title: Activation of different signals identified with glia cells contribute to the progression of hyperalgesia.
abstract: Hyperalgesia results from a decreased pain threshold, often subsequent to peripheral tissue damage. Recent reports revealed several promising mechanisms of hyperalgesia, but many issues remain unclear. The glial activation accompanying inflammation of neurotransmission in the spinal cord might be related to the initiation and maintenance of hyperalgesia. The present study investigated the pharmacological pain-modifying effects of mitogen-associated protein kinase (MAPK)-related inhibitors identified with glia cells over time during inflammatory pain. A model of inflammatory pain was produced by injecting mustard oil (MO) into the hind paws of rats. Following MO injection, the changes in paws flinching as the early onset of pain and paw withdrawal latency (PWL) in response to thermal stimulation were measured as delayed-onset hyperalgesia. Before and after the MO injection, one of the inhibitors, a p38-MAPK (SB), nuclear factor (NF)-κB (PDTC), BDNF-trk-B (K252a), or JNK-1 (SP), was administered and flinching and PWL were measured. In the SB, PDTC, and k252a groups, early flinching following MO injection was moderately suppressed. Hyperalgesia was significantly suppressed in the left-right difference of PWL in animals receiving SB, k252a, or PDTC pre-treatment. In animals receiving post-treatment, the suppressive effects were most potent in the SP group. The present results revealed that microglial activation resulting from the release of the phosphatase p38-MAPK, the transcription factor NF-κB, and BDNF contributes to the early stage of inflammatory pain. Astrocyte activation accompanying JNK activation contributes to subsequent hyperalgesia. Activation of different signals identified with glia cells is thought to contribute to the progression of hyperalgesia, which represents an applicable finding for the treatment of hyperalgesia.
authors.affiliation: Division of Neurosciences, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kishishita
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yoshida
authors.forename: Daisuke
authors.initials: D
authors.lastname: Miura
authors.forename: Hidenori
authors.initials: H
authors.lastname: Suzuki
authors.forename: Kozo
authors.initials: K
authors.lastname: Ishikawa
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Miyazaki
authors.forename: Junzo
authors.initials: J
authors.lastname: Nojima
authors.forename: Misa
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Toshizo
authors.initials: T
authors.lastname: Ishikawa
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology; D018450:Disease Progression; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006930:Hyperalgesia / Q000378:metabolism* / Q000473:pathology*; D007267:Injections; D008297:Male; D009149:Mustard Plant; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology*; D010812:Physical Stimulation; D010938:Plant Oils / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D015398:Signal Transduction; D013116:Spinal Cord / Q000473:pathology; D013194:Staining and Labeling
chemical_list: D005904:Glial Fibrillary Acidic Protein; D010938:Plant Oils; C027793:mustard oil