title: Formalin-induced long-term secondary allodynia and hyperalgesia are maintained by descending facilitation.
abstract: This work analyzes the role of cholecystokinin (CCK) receptors, dynorphin A₁₋₁₇ and descending facilitation originated in the rostral ventromedial medulla (RVM) on secondary allodynia and hyperalgesia in formalin-injected rats. Formalin injection (50 μL, 1%, s.c.) produced acute nociception (lasting 1 h) and long-term secondary allodynia and hyperalgesia in ipsilateral and contralateral hind paws (lasting 1-12 days). Once established, intra-RVM administration of lidocaine at day 6, but not at 2, reversed secondary allodynia and hyperalgesia in rats. The injection of YM022 (CCK₂ receptor antagonist), but not lorglumide (CCK₁ receptor antagonist), into the RVM or spinal cord reversed both nociceptive behaviors. Pre-treatment with lidocaine, lorglumide or YM022 did not prevent the development of secondary allodynia or hyperalgesia regardless of the administration route. Formalin injection increased dynorphin content in the dorsal, but not the ventral, spinal cord sections at day 6. Moreover, intrathecal administration of dynorphin antiserum reversed, but was unable to prevent, secondary allodynia and hyperalgesia in both hind paws. These results suggest that formalin-induced secondary allodynia and hyperalgesia are maintained by activation of descending facilitatory mechanisms which are dependent on CCK₂ receptors located in the RVM and spinal cord. In addition, data suggest that spinal dynorphin A₁₋₁₇ and CCK play an important role in formalin-induced secondary allodynia and hyperalgesia.
authors.affiliation: Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados, Sede Sur, México, D.F., Mexico.
authors.forename: Mónica
authors.initials: M
authors.lastname: Ambriz-Tututi
authors.forename: Silvia L
authors.initials: SL
authors.lastname: Cruz
authors.forename: Héctor
authors.initials: H
authors.lastname: Urquiza-Marín
authors.forename: Vinicio
authors.initials: V
authors.lastname: Granados-Soto
mesh_terms: D000818:Animals; D004399:Dynorphins / Q000378:metabolism; D005260:Female; D005557:Formaldehyde / Q000494:pharmacology*; D006930:Hyperalgesia / Q000139:chemically induced*; D007106:Immune Sera; D008526:Medulla Oblongata / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D011949:Receptors, Cholecystokinin / Q000502:physiology*; D013116:Spinal Cord / Q000378:metabolism
chemical_list: D007106:Immune Sera; D011949:Receptors, Cholecystokinin; D005557:Formaldehyde; D004399:Dynorphins