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Activation of p38 mitogen-activated protein kinase in spinal hyperactive microglia contributes to pain hypersensitivity following peripheral nerve injury.
Glia. 2004 Jan 01; 45(1):89-95.GLIA

Abstract

Neuropathic pain is an expression of pathological operation of the nervous system, which commonly results from nerve injury and is characterized by pain hypersensitivity to innocuous stimuli, a phenomenon known as tactile allodynia. The mechanisms by which nerve injury creates tactile allodynia have remained largely unknown. We report that the development of tactile allodynia following nerve injury requires activation of p38 mitogen-activated protein kinase (p38MAPK), a member of the MAPK family, in spinal microglia. We found that immunofluorescence and protein levels of the dually phosphorylated active form of p38MAPK (phospho-p38MAPK) were increased in the dorsal horn ipsilateral to spinal nerve injury. Interestingly, the phospho-p38MAPK immunofluorescence in the dorsal horn was found exclusively in microglia, but not in neurons or astrocytes. The level of phospho-p38MAPK immunofluorescence in individual microglial cells was much higher in the hyperactive phenotype in the ipsilateral dorsal horn than the resting one in the contralateral side. Intrathecal administration of the p38MAPK inhibitor, 4-(4-fluorophenyl)-2-(4-methylsulfonylphenyl)-5-(4-pyridyl)-1H-imidazole (SB203580), suppresses development of the nerve injury-induced tactile allodynia. Taken together, our results demonstrate that nerve injury-induced pain hypersensitivity depends on activation of the p38MAPK signaling pathway in hyperactive microglia in the dorsal horn following peripheral nerve injury.

Authors+Show Affiliations

Division of Biosignaling, National Institute of Health Sciences, Tokyo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14648549

Citation

Tsuda, Makoto, et al. "Activation of P38 Mitogen-activated Protein Kinase in Spinal Hyperactive Microglia Contributes to Pain Hypersensitivity Following Peripheral Nerve Injury." Glia, vol. 45, no. 1, 2004, pp. 89-95.
Tsuda M, Mizokoshi A, Shigemoto-Mogami Y, et al. Activation of p38 mitogen-activated protein kinase in spinal hyperactive microglia contributes to pain hypersensitivity following peripheral nerve injury. Glia. 2004;45(1):89-95.
Tsuda, M., Mizokoshi, A., Shigemoto-Mogami, Y., Koizumi, S., & Inoue, K. (2004). Activation of p38 mitogen-activated protein kinase in spinal hyperactive microglia contributes to pain hypersensitivity following peripheral nerve injury. Glia, 45(1), 89-95.
Tsuda M, et al. Activation of P38 Mitogen-activated Protein Kinase in Spinal Hyperactive Microglia Contributes to Pain Hypersensitivity Following Peripheral Nerve Injury. Glia. 2004 Jan 1;45(1):89-95. PubMed PMID: 14648549.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of p38 mitogen-activated protein kinase in spinal hyperactive microglia contributes to pain hypersensitivity following peripheral nerve injury. AU - Tsuda,Makoto, AU - Mizokoshi,Akito, AU - Shigemoto-Mogami,Yukari, AU - Koizumi,Schuichi, AU - Inoue,Kazuhide, PY - 2003/12/4/pubmed PY - 2004/2/11/medline PY - 2003/12/4/entrez SP - 89 EP - 95 JF - Glia JO - Glia VL - 45 IS - 1 N2 - Neuropathic pain is an expression of pathological operation of the nervous system, which commonly results from nerve injury and is characterized by pain hypersensitivity to innocuous stimuli, a phenomenon known as tactile allodynia. The mechanisms by which nerve injury creates tactile allodynia have remained largely unknown. We report that the development of tactile allodynia following nerve injury requires activation of p38 mitogen-activated protein kinase (p38MAPK), a member of the MAPK family, in spinal microglia. We found that immunofluorescence and protein levels of the dually phosphorylated active form of p38MAPK (phospho-p38MAPK) were increased in the dorsal horn ipsilateral to spinal nerve injury. Interestingly, the phospho-p38MAPK immunofluorescence in the dorsal horn was found exclusively in microglia, but not in neurons or astrocytes. The level of phospho-p38MAPK immunofluorescence in individual microglial cells was much higher in the hyperactive phenotype in the ipsilateral dorsal horn than the resting one in the contralateral side. Intrathecal administration of the p38MAPK inhibitor, 4-(4-fluorophenyl)-2-(4-methylsulfonylphenyl)-5-(4-pyridyl)-1H-imidazole (SB203580), suppresses development of the nerve injury-induced tactile allodynia. Taken together, our results demonstrate that nerve injury-induced pain hypersensitivity depends on activation of the p38MAPK signaling pathway in hyperactive microglia in the dorsal horn following peripheral nerve injury. SN - 0894-1491 UR - https://www.unboundmedicine.com/medline/citation/14648549/Activation_of_p38_mitogen_activated_protein_kinase_in_spinal_hyperactive_microglia_contributes_to_pain_hypersensitivity_following_peripheral_nerve_injury_ L2 - https://doi.org/10.1002/glia.10308 DB - PRIME DP - Unbound Medicine ER -