title: Participation of the central p38 and ERK1/2 pathways in IL-1β-induced sensitization of nociception in rats.
abstract: This study examined the participation of central mitogen-activated protein kinases (MAPKs) in the central sensitization produced by a subcutaneous injection of interleukin-1β (IL-1β) in male Sprague-Dawley rats. Formalin-induced responses were evaluated 24h after an IL-1β injection. A subcutaneous injection of 10ng of IL-1β elevated the formalin-induced scratching response significantly in the second phase compared to the vehicle-treated group. Pretreatment with an IL-1 receptor antagonist reduced the IL-1β-induced sensitization. Pretreatment with IL-1β increased the p-ERK and p-p38 expression induced by the formalin injection. Double immunofluorescence data revealed increases in phospho-extracellular signal-regulated kinase (p-ERK) immunoreactive cells that co-localize with neuronal nuclei (NeuN), a neuronal marker, and in phospho-p38 (p-p38) immunoreactive cells that co-localize with NeuN and OX42, a microglia marker. The intracisternal administration of minocycline (50μg), a microglia inhibitor, attenuated the increased formalin-induced scratching responses in the IL-1β-treated rats. The intracisternal administration of PD98059 (1, 10μg), a MEK inhibitor, and SB203580 (1, 5μg), a p38 inhibitor, also attenuated the number of formalin-induced scratches in the second phase in the IL-1β-treated rats. These results suggest that the IL-1β-induced central sensitization of nociception is mediated by the central MAPK pathways, which are activated differentially in the neurons and microglia under inflammatory pain conditions. Therefore, blockade of the MAPK pathways can be as a potential therapeutic target for the central sensitization of inflammatory pain.
authors.affiliation: Department of Oral Physiology, School of Dentistry, Kyungpook National University, Daegu 700-412, Republic of Korea.
authors.forename: Kui Y
authors.initials: KY
authors.lastname: Yang
authors.forename: Won S
authors.initials: WS
authors.lastname: Bae
authors.forename: Min J
authors.initials: MJ
authors.lastname: Kim
authors.forename: Yong C
authors.initials: YC
authors.lastname: Bae
authors.forename: Young J
authors.initials: YJ
authors.lastname: Kim
authors.forename: Hyun J
authors.initials: HJ
authors.lastname: Kim
authors.forename: Soon H
authors.initials: SH
authors.lastname: Nam
authors.forename: Dong K
authors.initials: DK
authors.lastname: Ahn
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005157:Facial Pain / Q000139:chemically induced* / Q000201:enzymology*; D053583:Interleukin-1beta / Q000633:toxicity*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008297:Male; D059225:Nociception / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis*
chemical_list: D053583:Interleukin-1beta; D010446:Peptide Fragments; C052994:interleukin-1beta (163-171); D048051:p38 Mitogen-Activated Protein Kinases
keywords: ERK; GFAP; Hyperalgesia; IL-1β; MAPK; Microglia; NeuN; Sensitization; extracellular signal-regulated kinase; glial fibrillary acidic protein; interleukin-1β; mitogen-activated protein kinase; neuronal nuclei