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Nitric oxide synthase modulates CFA-induced thermal hyperalgesia through cytokine regulation in mice.
Mol Pain. 2010 Mar 02; 6:13.MP

Abstract

BACKGROUND

Although it has been largely demonstrated that nitric oxide synthase (NOS), a key enzyme for nitric oxide (NO) production, modulates inflammatory pain, the molecular mechanisms underlying these effects remain to be clarified. Here we asked whether cytokines, which have well-described roles in inflammatory pain, are downstream targets of NO in inflammatory pain and which of the isoforms of NOS are involved in this process.

RESULTS

Intraperitoneal (i.p.) pretreatment with 7-nitroindazole sodium salt (7-NINA, a selective neuronal NOS inhibitor), aminoguanidine hydrochloride (AG, a selective inducible NOS inhibitor), L-N(G)-nitroarginine methyl ester (L-NAME, a non-selective NOS inhibitor), but not L-N(5)-(1-iminoethyl)-ornithine (L-NIO, a selective endothelial NOS inhibitor), significantly attenuated thermal hyperalgesia induced by intraplantar (i.pl.) injection of complete Freund's adjuvant (CFA). Real-time reverse transcription-polymerase chain reaction (RT-PCR) revealed a significant increase of nNOS, iNOS, and eNOS gene expression, as well as tumor necrosis factor-alpha (TNF), interleukin-1 beta (IL-1beta), and interleukin-10 (IL-10) gene expression in plantar skin, following CFA. Pretreatment with the NOS inhibitors prevented the CFA-induced increase of the pro-inflammatory cytokines TNF and IL-1beta. The increase of the anti-inflammatory cytokine IL-10 was augmented in mice pretreated with 7-NINA or L-NAME, but reduced in mice receiving AG or L-NIO. NNOS-, iNOS- or eNOS-knockout (KO) mice had lower gene expression of TNF, IL-1beta, and IL-10 following CFA, overall corroborating the inhibitor data.

CONCLUSION

These findings lead us to propose that inhibition of NOS modulates inflammatory thermal hyperalgesia by regulating cytokine expression.

Authors+Show Affiliations

Department of Neurology, University of Würzburg, Josef-Schneider-Str 11, 97080 Würzburg, Germany. Chen_Y@klinik.uni-wuerzburg.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

20193086

Citation

Chen, Yong, et al. "Nitric Oxide Synthase Modulates CFA-induced Thermal Hyperalgesia Through Cytokine Regulation in Mice." Molecular Pain, vol. 6, 2010, p. 13.
Chen Y, Boettger MK, Reif A, et al. Nitric oxide synthase modulates CFA-induced thermal hyperalgesia through cytokine regulation in mice. Mol Pain. 2010;6:13.
Chen, Y., Boettger, M. K., Reif, A., Schmitt, A., Uçeyler, N., & Sommer, C. (2010). Nitric oxide synthase modulates CFA-induced thermal hyperalgesia through cytokine regulation in mice. Molecular Pain, 6, 13. https://doi.org/10.1186/1744-8069-6-13
Chen Y, et al. Nitric Oxide Synthase Modulates CFA-induced Thermal Hyperalgesia Through Cytokine Regulation in Mice. Mol Pain. 2010 Mar 2;6:13. PubMed PMID: 20193086.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nitric oxide synthase modulates CFA-induced thermal hyperalgesia through cytokine regulation in mice. AU - Chen,Yong, AU - Boettger,Michael K, AU - Reif,Andreas, AU - Schmitt,Angelika, AU - Uçeyler,Nurcan, AU - Sommer,Claudia, Y1 - 2010/03/02/ PY - 2009/11/23/received PY - 2010/03/02/accepted PY - 2010/3/3/entrez PY - 2010/3/3/pubmed PY - 2010/6/11/medline SP - 13 EP - 13 JF - Molecular pain JO - Mol Pain VL - 6 N2 - BACKGROUND: Although it has been largely demonstrated that nitric oxide synthase (NOS), a key enzyme for nitric oxide (NO) production, modulates inflammatory pain, the molecular mechanisms underlying these effects remain to be clarified. Here we asked whether cytokines, which have well-described roles in inflammatory pain, are downstream targets of NO in inflammatory pain and which of the isoforms of NOS are involved in this process. RESULTS: Intraperitoneal (i.p.) pretreatment with 7-nitroindazole sodium salt (7-NINA, a selective neuronal NOS inhibitor), aminoguanidine hydrochloride (AG, a selective inducible NOS inhibitor), L-N(G)-nitroarginine methyl ester (L-NAME, a non-selective NOS inhibitor), but not L-N(5)-(1-iminoethyl)-ornithine (L-NIO, a selective endothelial NOS inhibitor), significantly attenuated thermal hyperalgesia induced by intraplantar (i.pl.) injection of complete Freund's adjuvant (CFA). Real-time reverse transcription-polymerase chain reaction (RT-PCR) revealed a significant increase of nNOS, iNOS, and eNOS gene expression, as well as tumor necrosis factor-alpha (TNF), interleukin-1 beta (IL-1beta), and interleukin-10 (IL-10) gene expression in plantar skin, following CFA. Pretreatment with the NOS inhibitors prevented the CFA-induced increase of the pro-inflammatory cytokines TNF and IL-1beta. The increase of the anti-inflammatory cytokine IL-10 was augmented in mice pretreated with 7-NINA or L-NAME, but reduced in mice receiving AG or L-NIO. NNOS-, iNOS- or eNOS-knockout (KO) mice had lower gene expression of TNF, IL-1beta, and IL-10 following CFA, overall corroborating the inhibitor data. CONCLUSION: These findings lead us to propose that inhibition of NOS modulates inflammatory thermal hyperalgesia by regulating cytokine expression. SN - 1744-8069 UR - https://www.unboundmedicine.com/medline/citation/20193086/Nitric_oxide_synthase_modulates_CFA_induced_thermal_hyperalgesia_through_cytokine_regulation_in_mice_ L2 - https://journals.sagepub.com/doi/10.1186/1744-8069-6-13?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -