DEET potentiates the development and persistence of anticholinesterase dependent chronic pain signs in a rat model of Gulf War Illness pain
| Autor: | T.J. Nutter, Richard D. Johnson, L.K. Flunker, Brian Y. Cooper |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Rat model DEET Hindlimb Toxicology Gulf war Persistence (computer science) Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals Persian Gulf Syndrome Pain Measurement Pharmacology business.industry Chronic pain Drug Synergism medicine.disease Rats Disease Models Animal 030104 developmental biology chemistry Anesthesia Insect Repellents Nociceptor Pyridostigmine Bromide Cholinesterase Inhibitors Chronic Pain business 030217 neurology & neurosurgery |
| Zdroj: | Toxicology and applied pharmacology. 316 |
| ISSN: | 1096-0333 |
| Popis: | Exposure to DEET (N,N-diethyl-meta-toluamide) may have influenced the pattern of symptoms observed in soldiers with GWI (Gulf War Illness; Haley and Kurt, 1997). We examined how the addition of DEET (400 mg/kg; 50% topical) to an exposure protocol of permethrin (2.6 mg/kg; topical), chlorpyrifos (CP; 120 mg/kg), and pyridostigmine bromide (PB;13 mg/kg) altered the emergence and pattern of pain signs in an animal model of GWI pain ( Nutter et al., 2015 ). Rats underwent behavioral testing before, during and after a 4 week exposure: 1) hindlimb pressure withdrawal threshold; 2) ambulation (movement distance and rate); and 3) resting duration. Additional studies were conducted to assess the influence of acute DEET (10–100 μM) on muscle and vascular nociceptor K v 7, K DR , Na v 1.8 and Na v 1.9. We report that a 50% concentration of DEET enhanced the development and persistence of pain-signs. Rats exposed to all 4 compounds exhibited ambulation deficits that appeared 5–12 weeks post-exposure and persisted through weeks 21–24. Rats exposed to only three agents (CP or PB excluded), did not fully develop ambulation deficits. When PB was excluded, rats also developed rest duration pain signs, in addition to ambulation deficits. There was no evidence that physiological doses of DEET acutely modified nociceptor K v 7, K DR , Na v 1.8 or Na v 1.9 activities. Nevertheless, DEET augmented protocols decreased the conductance of K v 7 expressed in vascular nociceptors harvested from chronically exposed rats. We concluded that DEET enhanced the development and persistence of pain behaviors, but the anticholinesterases CP and PB played a determinant role. |
| Databáze: | OpenAIRE |
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