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

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 5 1.51, P , 0.001) and did not respond to placebo (d 5 0.12, P 5 0.23). A single dose of naproxen reduced NPS responses (vs placebo, NPS d 5 0.34, P 5 0.03 and pronociceptive NPS component d 5 0.38, P 5 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.

Brain mediators of negative affect-induced physical symptom reporting in patients with functional somatic syndromes

“…In that account, symptoms are thought to arise as the end product of a hierarchical inferential process in the brain, involving two counter-flowing streams of information, namely afferent input on the one hand and predictions from the brain on the other hand. The relative contributions of the somatic input and the predictions are determined by their respective precisions (or statistical confidence) [ 6 , 43 ]. A symptom perception account of FSS assumes reduced detail in somatosensory processing, leaving more room for prediction-based contextual information to determine the eventual somatic percept.…”

“…Second, we used mediation as a statistical method, which does not allow us to make strong claims about causality, particularly given the cross-sectional rather than longitudinal nature of the data. Third, the fact that the majority (76%) of the included patients were on medication could be considered a limitation, especially in the light of recent findings that the NPS is responsive to analgesic drug effects on acute evoked pain perception in osteoarthritis patients (which is to be expected for a nociceptive pain signature) [ 43 ]. However, analgesics dampened both subjective and NPS responses in this study, hence medication effects are unlikely to explain the relatively increased NPS response in patients versus controls in the present study.…”

Biological Targets of Multimolecular Therapies in Middle-Age Osteoarthritis

“…For example, naproxen has shown relatively good efficacy when used by patients with a predominant neuropathic pain component. 43 On the other hand, psychotropic drugs, such as duloxetine, which is a serotonin-noradrenalin re-uptake inhibitor, is recommended for chronic pain from hyperalgesia and central sensitization. 44 At present, the effects of duloxetine on hyperalgesia and central sensitization in knee OA are under investigation.…”

“…Identification of pain signatures, based on neurophysiology, has prompted new pharmacological investigations to target OA pain phenotypes accurately. For example, naproxen has shown relatively good efficacy when used by patients with a predominant neuropathic pain component 43. On the other hand, psychotropic drugs, such as duloxetine, which is a serotonin-noradrenalin re-uptake inhibitor, is recommended for chronic pain from hyperalgesia and central sensitization 44.…”