Pain Persists Long after RA Inflammation Subsides

In early rheumatoid arthritis, disease activity and pain do not necessarily occur in parallel. A new study shows that pain still persists post treatment and suggests that pain should be evaluated separately. “We found that in spite of a good inflammatory response to methotrexate after three months, almost a third of these patients reported remaining pain to an extent that has previously been defined as over an acceptable level to the individual,” the authors of the study wrote.  Controlling inflammation in rheumatoid arthritis has been the hallmark of new therapies and rightfully so. These therapies have improved long-term outcomes for patients, but existing disease-modifying anti-rheumatic drugs (DMARDs) are not necessarily designed to treat ongoing pain. Published in the Jan. 19 issue of Arthritis Care and Research, the study is based on the results of 1,241 early rheumatoid arthritis patients who received methotrexate (MTX) as the only DMARD at diagnosis. The data was obtained from the Swedish Rheumatology Quality Register. Researchers found that 60 percent of early rheumatoid arthritis patients receiving methotrexate therapy for three months still have pain, even though 40 percent had a good clinical response to methotrexate, 38 percent had a moderate response and 23 percent reported no improvement. In terms of pain post treatment:  30 percent of patients who had a good clinical response to methotrexate therapy had pain greater than 20 mm VAS as compared to 70 percent of patients with moderate response and 83 percent of patients with no improvement. These patients showed more disability and greater discomfort. Patient global assessment (PGA) levels were higher as were 28-tender joint count (28-TJC), CRP and DAS28 scores. “These data show that significant pain after good clinical response is common in early RA, and support the need for more intensive pain control early in the disease,” wrote the authors of the study, which was led by Jon Lampa, M.D., Ph.D., of the Karolinska Institute in Sweden. Patients with pain post methotrexate treatment were defined as those having a Visual Analogue Scale (VAS) score of greater than 20 mm (on a scale of 0-100 mm), which was considered significant pain.  The patients were assessed at diagnosis and three-month post methotrexate treatment. More disability at baseline was associated with the presence of pain post treatment as was a higher PGA levels, however, the study reports that pain post treatment was not associated with 28-swollen joint count (28-SJC), 28-TJC, C-reactive protein (CRP), current smoking, RF and anti-CCP positivity. They found that a combination of 20 mm VAS or higher, with low inflammatory activity at three months follow-up, was associated with 37 percent of patients.  In this group remaining pain significantly associated with baseline HAQ (OR 1.45 (95%CI=1.17-1.79) and baseline ESR (OR 0.86 (95%CI=0.81-0.91). In addition, remaining pain was significantly associated with the following baseline parameters:  CRP (adj. OR 0.83 (95%CI=0.79-0.88), PGA (adj. OR 1.1 (95%CI=1.05-1.16) and 28-TJC(adj. OR 1.04 (95%CI=1.01 – 1.06). The authors say their findings highlight an important issue:  limitations of current treatment strategies. Generalized and widespread pain in rheumatoid arthritis could be related to nerve damage caused by inflammation, other studies have shown. This could lead to long-term sensitization and as a result, chronic pain.[[{"type":"media","view_mode":"media_crop","fid":"45125","attributes":{"alt":"@chingyunsongShutterstock.com","class":"media-image media-image-right","id":"media_crop_7011585999280","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"5117","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"font-size: 13.008px; line-height: 1.538em; float: right;","title":"@chingyunsongShutterstock.com","typeof":"foaf:Image"}}]] In rheumatoid arthritis, abnormally heightened sensitivity to pain was known to exist in rheumatoid arthritis, but it’s never before been shown in early rheumatoid arthritis. “It can be assumed that a significant portion of these patients, during disease course, may have developed peripheral pain sensitization, which is refractory to both anti-rheumatic and anti-inflammatory therapy,” the authors wrote. Current treatments are designed to suppress joint inflammation, not necessarily relieve pain. “If dysregulated pain thresholds, hyperalgesia and allodynia have been established, these conditions are usually not reversible by immune suppression,” the authors wrote. The authors explained pain without inflammation as early joint destruction, enthesitis, the development of widespread pain and the development of fibromyalgia. Rheumatologists should closely follow pain assessments in all of their rheumatoid arthritis patients, not just high-risk pain patients with fibromyalgia-like disease at diagnosis, the authors wrote. “Attempts to improve coping strategies for pain may be of value as additional therapeutic strategies to anti-rheumatic and pain treatment in early RA,” the authors wrote. 

References:

Reem Altawil, Saedis Saevarsdottir, et. al.

"Remaining pain is common in early rheumatoid arthritis patients treated with methotrexate,"

Arthritis Care and Research

. Accepted manuscript online: 19 JAN 2016 11:54AM EST | DOI: 10.1002/acr.22790