Role of spinal 5-HT2 receptors subtypes in formalin-induced long-lasting hypersensitivity

Background the purpose of this study was to determine the role of spinal 5-ht2a,5-ht2b and 5-ht2c receptors in the development and maintenance of formalin-induced long-lasting secondary allodynia and hyperalgesia in rats,as well as their expression in the dorsal root ganglia (drg) during this process. methods 0.5-1% formalin was used to produce long-lasting secondary allodynia and hyperalgesia in rats. western blot was used to determine 5-ht2 receptors expression in drg. results formalin (0.5-1%) injection produced long-lasting (1-12 days) secondary allodynia and hyperalgesia in both ipsilateral and contralateral hind paws. intrathecal pre-treatment or post-treatment with the 5-ht2 receptor agonist,doi (1-10 nmol),increased 0.5% formalin-induced secondary allodynia and hyperalgesia in both paws. in contrast,intrathecal pre-treatment with the selective 5-ht2a (ketanserin 1-100 nmol),5-ht2b (rs 127445 1-100 nmol) or 5-ht2c (rs 102221 1-100 nmol) receptor antagonists prevented and reversed,respectively,1% formalin-induced secondary allodynia and hyperalgesia in both paws. likewise,the pronociceptive effect of doi (10 nmol) was blocked by ketanserin,rs 127445 or rs 102221 (0.01 nmol). 5-ht2a/2b/2c receptors were expressed in drg of naïve rats. formalin injection (1%) increased bilaterally 5-ht2a/2b receptors expression in drg. in contrast,formalin injection decreased 5-ht2c receptors expression bilaterally in drg. conclusion data suggest that spinal 5-ht2a/2b/2c receptors have pronociceptive effects and participate in the development and maintenance of formalin-induced long-lasting hypersensitivity. these receptors are expressed in drg and their expression is modulated by formalin. © 2015 institute of pharmacology,polish academy of sciences. published by elsevier sp. z o.o. all rights reserved.