title: Exacerbated mechanical hyperalgesia in rats with genetically predisposed depressive behavior: role of melatonin and NMDA receptors.
abstract: A connection between pain and depression has long been recognized in the clinical setting; however, its mechanism remains unclear. This study showed that mechanical hyperalgesia induced by unilateral temporomandibular joint (TMJ) inflammation was exacerbated in Wistar-Kyoto (WKY) rats with genetically predisposed depressive behavior. Reciprocally, TMJ inflammation enhanced depressive behavior such that a lower nociceptive threshold correlated with a higher score of depressive behavior in the same WKY rats. As compared with Wistar rats, WKY rats showed a lower plasma melatonin level, downregulation of the melatonin MT1 receptor, but upregulation of the NR1 subunit of the NMDA receptor in the ipsilateral trigeminal subnucleus caudalis (Sp5C). Intracisternal administration of 6-chloromelatonin (250 μg, twice daily for 7 days) concurrently attenuated mechanical hyperalgesia and depressive behavior in WKY rats as well as downregulated the NR1 expression in the ipsilateral Sp5C. In patch-clamp recordings, melatonin dose-dependently decreased NMDA-induced currents in spinal cord dorsal horn substantia gelatinosa neurons. These results demonstrate a reciprocal relationship between TMJ inflammation-induced mechanical hyperalgesia and depressive behavior and suggest that the central melatoninergic system, through modulation of the NMDA receptor expression and activity, may play a role in the mechanisms of the comorbidity between pain and depression.
authors.affiliation: MGH Center for Translational Pain Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Department of Physiology, Southern Medical University, Guangzhou, China Department of Anesthesia, West China Hospital, Sichuan University, Chengdu, Sichuan, China Center for TMD and Orofacial Pain, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Shuxing
authors.initials: S
authors.lastname: Wang
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Tian
authors.forename: Li
authors.initials: L
authors.lastname: Song
authors.forename: Grewo
authors.initials: G
authors.lastname: Lim
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Tan
authors.forename: Zerong
authors.initials: Z
authors.lastname: You
authors.forename: Lucy
authors.initials: L
authors.lastname: Chen
authors.forename: Jianren
authors.initials: J
authors.lastname: Mao
mesh_terms: D000818:Animals; D003866:Depressive Disorder / Q000150:complications* / Q000503:physiopathology*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006930:Hyperalgesia / Q000150:complications* / Q000503:physiopathology*; D008297:Male; D051381:Rats; D011921:Rats, Inbred WKY; D044094:Receptors, Melatonin / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D014110:Touch
chemical_list: D044094:Receptors, Melatonin; D016194:Receptors, N-Methyl-D-Aspartate