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Possible involvement of spinal noradrenergic mechanisms in the antiallodynic effect of intrathecally administered 5-HT2C receptor agonists in the rats with peripheral nerve injury.
Eur J Pharmacol. 2007 Jul 12; 567(1-2):89-94.EJ

Abstract

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 microg) and 1-(m-chlorophenyl)-piperazine (mCPP; 300 microg) 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 microg), 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.

Authors+Show Affiliations

Department of Anesthesiology, Gunma University Graduate School of Medicine, 3-39-22, Showa, Maebashi, Gunma, 371-0801 Japan. hobata@showa.gunma-u.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17451674

Citation

Obata, Hideaki, et al. "Possible Involvement of Spinal Noradrenergic Mechanisms in the Antiallodynic Effect of Intrathecally Administered 5-HT2C Receptor Agonists in the Rats With Peripheral Nerve Injury." European Journal of Pharmacology, vol. 567, no. 1-2, 2007, pp. 89-94.
Obata H, Ito N, Sasaki M, et al. Possible involvement of spinal noradrenergic mechanisms in the antiallodynic effect of intrathecally administered 5-HT2C receptor agonists in the rats with peripheral nerve injury. Eur J Pharmacol. 2007;567(1-2):89-94.
Obata, H., Ito, N., Sasaki, M., Saito, S., & Goto, F. (2007). Possible involvement of spinal noradrenergic mechanisms in the antiallodynic effect of intrathecally administered 5-HT2C receptor agonists in the rats with peripheral nerve injury. European Journal of Pharmacology, 567(1-2), 89-94.
Obata H, et al. Possible Involvement of Spinal Noradrenergic Mechanisms in the Antiallodynic Effect of Intrathecally Administered 5-HT2C Receptor Agonists in the Rats With Peripheral Nerve Injury. Eur J Pharmacol. 2007 Jul 12;567(1-2):89-94. PubMed PMID: 17451674.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Possible involvement of spinal noradrenergic mechanisms in the antiallodynic effect of intrathecally administered 5-HT2C receptor agonists in the rats with peripheral nerve injury. AU - Obata,Hideaki, AU - Ito,Naomi, AU - Sasaki,Masayuki, AU - Saito,Shigeru, AU - Goto,Fumio, Y1 - 2007/03/30/ PY - 2006/04/11/received PY - 2007/02/21/revised PY - 2007/03/19/accepted PY - 2007/4/25/pubmed PY - 2007/7/28/medline PY - 2007/4/25/entrez SP - 89 EP - 94 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 567 IS - 1-2 N2 - 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 microg) and 1-(m-chlorophenyl)-piperazine (mCPP; 300 microg) 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 microg), 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. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/17451674/Possible_involvement_of_spinal_noradrenergic_mechanisms_in_the_antiallodynic_effect_of_intrathecally_administered_5_HT2C_receptor_agonists_in_the_rats_with_peripheral_nerve_injury_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(07)00385-8 DB - PRIME DP - Unbound Medicine ER -