Anti-hyperalgesic effects of AG490, a Janus kinase inhibitor, in a rat model of inflammatory pain

Cheppudira,Bopaiah  P.; Garza,Thomas  H.; Petz,Lawrence  N.; Clifford,John L.; Fowler,Marcie

doi:10.3892/br.2015.497

Anti-hyperalgesic effects of AG490, a Janus kinase inhibitor, in a rat model of inflammatory pain

Authors:
- Bopaiah P. Cheppudira
- Thomas H. Garza
- Lawrence N. Petz
- John L. Clifford
- Marcie Fowler
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Affiliations: U.S. Army Institute of Surgical Research, Battlefield Pain Management Research Task Area, Fort Sam Houston, TX 78234, USA
Published online on: July 27, 2015 https://doi.org/10.3892/br.2015.497
Pages: 703-706

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Abstract

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% ʎ‑carrageenan. Inflamed rats received an i.pl. injection of either 3.5% of dimethylsulfoxide or AG490 (1‑10 µg). The antinociceptive effects of AG490 were assessed by 2 pain behavioral assays 4 h later: The thermal and mechanical hyperalgesia tests. AG490 (1‑10 µg) significantly attenuated ʎ‑carrageenan‑induced thermal hyperalgesia in a dose‑dependent manner. AG490 also reduced mechanical hyperalgesia. Co‑administration of opioid receptor antagonist naloxone (10 µg) and AG490 (10 µg) did not reverse AG490‑produced antinociceptive activity, suggesting that the µ‑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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