The association between psychopathology and placebo analgesia in patients with discogenic low back pain

Chronic low back pain patients have a high rate of psychopathology, comprised mainly of depression, anxiety, and high levels of neuroticism. We previously found that psychopathology is associated with increased placebo analgesia in this patient group.

To better understand this finding in the context of other known predictors of placebo response (such as expectations for relief), we performed a detailed analysis of expectations and other possible covariates.

We conducted a double-blind, placebo-controlled, randomized, crossover-designed trial of intravenous morphine vs. placebo in 60 subjects with chronic low back pain and discogenic abnormalities. Patients were stratified into three groups of psychiatric symptom severity (Low, Moderate, and High), based on composite scores on depression, anxiety for pain, and neuroticism scales. Subjects were given intravenous morphine and placebo in random order on separate visits, and completed serial pain ratings over 3 h at each session.

With 20 subjects per group, there were small, but significant differences between groups in baseline pain ratings. No differences were found between groups in age, gender, and radicular pain. Patients with low psychological symptomatology reported 7.7% total pain relief with placebo compared with 23.4% in the Moderate group and 23.5% in the High group (P < 0.05). Expectations were not significantly different between groups, but in the High group expectation levels predicted placebo analgesia (P < 0.001). Neuropathic pain quality was also a predictor (P < 0.05).

This study indicates that high and moderate levels of psychopathology are associated with heightened placebo analgesia in chronic low back pain patients. Expectations were only an influence in the high psychopathology group, and neuropathic pain affects placebo responses. These findings have implications for future research characterizing placebo responders.