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 greater than 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 (P less than 0.001, t-test). Peak B levels measured from CSF of the NR group undergoing this procedure did not change (P greater than 0.4, paired t-test). In contrast, a significant 2.3-fold increase was measured in the CSF peak B level of the PR group (P less than 0.05, paired t-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.
The pain tolerance latencies of 10 chronic pain patients were evaluated by heat beam dolorimetry (stimulus intensity 15.33 mW.cm-2.sec-1) prior to and following administration of morphine by intrathecal (n = 5) or intravenous (n = 5) routes. Patients not undergoing opiate withdrawal evinced increased baseline pain tolerance latencies prior to drug administration compared with normal volunteers. Two patients undergoing the opiate withdrawal syndrome at the time of test experienced reduced pain tolerance latencies compared with normal volunteers, most probably corresponding to the hyperesthesia symptom of the syndrome. Intravenous morphine infusion (30 mg) induced a time-dependent increase in cutaneous pain tolerance with peak effect occurring 1-2 h after administration. This persisted for up to 4 h and thereafter declined. The time course of subjective pain self-report by visual pain analog scale (VPAS) measurements corresponded to the time course of increasing cutaneous pain tolerance latency assessed by dolorimetry. Pain self-reports following intrathecal morphine infusion (2.25 or 1 mg) followed a similar though slower onset to that reported by patients receiving intravenous morphine and was of lesser degree. In contrast, heat beam dolorimetric evidence of increased cutaneous pain tolerance (which was of lesser degree than following i.v. morphine) did not reach its maximum during the 4 h measuring period. A dissociation was noted therefore between the self-reported relief of endogenous pain and dolorimetrically measured cutaneous analgesia following intrathecal morphine administration. Linear regression correlation analysis characterized this phenomenon as a positive correlation between cutaneous pain tolerance and pain relief self-report following intravenous morphine infusion and a negative correlation following intrathecal administration. We propose that the phenomenon may be due to intrathecal morphine acting via two separate compartments: one spinal and one supraspinal.(ABSTRACT TRUNCATED AT 250 WORDS)
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