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Activation of muscarinic receptors inhibits spinal dorsal horn projection neurons: role of GABAB receptors.
Neuroscience. 2004; 125(1):141-8.N

Abstract

Spinally administered muscarinic receptor agonists or acetylcholinesterase inhibitors produce efficacious analgesia. However, the mechanisms of the antinociceptive actions of muscarinic agonists in the spinal cord are not fully known. Previous in vitro studies have shown that muscarinic agonists increase GABA release and reduce the glutamatergic synaptic input to lamina II interneurons through GABAB receptors in the spinal cord. In the present study, we studied the effect of muscarinic agents on dorsal horn projection neurons and the role of spinal GABAB receptors in their action. Single-unit activity of ascending dorsal horn neurons was recorded in the lumbar spinal cord of anesthetized rats. The responses of dorsal horn neurons to graded mechanical stimuli were determined before and after topical spinal application of muscarine and neostigmine. We found that topical application of 0.1-5 microM muscarine or 0.5-5 microM neostigmine significantly suppressed the evoked response of dorsal horn neurons in a concentration-dependent manner. The inhibitory effect of muscarine or neostigmine on dorsal horn neurons was completely abolished in the presence of 1 microM atropine and by intrathecal pretreatment with 1 microg pertussis toxin to inactivate inhibitory G proteins. Furthermore, the inhibitory effect of both muscarine and neostigmine on the evoked response of dorsal horn neurons was significantly attenuated in the presence of 1 microM CGP55845, a GABAB receptor antagonist. Collectively, these data suggest that muscarinic agents inhibit dorsal horn projection neurons through muscarinic receptors coupled to pertussis toxin-sensitive Gi/o proteins. The inhibitory action of muscarinic agonists on these dorsal horn neurons is mediated in part by spinal GABAB receptors.

Authors+Show Affiliations

Department of Anesthesiology, H187, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033-0850, USA.No affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15051153

Citation

Chen, S-R, and H-L Pan. "Activation of Muscarinic Receptors Inhibits Spinal Dorsal Horn Projection Neurons: Role of GABAB Receptors." Neuroscience, vol. 125, no. 1, 2004, pp. 141-8.
Chen SR, Pan HL. Activation of muscarinic receptors inhibits spinal dorsal horn projection neurons: role of GABAB receptors. Neuroscience. 2004;125(1):141-8.
Chen, S. R., & Pan, H. L. (2004). Activation of muscarinic receptors inhibits spinal dorsal horn projection neurons: role of GABAB receptors. Neuroscience, 125(1), 141-8.
Chen SR, Pan HL. Activation of Muscarinic Receptors Inhibits Spinal Dorsal Horn Projection Neurons: Role of GABAB Receptors. Neuroscience. 2004;125(1):141-8. PubMed PMID: 15051153.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of muscarinic receptors inhibits spinal dorsal horn projection neurons: role of GABAB receptors. AU - Chen,S-R, AU - Pan,H-L, PY - 2004/01/21/accepted PY - 2004/3/31/pubmed PY - 2004/6/4/medline PY - 2004/3/31/entrez SP - 141 EP - 8 JF - Neuroscience JO - Neuroscience VL - 125 IS - 1 N2 - Spinally administered muscarinic receptor agonists or acetylcholinesterase inhibitors produce efficacious analgesia. However, the mechanisms of the antinociceptive actions of muscarinic agonists in the spinal cord are not fully known. Previous in vitro studies have shown that muscarinic agonists increase GABA release and reduce the glutamatergic synaptic input to lamina II interneurons through GABAB receptors in the spinal cord. In the present study, we studied the effect of muscarinic agents on dorsal horn projection neurons and the role of spinal GABAB receptors in their action. Single-unit activity of ascending dorsal horn neurons was recorded in the lumbar spinal cord of anesthetized rats. The responses of dorsal horn neurons to graded mechanical stimuli were determined before and after topical spinal application of muscarine and neostigmine. We found that topical application of 0.1-5 microM muscarine or 0.5-5 microM neostigmine significantly suppressed the evoked response of dorsal horn neurons in a concentration-dependent manner. The inhibitory effect of muscarine or neostigmine on dorsal horn neurons was completely abolished in the presence of 1 microM atropine and by intrathecal pretreatment with 1 microg pertussis toxin to inactivate inhibitory G proteins. Furthermore, the inhibitory effect of both muscarine and neostigmine on the evoked response of dorsal horn neurons was significantly attenuated in the presence of 1 microM CGP55845, a GABAB receptor antagonist. Collectively, these data suggest that muscarinic agents inhibit dorsal horn projection neurons through muscarinic receptors coupled to pertussis toxin-sensitive Gi/o proteins. The inhibitory action of muscarinic agonists on these dorsal horn neurons is mediated in part by spinal GABAB receptors. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/15051153/Activation_of_muscarinic_receptors_inhibits_spinal_dorsal_horn_projection_neurons:_role_of_GABAB_receptors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306452204000521 DB - PRIME DP - Unbound Medicine ER -