The neurologic pain signature responds to nonsteroidal anti-inflammatory treatment vs placebo in knee osteoarthritis

Supplemental Digital Content is Available in the Text. fMRI-based measures, validated for nociceptive pain, respond to acute osteoarthritis pain, are not sensitive to placebo, and are mild-to-moderately sensitive to naproxen. Abstract Introduction: Many drug trials for chronic pain fail because of high placebo response rates in primary endpoints. Neurophysiological measures can help identify pain-linked pathophysiology and treatment mechanisms. They can also help guide early stop/go decisions, particularly if they respond to verum treatment but not placebo. The neurologic pain signature (NPS), an fMRI-based measure that tracks evoked pain in 40 published samples and is insensitive to placebo in healthy adults, provides a potentially useful neurophysiological measure linked to nociceptive pain. Objectives: This study aims to validate the NPS in knee osteoarthritis (OA) patients and test the effects of naproxen on this signature. Methods: In 2 studies (50 patients, 64.6 years, 75% females), we (1) test the NPS and other control signatures related to negative emotion in knee OA pain patients; (2) test the effect of placebo treatments; and (3) test the effect of naproxen, a routinely prescribed nonsteroidal anti-inflammatory drug in OA. Results: The NPS was activated during knee pain in OA (d = 1.51, P < 0.001) and did not respond to placebo (d = 0.12, P = 0.23). A single dose of naproxen reduced NPS responses (vs placebo, NPS d = 0.34, P = 0.03 and pronociceptive NPS component d = 0.38, P = 0.02). Naproxen effects were specific for the NPS and did not appear in other control signatures. Conclusion: This study provides preliminary evidence that fMRI-based measures, validated for nociceptive pain, respond to acute OA pain, do not appear sensitive to placebo, and are mild-to-moderately sensitive to naproxen.