromodulators (Richards et al. [135])	(i) Weak evidence that oral nefopam, topical capsaicin, and oromucosal cannabis are all superior to placebo in reducing pain in rheumatoid arthritis patients.
	(ii) Capsaicin could be considered as an add-on therapy for patients with persistent local pain and inadequate response or intolerance to other treatments.
Antidepressants (Richards et al. [139])	(i) Insufficient evidence to support the routine prescription of antidepressants as pain modulators in rheumatoid arthritis patients since no reliable conclusions about their efficacy can be gathered from eight placebo randomized controlled trials.
Pain management in rheumatoid arthritis and cardiovascular or renal comorbidity (Marks et al. [141])	(i) Absence of specific evidence in rheumatoid arthritis.
	(ii) Guidelines recommend that nonsteroidal anti-inflammatory drugs should be used with caution in the general rheumatoid arthritis population, with the need of extra vigilance in patients with established cardiovascular disease or risk factors.
	(iii) Guidelines regarding the use of nonsteroidal anti-inflammatory drugs and opioids in moderate-to-severe renal impairment should also be applied to the rheumatoid arthritis population.
Pain management in inflammatory arthritis and gastrointestinal or liver comorbidity (Radner et al. [142])	(i) Scarce evidence to guide clinicians about how gastrointestinal or liver comorbidities should influence the choice of pain therapy.
	(ii) Nonsteroidal anti-inflammatory drugs should be used cautiously in patients with inflammatory arthritis and a history of gastrointestinal comorbidity since the evidence that they may be at increased risk is consistent.
Combination therapy for pain management in inflammatory arthritis (Ramiro et al. [140])	(i) Insufficient evidence to agree upon the value of combination therapy over monotherapy.
	(ii) No studies have addressed the value of combination therapy for patients with inflammatory arthritis having persistent pain despite optimal inflammation control.