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Accession Number:
AD1191139
Title:
Optimizing Kv7 Channel Openers for Treatment of GWI Pain
Report Date:
2022-07-01
Abstract:
Our laboratory developed a rat model of the chronic pain of GWI. After identification of several molecular maladaptations in pain sensing neurons (nociceptors) after exposure to GW neurotoxicants, we initiated studies to identify effective treatments to reverse established pain-signs. Kv7 openers (KVOs) have known analgesic/palliative capacities that could serve as treatments for the chronic pain associated with GWI. We previously reported that the classic KVO, Retigabine (RET), could temporarily reverse signs of GWI pain in rats. This project examined whether NSAID KVOs (Diclofenac (DIC) and Meclofenamate (MEC)), could act synergistically with RET to improve analgesic potency. We determined that combinations of RET/DIC, RET/MEC and MEC/DIC synergized to improve both molecular and cellular events in nociceptors. In our animal model of GWI chronic pain, RET/MEC reversed pain-signs in rats 14 weeks after exposure to GW neurotoxicants without the side effects observed with RET/DIC. Chronic treatment with RET/MEC should be examined to determine whether side effects would emerge.
Document Type:
Conference:
Journal:
Pages:
204
File Size:
8.14MB
W81XWH-19-1-0657
(W81XWH1910657);
Contracts:
Grants:
Distribution Statement:
Approved For Public Release
