Median nerve stimulation induces analgesia via orexin-initiated endocannabinoid disinhibition in the periaqueductal gray

• DOI: 10.1073/pnas.1807991115
• Publication Date: 2018-10-22T19:16:04Z
• Authors: Yi-Hung Chen; Hsin-Jung Lee; Ming Tatt Lee; Ya-Ting Wu; Yen-Hsien Lee; Ling-Ling Hwang; Ming-Shiu Hung; Andreas Zimmer; Ken Mackie; Lih-Chu Chiou
• Keywords: Periaqueductal gray; Endogenous opioid; Disinhibition; Rimonabant; Orexin-A

Significance Pain remains an unmet medical need due to the ineffectiveness or significant side effects of current pain therapies. Peripheral neurostimulation has been used relieve for decades, but its mechanism(s) remain unsettled. Here, we established animal model median nerve stimulation by electrically stimulating PC6 (Neiguan) acupoint mice (MNS-PC6). We found MNS-PC6 can release endogenous neuropeptide (orexin) from hypothalamus inhibit responses in through endocannabinoid (an lipid functioning like chemicals cannabis) that reduces inhibitory (GABAergic) control a midbrain pain-control region (the periaqueductal gray). Importantly, MNS-PC6–induced relief is opioid independent. Thus, may provide alternative strategy management opioid-tolerant patients.