Tags

Type your tag names separated by a space and hit enter

Chronic pain and microglia: the role of ATP.
Novartis Found Symp. 2004; 261:55-64; discussion 64-7, 149-54.NF

Abstract

Pain following nerve damage is an expression of pathological operation of the nervous system, one hallmark of which is tactile allodynia. We have been studying the role of ATP receptors in pain, and have already reported that activation of the P2X2/3 heteromeric channel/receptor in primary sensory neurons causes acutely tactile allodynia. We report here that tactile allodynia under chronic pain states requires an activation of the P2X4 ionotropic ATP receptor and p38 mitogen-activated protein kinase (MAPK) in spinal cord microglia. Two weeks after L5 spinal nerve injury, rats displayed a marked mechanical allodynia. In the rats, activated microglia were detected in the injury side of the dorsal horn where the level of the dually phosphorylated active form of p38MAPK (phospho-p38MAPK) was increased. We performed the double-immunostaining analysis using cell-type specific markers and found that phospho-p38MAPK-positive cells were microglia. Moreover, intraspinal administration of p38MAPK inhibitor, SB203580, suppressed the allodynia. We also found that the expression level of P2X4 was increased strikingly in spinal cord microgila after nerve injury and that pharmacological blockade of P2X4 reversed the allodynia. Intraspinal administration of P2X4 antisense oligodeoxynucleotide (ODN) reduced induction of P2X4 and suppressed tactile allodynia. Taken together our results demonstrate that activation of P2X4 or p38 MAPK in spinal cord microglia is necessary for tactile allodynia following nerve injury.

Authors+Show Affiliations

Division of Biosignaling, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15469044

Citation

Inoue, Kazuhide, et al. "Chronic Pain and Microglia: the Role of ATP." Novartis Foundation Symposium, vol. 261, 2004, pp. 55-64; discussion 64-7, 149-54.
Inoue K, Tsuda M, Koizumi S. Chronic pain and microglia: the role of ATP. Novartis Found Symp. 2004;261:55-64; discussion 64-7, 149-54.
Inoue, K., Tsuda, M., & Koizumi, S. (2004). Chronic pain and microglia: the role of ATP. Novartis Foundation Symposium, 261, 55-64; discussion 64-7, 149-54.
Inoue K, Tsuda M, Koizumi S. Chronic Pain and Microglia: the Role of ATP. Novartis Found Symp. 2004;261:55-64; discussion 64-7, 149-54. PubMed PMID: 15469044.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chronic pain and microglia: the role of ATP. AU - Inoue,Kazuhide, AU - Tsuda,Makoto, AU - Koizumi,Schuichi, PY - 2004/10/8/pubmed PY - 2004/11/13/medline PY - 2004/10/8/entrez SP - 55-64; discussion 64-7, 149-54 JF - Novartis Foundation symposium JO - Novartis Found Symp VL - 261 N2 - Pain following nerve damage is an expression of pathological operation of the nervous system, one hallmark of which is tactile allodynia. We have been studying the role of ATP receptors in pain, and have already reported that activation of the P2X2/3 heteromeric channel/receptor in primary sensory neurons causes acutely tactile allodynia. We report here that tactile allodynia under chronic pain states requires an activation of the P2X4 ionotropic ATP receptor and p38 mitogen-activated protein kinase (MAPK) in spinal cord microglia. Two weeks after L5 spinal nerve injury, rats displayed a marked mechanical allodynia. In the rats, activated microglia were detected in the injury side of the dorsal horn where the level of the dually phosphorylated active form of p38MAPK (phospho-p38MAPK) was increased. We performed the double-immunostaining analysis using cell-type specific markers and found that phospho-p38MAPK-positive cells were microglia. Moreover, intraspinal administration of p38MAPK inhibitor, SB203580, suppressed the allodynia. We also found that the expression level of P2X4 was increased strikingly in spinal cord microgila after nerve injury and that pharmacological blockade of P2X4 reversed the allodynia. Intraspinal administration of P2X4 antisense oligodeoxynucleotide (ODN) reduced induction of P2X4 and suppressed tactile allodynia. Taken together our results demonstrate that activation of P2X4 or p38 MAPK in spinal cord microglia is necessary for tactile allodynia following nerve injury. SN - 1528-2511 UR - https://www.unboundmedicine.com/medline/citation/15469044/Chronic_pain_and_microglia:_the_role_of_ATP_ DB - PRIME DP - Unbound Medicine ER -