Role of presynaptic muscarinic and XXXX (B) receptors in spinal @entity2227 release and cholinergic analgesia in @entity35 .

@entity2227 @entity1246 @entity7234 @entity1022 @entity6959 @entity143 @entity158 @entity3897 @entity35 @entity934
Spinally administered muscarinic receptor agonists or acetylcholinesterase inhibitors can produce effective @entity158 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 @entity2227 release onto spinal dorsal horn neurons. The role of spinal @entity1246 (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 @entity35 . The miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs) were recorded in the presence of @entity1022 . The evoked EPSCs (eEPSCs) were obtained by electrical stimulation of the dorsal root entry zone or the attached dorsal root. Nociception in @entity35 was measured using a radiant heat stimulus and the effect of intrathecal administration of drugs tested. @entity934 (10-100 microM) reduced the amplitude of monosynaptic eEPSCs in a concentration-dependent manner. @entity934 also significantly decreased the frequency of non- @entity143 receptor-mediated mEPSCs, which was antagonized by @entity3897 but not @entity6959 . The frequency of @entity1246 (A) receptor-mediated mIPSCs was significantly increased by @entity934 and this excitatory effect was abolished by @entity3897 . Existence of presynaptic M(2) muscarinic receptors in the spinal dorsal horn was further demonstrated by immunocytochemistry staining and dorsal rhizotomy. @entity7234 , a @entity1246 (B) receptor antagonist, significantly attenuated the inhibitory effect of @entity934 on the frequency of mEPSCs and the amplitude of monosynaptic eEPSCs in lamina II neurons. Furthermore, the antinociceptive action produced by intrathecal muscarine was significantly reduced by @entity7234 pretreatment in @entity35 . Therefore, data from this integrated study provide new information that @entity934 inhibits the glutamatergic synaptic input to lamina II neurons through presynaptic muscarinic receptors. Inhibition of @entity2227 release onto lamina II neurons by presynaptic muscarinic and @entity1246 (B) heteroreceptors in the spinal cord probably contributes to the antinociceptive action of cholinergic agents.
