Muscle relaxants and neuromodulators for managing RA pain: Many options, but no clear successes

Pain management is a high priority for patients with rheumatoid arthritis, so three researchers in Australia analysed existing study data to see whether two different classes of drugs can help. When looking at muscle relaxants, they discovered that neither the benzodiazepine agents, diazepam and triazolam, nor the non- benzodiazepine agent, zopiclone, reduce pain when taken for one to 14 days. However, even this short use was associated for both agents with drowsiness and dizziness.

When looking at neuromodulators, the researchers discovered weak evidence that using oral nefopam, topical capsaicin and oromucosal cannabis for one to seven days can reduce pain in patients with rheumatoid arthritis better than placebo. Each drug has its own set of side effects, but together they included nausea, sweating, dizziness, dry mouth light headedness, local burning and irritation. Accessibility to these medications is also an issue with nefopam not being widely available in many countries and cannabis use illegal in many parts of the world. These results are published in The Cochrane Library in two separate papers.

"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. In view of the low quality of the evidence we found to support this option, some caution should be applied," says lead researcher Bethan Richards, who works at the Institute of Rheumatology and Orthopedics, Royal Prince Alfred Hospital, Camperdown, Australia. "However, oral nefopam and oromucosal cannabis have more significant side effect profiles and the potential harms seem to outweigh any modest benefit achieved."

Rheumatoid arthritis is a disease in which a people's immune systems, which normally fight infection, attack the lining of their joints. This makes the joints swollen, stiff, and painful. The small joints of their hands and feet are usually affected first. There is currently no cure for rheumatoid arthritis, so the treatments aim to relieve pain and stiffness and improve their mobility.

Muscle relaxants can be used to treat anxiety and promote sleep, and some people believe they may also reduce pain by acting on the nerves that cause pain, but this remains controversial. Neuromodulators alter the way nerves communicate with each other and, consequently, alter the overall activity level of the brain. This may reduce the amount of pain felt by an individual.

The researchers looked for clinical studies that had compared these drugs with either other active treatments or placebos. After searching through the major clinical databases they found only a few, small trials. For muscle relaxants, they found six trials that had a total of 126 participants, and for the neuromodulators they found four trials that involved 141 participants. The data was further weakened because the procedures used in the trials ran the risk that the patients or those running the trials could have affected the findings.

"Given the large number of people with rheumatoid arthritis, and the debilitating affect that the disease has on their lives, it is disappointing that no high-quality studies have been carried out on these drugs in this patient group," says Richards.

The researchers suggest that "to better assess the efficacy and safety of medications for pain management in patients with rheumatoid arthritis, large high quality, double-blind placebo-controlled trials are now required."