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Inhibition of p38 mitogen-activated protein kinase attenuates interleukin-1beta-induced thermal hyperalgesia and inducible nitric oxide synthase expression in the spinal cord.
J Neurochem 2005; 94(3):742-52JN

Abstract

We have reported recently that intrathecal (i.t.) injection of interleukin-1beta (IL-1beta), at a dose of 100 ng, induces inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production in the spinal cord and results in thermal hyperalgesia in rats. This study further examines the role of mitogen-activated protein kinase (MAPK) in i.t. IL-1beta-mediated iNOS-NO cascade in spinal nociceptive signal transduction. All rats were implanted with an i.t. catheter either with or without an additional microdialysis probe. Paw withdrawal latency to radiant heat is used to assess thermal hyperalgesia. The iNOS and MAPK protein expression in the spinal cord dorsal horn were examined by western blot. The [NO] in CSF dialysates were also measured. Intrathecal IL-1beta leads to a time-dependent up-regulation of phosphorylated p38 (p-p38) MAPK protein expression in the spinal cord 30-240 min following IL-1beta injection (i.t.). However, neither the phosphorylated extracellular signal-regulated kinase (p-ERK) nor phosphorylated c-Jun NH2-terminal kinase (p-JNK) was affected. The total amount of p38, ERK, and JNK MAPK proteins were not affected following IL-1beta injection. Intrathecal administration of either selective p38 MAPK, or JNK, or ERK inhibitor alone did not affect the thermal nociceptive threshold or iNOS protein expression in the spinal cord. However, pretreatment with a p38 MAPK inhibitor significantly reduced the IL-1beta-induced p-p38 MAPK expression by 38-49%, and nearly completely blocked the subsequent iNOS expression (reduction by 86.6%), NO production, and thermal hyperalgesia. In contrast, both ERK and JNK inhibitor pretreatments only partially (approximately 50%) inhibited the IL-1beta-induced iNOS expression in the spinal cord. Our results suggest that p38 MAPK plays a pivotal role in i.t. IL-1beta-induced spinal sensitization and nociceptive signal transduction.

Authors+Show Affiliations

Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

16033422

Citation

Sung, Chun-Sung, et al. "Inhibition of P38 Mitogen-activated Protein Kinase Attenuates Interleukin-1beta-induced Thermal Hyperalgesia and Inducible Nitric Oxide Synthase Expression in the Spinal Cord." Journal of Neurochemistry, vol. 94, no. 3, 2005, pp. 742-52.
Sung CS, Wen ZH, Chang WK, et al. Inhibition of p38 mitogen-activated protein kinase attenuates interleukin-1beta-induced thermal hyperalgesia and inducible nitric oxide synthase expression in the spinal cord. J Neurochem. 2005;94(3):742-52.
Sung, C. S., Wen, Z. H., Chang, W. K., Chan, K. H., Ho, S. T., Tsai, S. K., ... Wong, C. S. (2005). Inhibition of p38 mitogen-activated protein kinase attenuates interleukin-1beta-induced thermal hyperalgesia and inducible nitric oxide synthase expression in the spinal cord. Journal of Neurochemistry, 94(3), pp. 742-52.
Sung CS, et al. Inhibition of P38 Mitogen-activated Protein Kinase Attenuates Interleukin-1beta-induced Thermal Hyperalgesia and Inducible Nitric Oxide Synthase Expression in the Spinal Cord. J Neurochem. 2005;94(3):742-52. PubMed PMID: 16033422.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of p38 mitogen-activated protein kinase attenuates interleukin-1beta-induced thermal hyperalgesia and inducible nitric oxide synthase expression in the spinal cord. AU - Sung,Chun-Sung, AU - Wen,Zhi-Hong, AU - Chang,Wen-Kuei, AU - Chan,Kwok-Hon, AU - Ho,Shung-Tai, AU - Tsai,Shen-Kou, AU - Chang,Yi-Chen, AU - Wong,Chih-Shung, PY - 2005/7/22/pubmed PY - 2005/9/20/medline PY - 2005/7/22/entrez SP - 742 EP - 52 JF - Journal of neurochemistry JO - J. Neurochem. VL - 94 IS - 3 N2 - We have reported recently that intrathecal (i.t.) injection of interleukin-1beta (IL-1beta), at a dose of 100 ng, induces inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production in the spinal cord and results in thermal hyperalgesia in rats. This study further examines the role of mitogen-activated protein kinase (MAPK) in i.t. IL-1beta-mediated iNOS-NO cascade in spinal nociceptive signal transduction. All rats were implanted with an i.t. catheter either with or without an additional microdialysis probe. Paw withdrawal latency to radiant heat is used to assess thermal hyperalgesia. The iNOS and MAPK protein expression in the spinal cord dorsal horn were examined by western blot. The [NO] in CSF dialysates were also measured. Intrathecal IL-1beta leads to a time-dependent up-regulation of phosphorylated p38 (p-p38) MAPK protein expression in the spinal cord 30-240 min following IL-1beta injection (i.t.). However, neither the phosphorylated extracellular signal-regulated kinase (p-ERK) nor phosphorylated c-Jun NH2-terminal kinase (p-JNK) was affected. The total amount of p38, ERK, and JNK MAPK proteins were not affected following IL-1beta injection. Intrathecal administration of either selective p38 MAPK, or JNK, or ERK inhibitor alone did not affect the thermal nociceptive threshold or iNOS protein expression in the spinal cord. However, pretreatment with a p38 MAPK inhibitor significantly reduced the IL-1beta-induced p-p38 MAPK expression by 38-49%, and nearly completely blocked the subsequent iNOS expression (reduction by 86.6%), NO production, and thermal hyperalgesia. In contrast, both ERK and JNK inhibitor pretreatments only partially (approximately 50%) inhibited the IL-1beta-induced iNOS expression in the spinal cord. Our results suggest that p38 MAPK plays a pivotal role in i.t. IL-1beta-induced spinal sensitization and nociceptive signal transduction. SN - 0022-3042 UR - https://www.unboundmedicine.com/medline/citation/16033422/Inhibition_of_p38_mitogen_activated_protein_kinase_attenuates_interleukin_1beta_induced_thermal_hyperalgesia_and_inducible_nitric_oxide_synthase_expression_in_the_spinal_cord_ L2 - https://doi.org/10.1111/j.1471-4159.2005.03226.x DB - PRIME DP - Unbound Medicine ER -