Meta-analysis of placebo responses in central neuropathic pain: Impact of subject, study, and pain characteristics

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Study identified factors that contribute to variable placebo responses in clinical trials involving individuals with central neuropathic pain. Defined as a reduction in pain in the placebo arm of a clinical trial, the “placebo response” includes the placebo effect (the true psychobiological effects causing a reduction in pain) in addition to other contributing factors, such as natural history, and patient biases. A systematic review and meta-analysis was performed of placebo-controlled trials examining pharmacological and noninvasive brain stimulation interventions for central neuropathic pain. Study design, subject characteristics, and pain ratings for the placebo group were extracted from each trial. Pooling of results and identification of moderating factors were carried out using random effects meta-analysis and meta-regression techniques. A total of 39 published trials met the inclusion criteria: 26 involving individuals with spinal cord injury (SCI), 6 with stroke, and 7 with multiple sclerosis (MS). No significant publication bias was detected. Overall, there was a significant effect for placebo to reduce central pain. Smaller placebo responses were associated with crossover-design studies, longer pain duration, and greater between-subject baseline pain variability. There were no significant effects for neurological condition (stroke, MS, or SCI) or the type of intervention (pharmacological versus noninvasive brain stimulation). In a planned subanalysis, the severity of damage in the spinal cord also had no significant effect on the placebo response. Further study is warranted to identify factors that may explain the impact of pain duration on the placebo response at the individual subject level.

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