title: 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 100Hz 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 a 30-min EA treatment at acupoint Huantiao (GB30) 1h 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.
authors.affiliation: Center for Integrative Medicine, School of Medicine, University of Maryland, Baltimore, MD 21201, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Aihui
authors.initials: A
authors.lastname: Li
authors.forename: Lixing
authors.initials: L
authors.lastname: Lao
authors.forename: Jiajia
authors.initials: J
authors.lastname: Xin
authors.forename: Ke
authors.initials: K
authors.lastname: Ren
authors.forename: Brian M
authors.initials: BM
authors.lastname: Berman
authors.forename: Rui-Xin
authors.initials: RX
authors.lastname: Zhang
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015671:Electroacupuncture / Q000379:methods*; D005620:Freund's Adjuvant / Q000008:administration & dosage / Q000633:toxicity; D006930:Hyperalgesia / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D020078:Neurogenic Inflammation / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D005620:Freund's Adjuvant