Department of Oral and Maxillofacial Surgery, University of California, San Francisco, CA 94143-0440, USA.
Exp Neurol. 2011 Jun;229(2):502-6. doi: 10.1016/j.expneurol.2011.03.021. Epub 2011 Mar 31.
We have previously demonstrated an opioid link in nucleus accumbens (NAc) that mediates antinociception produced by a novel ascending pain modulation pathway. For example, noxious stimulation induces heterosegmental antinociception that is mediated by both mu- and delta-opioid receptors in NAc. However, spinal intrathecal administration of the mu-receptor agonist [D-Ala(2), N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO) also induces heterosegmental antinociception. The aim of the present study in the rat was to identify the intra-NAc opioid receptors that mediate the antinociceptive effects of spinally administered DAMGO and also to determine the effect of NAc efferent activity on nociception. Intra-NAc administration of either the mu-opioid receptor antagonist Cys(2),Tyr(3), Orn(5),Pen(7)amide (CTOP) or the delta-opioid receptor antagonist naltrindole blocked the antinociceptive effect of spinally administered DAMGO on the jaw-opening reflex (JOR). Injection of quaternary lidocaine (QX-314) attenuated the JOR, suggesting that the output of NAc is pronociceptive. In support of this, intra-NAc injection of the excitatory amino acid agonist kainate enhanced the JOR. Thus, it is possible to modulate activity in NAc to bidirectionally attenuate or enhance nociception, suggesting a potential role for NAc in setting nociceptive sensitivity.
我们之前已经证明了中脑腹侧被盖区（NAc）中的阿片类物质在介导由新的上行疼痛调制途径产生的镇痛作用中的作用。例如，伤害性刺激诱导异节段镇痛，该镇痛由 NAc 中的μ-和δ-阿片受体介导。然而，脊髓鞘内给予μ-受体激动剂[D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin（DAMGO）也会诱导异节段镇痛。本研究的目的是在大鼠中确定介导脊髓给予 DAMGO 的镇痛作用的 NAc 内阿片受体，并确定 NAc 传出活动对伤害感受的影响。NAc 内给予μ-阿片受体拮抗剂 Cys(2),Tyr(3),Orn(5),Pen(7)amide (CTOP)或δ-阿片受体拮抗剂naltrindole 可阻断脊髓给予 DAMGO 对张口反射（JOR）的镇痛作用。注射季铵型利多卡因（QX-314）减弱了 JOR，表明 NAc 的输出具有致痛作用。支持这一观点的是，NAc 内注射兴奋性氨基酸激动剂海人藻酸增强了 JOR。因此，可以调节 NAc 的活动，从而双向减弱或增强伤害感受，这表明 NAc 在设定伤害感受敏感性方面可能具有潜在作用。
