title: Oral administration of the p38α MAPK inhibitor, UR13870, inhibits affective pain behavior after spinal cord injury.
abstract: The p38α mitogenous activated protein kinase (MAPK) cell signaling pathway is a key mechanism of microglia activation and has been studied as a target for neuropathic pain. The effect of UR13870, a p38α MAPK inhibitor, on microglia expression in the anterior cingulate cortex (ACC) and spinal dorsal horn was addressed after T9 contusion spinal cord injury (SCI) in the rat, in addition to behavioral testing of pain-related aversion and anxiety. Administration of intravenous UR13870 (1mg/kg i.v.) and pregabalin (30 mg/kg i.v.) reduced place escape avoidance paradigm (PEAP) but did not affect open-field anxiety behavior 42 days after SCI. PEAP behavior was also reduced in animals administered daily with oral UR13870 (10mg/kg p.o.) and preserved spinal tissue 28 days after SCI. Although UR13870 (10mg/kg p.o.) failed to reduce OX-42 and glial fibrillar acid protein immunoreactivity within the spinal dorsal horn, a reduction toward the control level was observed close to the SCI site. In the anterior cingulate cortex (ACC), a significant increase in OX-42 immunoreactivity was identified after SCI. UR13870 (10mg/kg p.o.) treatment significantly reduced OX-42, metabotropic glutamate type 5 receptor (mGluR5), and NMDA (N-methyl-d-aspartate) 2B subunit receptor (NR2B) expression in the ACC after SCI. To conclude, oral treatment with a p38α MAPK inhibitor reduces the affective behavioral component of pain after SCI in association with a reduction of microglia and specific glutamate receptors within the ACC. Nevertheless the role of neuroinflammatory processes within the vicinity of the SCI site in the development of affective neuropathic pain cannot be excluded.
authors.affiliation: Sensorimotor Function Group, Hospital Nacional de Parapléjicos, SESCAM, Toledo, Spain.
authors.forename: Iriana
authors.initials: I
authors.lastname: Galan-Arriero
authors.affiliation: Sensorimotor Function Group, Hospital Nacional de Parapléjicos, SESCAM, Toledo, Spain.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Avila-Martin
authors.affiliation: Sensorimotor Function Group, Hospital Nacional de Parapléjicos, SESCAM, Toledo, Spain.
authors.forename: Agueda
authors.initials: A
authors.lastname: Ferrer-Donato
authors.affiliation: Sensorimotor Function Group, Hospital Nacional de Parapléjicos, SESCAM, Toledo, Spain; E.U.E. Fisioterapia de Toledo, Universidad de Castilla la Mancha, Toledo, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Gomez-Soriano
authors.affiliation: Sensorimotor Function Group, Hospital Nacional de Parapléjicos, SESCAM, Toledo, Spain; IAI, Consejo Superior de Investigaciones Científicas (CSIC), Arganda del Rey, Spain.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bravo-Esteban
authors.affiliation: Sensorimotor Function Group, Hospital Nacional de Parapléjicos, SESCAM, Toledo, Spain. Electronic address: jscott@sescam.org.
authors.forename: Julian
authors.initials: J
authors.lastname: Taylor
mesh_terms: D000818:Animals; D001007:Anxiety / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009437:Neuralgia / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000150:complications* / Q000503:physiopathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; C530087:Org 48762-0; D011725:Pyridines; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Affective cognitive pain component; Anterior cingulate cortex; Anxiety; Microglia; Neuropathic pain; P38α MAPK; Place escape avoidance paradigm; Spinal cord injury