期刊
BIOMEDICAL REPORTS
卷 3, 期 5, 页码 703-706出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/br.2015.497
关键词
inflammatory pain; Janus kinase 2 inhibitor; AG490; thermal hyperalgesia; mechanical hyperalgesia
资金
- United States Army Medical Research and Material Command Combat Causality Care Research program
- Clinical and Rehabilitative Medicine Research program
- National Research Council Senior Research Associate Fellowship
Interleukin 6 (IL-6) has a critical role in pain mechanisms. IL-6 signals through the Janus-activated kinases 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) pathway. The contribution of JAK2 signaling in inflammation-induced hyperalgesia has not been addressed previously. The role of this pathway was investigated using the JAK2 inhibitor, AG490, in a rat model of inflammatory pain. Unilateral hind paw inflammatory pain was induced in male Sprague-Dawley rats by intraplantar (i.pl.) injection of 3.5% lambda-carrageenan. Inflamed rats received an i.pl. injection of either 3.5% of dimethylsulfoxide or AG490 (1-10 mu g). The antinociceptive effects of AG490 were assessed by 2 pain behavioral assays 4 h later: The thermal and mechanical hyperalgesia tests. AG490 (1-10 mu g) significantly attenuated lambda-carrageenan-induced thermal hyperalgesia in a dosedependent manner. AG490 also reduced mechanical hyperalgesia. Co-administration of opioid receptor antagonist naloxone (10 mu g) and AG490 (10 mu g) did not reverse AG490-produced antinociceptive activity, suggesting that the mu-opioid receptor is not responsible for the anti-hyperalgesic effects of AG490. Therefore, we suggest that AG490 produces these effects by blocking JAK2 signaling. In conclusion, JAK2 inhibitors may represent a novel class of non-narcotic drugs to treat inflammatory pain.
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