title: Involvement of spinal serotonin receptors in electroacupuncture anti-hyperalgesia in an inflammatory pain rat model.
abstract: We previously showed that electroacupuncture (EA) activates medulla-spinal serotonin-containing neurons. The present study investigated the effects of intrathecal 5,7-dihydroxytryptamine creatinine sulfate, a selective neurotoxin for serotonergic terminals, the 5-hydroxytryptamine 1A receptor (5-HT1AR) antagonist NAN-190 hydrobromide and the 5-HT2C receptor (5-HT2CR) antagonist SB-242,084 on EA anti-hyperalgesia. EA was given twice at acupoint GB30 after complete Freund's adjuvant (CFA) injection into hind paw. CFA-induced hyperalgesia was measured by assessing hind paw withdrawal latency (PWL) to a noxious thermal stimulus 30 min post-EA. Serotonin depletion and the 5-HT1AR antagonist blocked EA anti-hyperalgesia; the 5-HT2CR antagonist did not. Immunohistochemical staining showed that spinal 5-HT1AR was expressed and that 5-HT2CR was absent in naive and CFA-injected animals 2.5 h post-CFA. These results show a correlation between EA anti-hyperalgesia and receptor expression. Collectively, the data show that EA activates supraspinal serotonin neurons to release 5-HT, which acts on spinal 5-HT1AR to inhibit hyperalgesia.
authors.affiliation: Center for Integrative Medicine, School of Medicine, University of Maryland, 685 W Baltimore street, MSTF Rm 8-22, Baltimore, MD 21201, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Aihui
authors.initials: A
authors.lastname: Li
authors.forename: Jiajia
authors.initials: J
authors.lastname: Xin
authors.forename: Lixing
authors.initials: L
authors.lastname: Lao
authors.forename: Ke
authors.initials: K
authors.lastname: Ren
authors.forename: Brian M
authors.initials: BM
authors.lastname: Berman
authors.forename: Ming
authors.initials: M
authors.lastname: Tan
authors.forename: Rui-Xin
authors.initials: RX
authors.lastname: Zhang
mesh_terms: D015115:5,6-Dihydroxytryptamine / Q000031:analogs & derivatives / Q000494:pharmacology; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003404:Creatinine / Q000031:analogs & derivatives / Q000494:pharmacology; D015671:Electroacupuncture / Q000379:methods*; D006930:Hyperalgesia / Q000503:physiopathology / Q000628:therapy*; D007211:Indoles / Q000494:pharmacology; D007249:Inflammation / Q000503:physiopathology*; D008297:Male; D010146:Pain / Q000503:physiopathology*; D010879:Piperazines / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D059326:Serotonergic Neurons / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism
chemical_list: C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; D000631:Aminopyridines; D007211:Indoles; D010879:Piperazines; D044405:Receptor, Serotonin, 5-HT2C; D058829:Serotonin 5-HT1 Receptor Antagonists; D044282:Receptor, Serotonin, 5-HT1A; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; D012701:Serotonin; C078441:5,7-dihydroxytryptamine creatinine; D003404:Creatinine; D015115:5,6-Dihydroxytryptamine