title: Formalin injection produces long-lasting hypersensitivity with characteristics of neuropathic pain.
abstract: The purpose of this study was to investigate whether 1%, 2% or 5% formalin injection produce hypersensitivity with characteristics of the neuropathic pain induced by spinal nerve injury. Formalin injection (1%, 2% and 5%) produced concentration-dependent long-lasting (at least 14 days) mechanical allodynia and hyperalgesia in both paws. Likewise, L5/L6 spinal nerve ligation induced allodynia and hyperalgesia in both paws. The intensity of hypersensitivity was greater in the ipsilateral than in the contralateral paw in all models. Systemic gabapentin or morphine completely reduced 1% formalin-induced hypersensitivity. In contrast, both drugs were not able to fully diminish 2-5% formalin- and nerve injury-induced hypersensitivity. Indomethacin produced a significant effect in the chronic 1% formalin test. Conversely, this drug did not modify 2 or 5% formalin- and nerve injury-induced hypersensitivity. Spinal nerve injury and 2-5%, but not 1%, formalin injection enhanced ATF3 protein expression and immunofluorescence in dorsal root ganglia (DRG) in a time-dependent manner. Furthermore, 2-5%, but not 1%, formalin injection or spinal nerve injury also enhanced α2δ-1 subunit protein levels in DRG. Our results suggest that 5% and, at lesser extent, 2% formalin injection produces long-lasting hypersensitivity with a pharmacological and molecular pattern that resembles neuropathic pain induced by spinal nerve ligation.
authors.affiliation: Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur, Ciudad de México, Mexico.
authors.forename: Ana Belen
authors.initials: AB
authors.lastname: Salinas-Abarca
authors.affiliation: Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur, Ciudad de México, Mexico.
authors.forename: Sabino Hazael
authors.initials: SH
authors.lastname: Avila-Rojas
authors.affiliation: Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur, Ciudad de México, Mexico.
authors.forename: Paulino
authors.initials: P
authors.lastname: Barragán-Iglesias
authors.affiliation: Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur, Ciudad de México, Mexico.
authors.forename: Jorge Baruch
authors.initials: JB
authors.lastname: Pineda-Farias
authors.affiliation: Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur, Ciudad de México, Mexico. Electronic address: vgranados@cinvestav.mx.
authors.forename: Vinicio
authors.initials: V
authors.lastname: Granados-Soto
mesh_terms: D051700:Activating Transcription Factor 3 / Q000378:metabolism; D000588:Amines / Q000494:pharmacology; D000818:Animals; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D005260:Female; D005557:Formaldehyde / Q000008:administration & dosage / Q000494:pharmacology*; D000077206:Gabapentin; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D007267:Injections; D008026:Ligation / Q000009:adverse effects; D009020:Morphine / Q000494:pharmacology; D009437:Neuralgia / Q000139:chemically induced* / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D051700:Activating Transcription Factor 3; D000588:Amines; C497108:Atf3 protein, rat; D003509:Cyclohexanecarboxylic Acids; D005557:Formaldehyde; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D009020:Morphine; D007213:Indomethacin
keywords: ATF3; Chronic pain; Formalin test; Neuropathic pain; α(2)δ−1 subunit