title: Role of spinal 5-HT2 receptors subtypes in formalin-induced long-lasting hypersensitivity.
abstract: 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 (1-10nmol), 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: División de Estudios de Posgrado de la Facultad de Ciencias Médicas y Biológicas "Dr. Ignacio Chávez", Morelia Michoacán, Mexico.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cervantes-Durán
authors.affiliation: Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur, México, D.F., Mexico.
authors.forename: Guadalupe C
authors.initials: GC
authors.lastname: Vidal-Cantú
authors.affiliation: Departamento de Sistemas Biológicos, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana-Xochimilco, México, D.F., Mexico.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Godínez-Chaparro
authors.affiliation: Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur, México, D.F., Mexico. Electronic address: vgranados@prodigy.net.mx.
authors.forename: Vinicio
authors.initials: V
authors.lastname: Granados-Soto
mesh_terms: D000818:Animals; D005260:Female; D005557:Formaldehyde / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D006930:Hyperalgesia / Q000139:chemically induced* / Q000378:metabolism*; D007650:Ketanserin / Q000494:pharmacology; D010147:Pain Measurement / Q000379:methods; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044348:Receptors, Serotonin, 5-HT2 / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013141:Spiro Compounds / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: C107821:8-(5-(5-amino-2,4-dimethoxyphenyl)-5-oxopentyl)-1,3,8-triazaspiro(4.5)decane-2,4-dione; D011743:Pyrimidines; D044348:Receptors, Serotonin, 5-HT2; D013141:Spiro Compounds; D013449:Sulfonamides; C121466:2-amino-4-(4-fluoronaphth-1-yl)-6-isopropylpyrimidine; D005557:Formaldehyde; D007650:Ketanserin
keywords: 5-HT(2) receptors; Allodynia; Hyperalgesia; Long-lasting pain