Rostral ventromedial medulla μ, but not κ, opioid receptors are involved in electroacupuncture anti-hyperalgesia in an inflammatory pain rat model

Abstract

It has been reported that intracerebroventricular injection of a μ receptor antagonist blocked 2 but not 100 Hz electroacupuncture (EA)-produced analgesia in an uninjured animal model. Because persistent pain changes neural response to external stimulation, we hypothesized that the mechanisms of EA anti-hyperalgesia may be different in persistent pain than in health. Hyperalgesia, decreased paw withdrawal latency (PWL) to a noxious thermal stimulus, was induced by subcutaneously injecting complete Freund’s adjuvant (CFA) into the hind paws of rats. Selective antagonists against μ (CTOP: D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-ThrNH2, 6.25 nmol) and κ (Nor-BIN: nor-binaltorphimine, 10 nmol) opioid receptors were infused into the rostral ventromedial medulla (RVM) 10 min before 30-min EA treatment at acupoint Huanti (GB30) 1 hr 30 min post-CFA. PWL was measured before and 2.5 post-CFA. Both 10 Hz and 100 Hz EA-produced anti-hyperalgesia were blocked by intra-RVM μ, but not κ, receptor antagonists. Double immunofluorescence staining demonstrated that μ receptor-containing neurons were GABAnergic and that GABAa receptor-containing neurons were serotonergic in the RVM. The results demonstrated an involvement of RVM μ, but not κ, receptors in EA-produced anti-hyperalgesia. In summary, EA may induce release of endogenous endomorphins that activate μ opioid receptors in GABAnergic neurons to suppress the release of GABA. This removes the tonic inhibition of GABA on serotonergic neurons in the RVM, and activation of these serotonergic neurons inhibits pain. EA may be used as complementary treatment for inflammatory pain.

Spatiotemporal changes of optical signals in the somatosensory cortex of neuropathic rats after electroacupuncture stimulation

“…EA stimulation reports showed the analgesic effects of EA in the brain [14, 30, 31]. After EA stimulation, higher levels of brain metabolism were observed in the middle temporal cortex, orbital frontal cortex, insula, middle frontal gyrus, angular gyrus, post-cingulate cortex, precuneus, and middle cingulate cortex [30].…”

“…EA stimulation primarily induces activity in the somatosensory related region, including those in the inferior parietal lobule; secondary somatosensory cortex; insular cortex; and thalamus, except for the superior temporal gyrus [31]. Moreover, EA inhibition of hyperalgesia is involved in the release of mu and delta receptor agonists [32].…”

Effect of transcutaneous acupoint electrical stimulation on propofol sedation: an electroencephalogram analysis of patients undergoing pituitary adenomas resection

“…Elevated endogenous GABA levels could cause the elevation of beta power [ 41 , 42 ]. Electro acupuncture may induce release of endogenous endomorphins that activate μ opioid receptors in GABA-nergic neurons to suppress the release of GABA [ 43 ]. Taken together, it is conceivable that the decreased power of beta oscillations in our results might reflect the inhibition of GABAergic interneurons by TAES.…”

Mechanisms of Acupuncture–Electroacupuncture on Persistent Pain

“…Selective μ but not κ receptor antagonists infused into the rostral ventromedial medulla (RVM) blocked 10 and 100 Hz electroacupuncture-produced antihyperalgesia assessed with PWL. 117 Double immunofluorescence staining demonstrated that μ receptor-containing neurons are GABAnergic and that GABAa receptor-containing neurons are serotonergic in the RVM. 117 Hence, electroacupuncture induces release of endogenous endomorphins.…”

“…117 Double immunofluorescence staining demonstrated that μ receptor-containing neurons are GABAnergic and that GABAa receptor-containing neurons are serotonergic in the RVM. 117 Hence, electroacupuncture induces release of endogenous endomorphins. These activate μ opioid receptors in GABAnergic neurons that suppress GABA release.…”