Coexpression of delta- and mu-opioid receptors in nociceptive sensory neurons.
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.
Wang
Hai-Bo
HB
Institute of Neuroscience and State Key Laboratory of Neuroscience, Chinese Academy of Sciences, Shanghai 200031, People's Republic of China.
Zhao
Bo
B
Zhong
Yan-Qing
YQ
Li
Kai-Cheng
KC
Li
Zi-Yan
ZY
Wang
Qiong
Q
Lu
Yin-Jing
YJ
Zhang
Zhen-Ning
ZN
He
Shao-Qiu
SQ
Zheng
Han-Cheng
HC
Wu
Sheng-Xi
SX
Hökfelt
Tomas G M
TG
Bao
Lan
L
Zhang
Xu
X
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
D010455:Peptides; D011498:Protein Precursors; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D015320:Tachykinins; C054618:protachykinin