Role of Presynaptic Muscarinic and GABAB Receptors in Spinal Glutamate Release and Cholinergic Analgesia in Rats

作者：De‐Pei Li, Shaorui Chen, Yu‐Zhen Pan, Allan I. Levey, Hui‐Lin Pan · 发表于：The Journal of Physiology · 年份：2002 · DOI：10.1113/jphysiol.2002.020644 · 被引用次数：154 · 研究领域：Pain Mechanisms and Treatments、Ion channel regulation and function、Neuroscience and Neuropharmacology Research

Spinally administered muscarinic receptor agonists or acetylcholinesterase inhibitors can produce effective pain relief. However, the analgesic mechanisms and the site of actions of cholinergic agents in the spinal cord are not fully understood. In this study, we investigated the mechanisms underlying cholinergic presynaptic regulation of glutamate release onto spinal dorsal horn neurons. The role of spinal GABA(B) receptors in the antinociceptive action of muscarine was also determined. Whole-cell voltage-clamp recordings were performed on visualized dorsal horn neurons in the lamina II in the spinal cord slice preparation of rats. The miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs) were recorded in the presence of tetrodotoxin. The evoked EPSCs (eEPSCs) were obtained by electrical stimulation of the dorsal root entry zone or the attached dorsal root. Nociception in rats was measured using a radiant heat stimulus and the effect of intrathecal administration of drugs tested. Acetylcholine (10-100 microM) reduced the amplitude of monosynaptic eEPSCs in a concentration-dependent manner. Acetylcholine also significantly decreased the frequency of non-NMDA receptor-mediated mEPSCs, which was antagonized by atropine but not mecamylamine. The frequency of GABA(A) receptor-mediated mIPSCs was significantly increased by acetylcholine and this excitatory effect was abolished by atropine. Existence of presynaptic M(2) muscarin...