Peak B endorphin concentration in cerebrospinal fluid: reduced in chronic pain patients and increased during the placebo response

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Abstract
The level of an endogenous opioid (peak B endorphin) was measured in chromatographically fractionated cerebrospinal fluid (CSF) sampled from two groups of chronic pain patients before and after intrathecal saline (placebo) injection. As assessed by a verbal rating scale, one group reported no change in their level of pain (non-responders, NR;n=6) while the other group reported complete or >50% pain relief (placebo responders, PR;n=14). We find, as has been reported previously, that initial peak B levels were lower (by 50%) in these chronic pain patients' CSF than in CSF from pain-free (PF) normal controls (P0.4, pairedt-test). In contrast, a significant 2.3-fold increase was measured in the CSF peak B level of the PR group (Pt-test). This is the first direct evidence that a CSF opioid is correlated with placebo pain relief in chronic pain patients. Peak B is a potent analgesic substance when administered by the intracerebroventricular route in mice and its level is related to the patients' pain status in a presumably causal manner.