Changes in Descending Pain Modulation During Anti–Tumor Necrosis Factor Therapy: A Prospective Study in Rheumatoid Arthritis and Spondyloarthritis

Abstract

Objective

In rheumatoid arthritis (RA) and spondyloarthritis (SpA), managing persistent pain remains challenging. Little is known regarding impaired pain pathways in these patients and the impact of biologic disease-modifying antirheumatic drugs (bDMARDs). The objective of the Rheumatism Pain Inhibitory Descending Pathways study was to assess pain thresholds and descending pain modulation in patients with active RA or SpA following introduction of a tumor necrosis factor inhibitor (TNFi).

Methods

Patients with active disease (50 with RA and 50 with SpA) naive to bDMARDs or targeted synthetic DMARDs and starting a TNFi were included. Patients were observed for six months after TNFi initiation with clinical, psychological, and pain assessment. At all visits, participants underwent quantitative sensory testing with heat and cold pain thresholds and descending inhibition by conditioned pain modulation (CPM). Descending pain control (CPM effect) was assessed as the change in heat pain threshold (°C) following a conditioning stimulus.

Results

Of the 100 patients (59 women, mean ± SD age 45.8 ± 14.6 years), 74 completed the six-month follow-up. Thermal pain thresholds did not significantly change during follow-up. CPM effect improved significantly during follow-up (mean ± SD 0.25 ±2.57°C at baseline and 2.96 ± 2.50°C at six months; P < 0.001). At the end of follow-up, the mean CPM effect was significantly higher in patients without significant pain compared with patients with persistent pain (>3 of 10 on the Brief Pain Inventory) (mean ± SD 3.25 ± 2.68°C vs 2.47 ± 2.11°C; P = 0.04) and in patients achieving remission or low disease activity compared with patients with active rheumatism (mean ± SD 3.31 ± 2.68°C vs 2.18 ± 1.87°C; P = 0.01).

Conclusion

In active inflammatory rheumatisms, impaired descending pain modulation, but not thermal pain thresholds, is improved after TNFi treatment, suggesting a possible effect of TNFi on central pain modulation.