RGD Reference Report - Possible involvement of spinal noradrenergic mechanisms in the antiallodynic effect of intrathecally administered 5-HT(2C) receptor agonists in the rats with peripheral nerve injury.

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Possible involvement of spinal noradrenergic mechanisms in the antiallodynic effect of intrathecally administered 5-HT(2C) receptor agonists in the rats with peripheral nerve injury.
Authors:	Obata, H Ito, N Sasaki, M Saito, S Goto, F
Citation:	Obata H, etal., Eur J Pharmacol. 2007 Mar 30;.
RGD ID:	1624996
Pubmed:	PMID:17451674 (View Abstract at PubMed)
DOI:	DOI:10.1016/j.ejphar.2007.03.029 (Journal Full-text)
Intrathecal administration of serotonin type 2C (5-HT(2C)) receptor agonists produces an antiallodynic effect in a rat model of neuropathic pain. In the present study, we characterized this effect pharmacologically. Allodynia was produced by tight ligation of the fifth (L5) and sixth (L6) lumbar spinal nerves on the left side, and was measured by applying von Frey filaments to the left hindpaw. 6-chloro-2-(1-piperazinyl)-pyrazine (MK212; 100 mug) and 1-(m-chlorophenyl)-piperazine (mCPP; 300 mug) were used as 5-HT(2C) receptor agonists. Intrathecal administration of these agonists resulted in an antiallodynic effect. Intrathecal administration of atropine (30 mug), a muscarinic receptor antagonist, and yohimbine (30 mug), an alpha(2)-adrenoceptor antagonist, reversed the effects of 5-HT(2C) receptor agonists. Intrathecal pretreatment with 6-hydroxydopamine, an adrenergic neurotoxin, inhibited the antiallodynic effect of MK212. These results suggest that spinal noradrenergic mechanisms are involved in the antiallodynic effects of intrathecally administered 5-HT(2C) receptor agonists. Previously, we demonstrated that intrathecal administration of 5-HT(2A) receptor agonists also produced antiallodynic effects, and the effects were not reversed by yohimbine. Taken together, these findings suggest that 5-HT(2A) and 5-HT(2C) receptors in the dorsal horn of the spinal cord might be involved in alleviating neuropathic pain by different mechanisms.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
HTR2C	Human	Pain		ISO	Htr2c (Rattus norvegicus)		RGD
Htr2c	Rat	Pain		IDA			RGD
Htr2c	Mouse	Pain		ISO	Htr2c (Rattus norvegicus)		RGD

Objects Annotated

Genes (Rattus norvegicus)

Htr2c (5-hydroxytryptamine receptor 2C)

Genes (Mus musculus)

Htr2c (5-hydroxytryptamine (serotonin) receptor 2C)

Genes (Homo sapiens)

HTR2C (5-hydroxytryptamine receptor 2C)

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Possible involvement of spinal noradrenergic mechanisms in the antiallodynic effect of intrathecally administered 5-HT(2C) receptor agonists in the rats with peripheral nerve injury.