title: Coexpression of delta- and mu-opioid receptors in nociceptive sensory neurons.
abstract: Morphine-induced analgesia and antinociceptive tolerance are known to be modulated by interaction between delta-opioid receptors (DORs) and mu-opioid receptors (MORs) in the pain pathway. However, evidence for expression of DORs in nociceptive small-diameter neurons in dorsal root ganglia (DRG) and for coexistence of DORs with MORs and neuropeptides has recently been challenged. We now report, using in situ hybridization, single-cell PCR, and immunostaining, that DORs are widely expressed not only in large DRG neurons but in small ones and coexist with MORs in peptidergic small DRG neurons, with protachykinin-dependent localization in large dense-core vesicles. Importantly, both DOR and MOR agonists reduce depolarization-induced Ca(2+) currents in single small DRG neurons and inhibit afferent C-fiber synaptic transmission in the dorsal spinal cord. Thus, coexistence of DORs and MORs in small DRG neurons is a basis for direct interaction of opioid receptors in modulation of nociceptive afferent transmission and opioid analgesia.
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Chinese Academy of Sciences, Shanghai 200031, People's Republic of China.
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Zhao
authors.forename: Yan-Qing
authors.initials: YQ
authors.lastname: Zhong
authors.forename: Kai-Cheng
authors.initials: KC
authors.lastname: Li
authors.forename: Zi-Yan
authors.initials: ZY
authors.lastname: Li
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wang
authors.forename: Yin-Jing
authors.initials: YJ
authors.lastname: Lu
authors.forename: Zhen-Ning
authors.initials: ZN
authors.lastname: Zhang
authors.forename: Shao-Qiu
authors.initials: SQ
authors.lastname: He
authors.forename: Han-Cheng
authors.initials: HC
authors.lastname: Zheng
authors.forename: Sheng-Xi
authors.initials: SX
authors.lastname: Wu
authors.forename: Tomas G M
authors.initials: TG
authors.lastname: Hökfelt
authors.forename: Lan
authors.initials: L
authors.lastname: Bao
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D009619:Nociceptors / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D011498:Protein Precursors / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017465:Receptors, Opioid, delta / Q000235:genetics / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000378:metabolism*; D022142:Secretory Vesicles / Q000187:drug effects / Q000378:metabolism; D015320:Tachykinins / Q000494:pharmacology
chemical_list: D010455:Peptides; D011498:Protein Precursors; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D015320:Tachykinins; C054618:protachykinin