Coexpression of δ- and μ-opioid receptors in nociceptive sensory neurons

Hai Bo Wang, Bo Zhao, Yan Qing Zhonga, Kai Cheng Li, Zi Yan Li, Qiong Wang, Yin Jing Lu, Zhen Ning Zhang, Shao Qiu He, Han Cheng Zheng, Sheng Xi Wu, Tomas G.M. Hökfelt, Lan Bao, Xu Zhang

Research output: Contribution to journalArticlepeer-review


Morphine-induced analgesia and antinociceptive tolerance are known to be modulated by interaction between δ-opioid receptors (DORs) and μ-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 Ca2+ 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.

Original languageEnglish (US)
Pages (from-to)13117-13122
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number29
StatePublished - Jul 20 2010
Externally publishedYes


  • Dorsal root ganglion
  • Pain
  • Peptides
  • Spinal cord
  • Tolerance

ASJC Scopus subject areas

  • General

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