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

• Published in: Pharmacological reports 2016-04, Vol.68 (2), p.434-442
• Main Authors: Cervantes-Durán, Claudia, Vidal-Cantú, Guadalupe C., Godínez-Chaparro, Beatriz, Granados-Soto, Vinicio
• Format: Article
• Language: English
• Subjects: 5-HT2 receptors; Allodynia; Animals; Drug Safety and Pharmacovigilance; Female; Formaldehyde - pharmacology; Ganglia, Spinal - drug effects; Ganglia, Spinal - metabolism; Hyperalgesia; Hyperalgesia - chemically induced; Hyperalgesia - metabolism; Ketanserin - pharmacology; Long-lasting pain; Original Research Article; Pain Measurement - methods; Pharmacotherapy; Pharmacy; Pyrimidines - pharmacology; Rats; Rats, Wistar; Receptors, Serotonin, 5-HT2 - metabolism; Spinal Cord - drug effects; Spinal Cord - metabolism; Spiro Compounds - pharmacology; Sulfonamides - pharmacology
• ISSN: 1734-1140; 2299-5684
• DOI: 10.1016/j.pharep.2015.11.009

•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. 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. 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. 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 (1–10nmol), increased 0.5% formalin-induced secondary allodynia and hyperalgesia in both paws. In contrast, intrathecal pre-treatment with the selective 5-HT2A (ketanserin 1–100nmol), 5-HT2B (RS 127445 1–100nmol) or 5-HT2C (RS 102221 1–100nmol) receptor antagonists prevented and reversed, respectively, 1% formalin-induced secondary allodynia and hyperalgesia in both paws. Likewise, the pronociceptive effect of DOI (10nmol) was blocked by ketanserin, RS 127445 or RS 102221 (0.01nmol). 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. 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.