Institute of Neuroscience and State Key Laboratory of Neuroscience, Chinese Academy of Sciences, Shanghai 200031, People's Republic of China.
Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):13117-22. doi: 10.1073/pnas.1008382107. Epub 2010 Jul 6.
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.
吗啡诱导的镇痛和抗伤害性耐受被认为是通过疼痛通路中 δ 型阿片受体（DORs）和 μ 型阿片受体（MORs）之间的相互作用来调节的。然而，最近有证据表明，DORs 在背根神经节（DRG）中的伤害性小直径神经元中表达，并且 DORs 与 MORs 和神经肽共存。我们现在使用原位杂交、单细胞 PCR 和免疫染色报告，DOR 不仅广泛表达于大 DRG 神经元中，而且也表达于小 DRG 神经元中，并且与肽能小 DRG 神经元中的 MOR 共存，其在大致密核心囊泡中的定位依赖于原促甲状腺素原。重要的是，DOR 和 MOR 激动剂均可减少单个小 DRG 神经元中去极化诱导的 Ca2+电流，并抑制背根脊髓中的传入 C 纤维突触传递。因此，小 DRG 神经元中 DORs 和 MORs 的共存是阿片受体在调节伤害性传入传递和阿片类镇痛中的直接相互作用的基础。
