2001 Fiscal Year Final Research Report Summary
The mechanism of 5-HT receptor agonists for inhibitory effect in neuropathic pain
| Project/Area Number |
12671451
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Gunma University |
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Principal Investigator |
OBATA Hideaki School of Medicine, Gunma University Instructor, 医学部, 助手 (20302482)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Neuropathic pain / Serotonin / Allodynia / Intrathecally administration / 5-HT_2 receptor agonists / Muscarinic receptor antagonists |
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| Research Abstract |
Several lines of evidence demonstrated that bulbospinal serotonergic (5-HT) systems mediate suppression of nociceptive input to spinal dorsal horn. Intrathecally administered 5-HT has antinociceptive effects in acute pain models in animals. Autoradiographic studies have revealed that the presence of several 5-HT receptors in the spinal cord. Although some controversy persists, 5-HT_<1A>, 5-HT_<1B>, 5-HT_2, 5-HT_3 receptor subtypes have been reported to contribute to the antinociceptive action of 5-HT in the spinal cord. However, whether activation of these spinal 5-HT receptor subtypes inhibits neuropathic pain is unknown. It has been reported that tight ligation of spinal nerves L5 and L6 lead to allodynia. We used various agonists and antagonists to compare antiallodynic actions at each spinal 5-HT receptor subtypes in this rat model of allodynia, and found that only intrathecally administered 5-HT_2 receptor agonists produced antiallodynic action (Pain 2001 ; 90 : 173-179). Further, we examined the mechanisms of antiallodynic effect of intrathecally administered 5-HT_2 receptor agonists. It has been reported that 5-HT regulates several neurotransmitters, such as acetylcholine, noradrenaline, GABA, or adenosine, in central nervous system. Therefore, we investigated the possible involvement of other associated spinal receptor systems with respect to the antiallodynic action of a 5-HT_2 receptors agonist. From these experiments, we found that muscarinic receptor antagonists reversed the antiallodynic effects of intrathecally administered 5-HT_2 receptor agonists (Brain Res, In Press). Acetylcholine release and muscarinic receptor activation in the spinal cord appears to be, at least in part, involved in the antiallodynic action of an intrathecally administered 5-HT_2 receptor agonists.
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