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

• Formalin injection produced secondary allodynia and hyperalgesia.
• Intrathecal DOI increased formalin-induced hypersensitivity.
• The pronociceptive effect of DOI was blocked by ketanserin, RS 127445 or RS 102221.
• Ketanserin, RS 127445 or RS 102221 reduced formalin-induced hypersensitivity.
• Formalin increased 5-HT2A and 5-HT2B receptors expression in DRG.

BackgroundThe 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.Methods0.5–1% 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.ResultsFormalin (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.ConclusionData 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.