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; Zhao, Bo; Zhong, Yan-Qing; Li, Kai-Cheng; Li, Zi-Yan; Wang, Qiong; Lu, Yin-Jing; Zhang, Zhen-Ning; He, Shao-Qiu; Zheng, Han-Cheng; Wu, Sheng-Xi; Hokfelt, Tomas G. M.; Bao, Lan; Zhang, Xu.Coexpression of delta- and mu-opioid receptors in nociceptive sensory neurons,PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2010,107(29):13117-13122