Motor cortex stimulation for pain control induces changes in the endogenous opioid system

Background: Motor cortex stimulation (MCS) for neuropathic pain control induces focal cerebral blood flow changes involving regions with high density of opioid receptors. We studied the possible contribution of the endogenous opioid system to MCS-related pain relief. Methods: Changes in opioid receptor availability induced by MCS were studied with PET scan and [C-11] diprenorphine in eight patients with refractory neuropathic pain. Each patient underwent two preoperative (test-retest) PET scans and one postoperative PET scan acquired after 7 months of chronic MCS. Results: The two preoperative scans, performed at 2 weeks interval, did not show significant differences. Conversely, postoperative compared with preoperative PET scans revealed significant decreases of [C-11] diprenorphine binding in the anterior middle cingulate cortex (aMCC), peri-aqueductal gray (PAG), prefrontal cortex, and cerebellum. Binding changes in aMCC and PAG were significantly correlated with pain relief. Conclusion: The decrease in binding of the exogenous ligand was most likely explained by receptor occupancy due to enhanced secretion of endogenous opioids. Motor cortex stimulation (MCS) may thus induce release of endogenous opioids in brain structures involved in the processing of acute and chronic pain. Correlation of this effect with pain relief in at least two of these structures supports the role of the endogenous opioid system in pain control induced by MCS.