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5-HT2C receptor agonists attenuate pain-related behaviour in a rat model of trigeminal neuropathic pain.
Eur J Pain. 2010 Nov; 14(10):999-1006.EJ

Abstract

Peripheral branches of the trigeminal nerve may be damaged during maxillofacial injury or surgical procedures and trigeminal trauma may induce severe pain that is very challenging to treat. Chronic constriction injury to the infraorbital nerve (ION-CCI) by loose ligatures has proven a useful model for some types of trigeminal neuropathic pain disorder. Using ION-CCI rats, we examined the antiallodynic effects of intrathecally administered agents which are selective for 5-HT2C receptors. Allodynia was evaluated by applying von Frey filaments to skin innervated by the injured ION. Dose-dependent antiallodynic effects followed administration of three 5-HT2C receptor agonists, 6-chloro-2-(1-piperazinyl)-pyrazine (MK212: 10, 30, and 100 μg); (S)-2-(chloro-5-fluoro-indol-l-yl)-1-methyamine fumarate (RO 60-0175: 10, 30, and 100 μg); (AaR)-8,9-dichloro-2,3,4,4a-tetrahydro-1H-pyrazino[1,2-a]quinoxalin-5(6H)-one (WAY-161503: 10, 30, and 100 μg). ED50 values for antiallodynic effects of MK212, RO 60-0175, and WAY-161503 were 39.62, 46.67, and 51.22 μg, respectively. Intrathecal administration of the 5-HT2C receptor antagonist, 8-[5-2,4-dimethoxy-5-(4-trifluoromethylphenylsulphonamido)phenyl-5-oxopentyl]-1,3,8-triazaspiro[4,5]decane-2,4-dione (RS-102221: 30 μg) did not alter the mechanical threshold. Intrathecal pretreatment with RS-102221 (10 and 30 μg) reduced the antiallodynic effects of the highest dose of 5-HT2C agonists. These results indicated that, in this rat model, the 5-HT2C receptor plays a role in spinal inhibition of trigeminal neuropathic pain.

Authors+Show Affiliations

Department of Plastic & Reconstructive Surgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan. ckadn610@sutv.zaq.ne.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

20488736

Citation

Nakai, Kunihiro, et al. "5-HT2C Receptor Agonists Attenuate Pain-related Behaviour in a Rat Model of Trigeminal Neuropathic Pain." European Journal of Pain (London, England), vol. 14, no. 10, 2010, pp. 999-1006.
Nakai K, Nakae A, Oba S, et al. 5-HT2C receptor agonists attenuate pain-related behaviour in a rat model of trigeminal neuropathic pain. Eur J Pain. 2010;14(10):999-1006.
Nakai, K., Nakae, A., Oba, S., Mashimo, T., & Ueda, K. (2010). 5-HT2C receptor agonists attenuate pain-related behaviour in a rat model of trigeminal neuropathic pain. European Journal of Pain (London, England), 14(10), 999-1006. https://doi.org/10.1016/j.ejpain.2010.04.008
Nakai K, et al. 5-HT2C Receptor Agonists Attenuate Pain-related Behaviour in a Rat Model of Trigeminal Neuropathic Pain. Eur J Pain. 2010;14(10):999-1006. PubMed PMID: 20488736.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 5-HT2C receptor agonists attenuate pain-related behaviour in a rat model of trigeminal neuropathic pain. AU - Nakai,Kunihiro, AU - Nakae,Aya, AU - Oba,Sosuke, AU - Mashimo,Takashi, AU - Ueda,Koichi, Y1 - 2010/05/21/ PY - 2010/01/09/received PY - 2010/03/19/revised PY - 2010/04/14/accepted PY - 2010/5/22/entrez PY - 2010/5/22/pubmed PY - 2011/3/5/medline SP - 999 EP - 1006 JF - European journal of pain (London, England) JO - Eur J Pain VL - 14 IS - 10 N2 - Peripheral branches of the trigeminal nerve may be damaged during maxillofacial injury or surgical procedures and trigeminal trauma may induce severe pain that is very challenging to treat. Chronic constriction injury to the infraorbital nerve (ION-CCI) by loose ligatures has proven a useful model for some types of trigeminal neuropathic pain disorder. Using ION-CCI rats, we examined the antiallodynic effects of intrathecally administered agents which are selective for 5-HT2C receptors. Allodynia was evaluated by applying von Frey filaments to skin innervated by the injured ION. Dose-dependent antiallodynic effects followed administration of three 5-HT2C receptor agonists, 6-chloro-2-(1-piperazinyl)-pyrazine (MK212: 10, 30, and 100 μg); (S)-2-(chloro-5-fluoro-indol-l-yl)-1-methyamine fumarate (RO 60-0175: 10, 30, and 100 μg); (AaR)-8,9-dichloro-2,3,4,4a-tetrahydro-1H-pyrazino[1,2-a]quinoxalin-5(6H)-one (WAY-161503: 10, 30, and 100 μg). ED50 values for antiallodynic effects of MK212, RO 60-0175, and WAY-161503 were 39.62, 46.67, and 51.22 μg, respectively. Intrathecal administration of the 5-HT2C receptor antagonist, 8-[5-2,4-dimethoxy-5-(4-trifluoromethylphenylsulphonamido)phenyl-5-oxopentyl]-1,3,8-triazaspiro[4,5]decane-2,4-dione (RS-102221: 30 μg) did not alter the mechanical threshold. Intrathecal pretreatment with RS-102221 (10 and 30 μg) reduced the antiallodynic effects of the highest dose of 5-HT2C agonists. These results indicated that, in this rat model, the 5-HT2C receptor plays a role in spinal inhibition of trigeminal neuropathic pain. SN - 1532-2149 UR - https://www.unboundmedicine.com/medline/citation/20488736/5_HT2C_receptor_agonists_attenuate_pain_related_behaviour_in_a_rat_model_of_trigeminal_neuropathic_pain_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1090-3801(10)00100-X DB - PRIME DP - Unbound Medicine ER -