<p>Impulses coming from peripheries are modified in the spinal cord and transmitted to the brain. Several neurotransmitters have been involved in the processing of impulses in the spinal dorsal horn. Acetylcholine (ACh) is one of many neurotransmitters involved in the regulation of nociception in the spinal cord. In this study we investigated the role of nicotinic, muscarinic, serotonergic and GABA receptors in the regulation of spinal ACh release since these receptors are reported to be involved in spinal nociceptive processes.</p><p>Different receptor ligands were infused intraspinally via microdialysis and the spinal ACh release was measured by on-line HPLC. Receptor-ligand binding studies were performed with spinal cord homogenates as well as receptors expressed in cells.</p><p>In the first study, we found that nicotine and some of the nicotinic antagonists used increased ACh release suggesting that spinal ACh release is regulated by different nAChRs. Nicotine and nicotinic agonists may act on different types of receptors with different affinity to produce the observed net effect of increased ACh release. We propose the possibility of an involvement of three different nicotinic receptor subtypes in the regulation of spinal ACh release. </p><p>The effect of epibatidine, which is regarded as a nicotinic agonist, on muscarinic receptors was investigated in the second study. We propose that epibatidine, in μM concentrations, is a partial muscarinic receptor agonist that may interact with spinal muscarinic receptors to increase ACh release. The dual action on both nAChRs and mAChRs may explain the potent analgesic effect observed after intra-spinal epibatidine administration.</p><p>In the third study, we investigated the role of serotonin receptor involvement in ACh release control. The results suggest that only 5-HT<sub>1A</sub> and 5-HT<sub>2A</sub> receptors are involved in spinal ACh release. Considering current knowledge, the most probable location of 5-HT<sub>2A</sub> receptors is on cholinergic neurones. On activation of the 5-HT<sub>2A</sub> receptors the cellular excitability of cholinergic neurones is increased which results in an increasing ACh release. The 5-HT<sub>1A</sub> receptors might be located on cell bodies of GABA neurones which inhibit the firing rate of the GABA neurones when activated by serotonin. </p><p>In the fourth study, we investigated the GABA receptor involvement in the regulation in spinal ACh release. We found that GABA<sub>A</sub> receptors are tonically inhibiting spinal ACh release. The results further suggest that GABA<sub>B</sub> receptors also are involved in the regulation of spinal ACh release. However, unlike GABA<sub>A</sub> antagonists, GABA<sub>B</sub> antagonists do not increase ACh release. This suggests that GABA<sub>B</sub> receptors are not tonically regulating the spinal ACh release. </p>
| Identifer | oai:union.ndltd.org:UPSALLA/oai:DiVA.org:uu-5931 |
| Date | January 2005 |
| Creators | Kommalage, Mahinda |
| Publisher | Uppsala University, Department of Neuroscience, Uppsala : Acta Universitatis Upsaliensis |
| Source Sets | DiVA Archive at Upsalla University |
| Language | English |
| Detected Language | English |
| Type | Doctoral thesis, comprehensive summary, text |
| Relation | Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 1651-6206 ; 70 |
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