Characterization of a mouse neuropathic pain model caused by the highly active antiviral therapy (HAART) Stavudine.

Abstract

BACKGROUND\nAlthough highly active antiviral therapies (HAART) exert control over viral replication in persons with Acquired Immunodeficiency Syndrome (AIDS), neuropathic pain is a side effect. Symptoms include hyperalgesia and allodynia. Stavudine, also known as D4T, is a HAART used to treat Human Immunodeficiency Virus (HIV). This study examined the extent to which D4T produces neuropathic pain and examined pharmacological management with a standard opioid analgesic.\n\n\nMETHODS\nMale and female C57BL/6\xa0J mice were injected intraperitoneally with one dose of vehicle or D4T (10-56\xa0mg/kg). Mice were tested through day 92 post injection for mechanical allodynia, assessed with von Frey filaments, and thermal hyperalgesia, assessed via the hotplate test. Separate cohorts received vehicle or 56\xa0mg/kg D4T, the presence of allodynia and thermal hyperalgesia confirmed, and mice received intraperitoneal vehicle, morphine, or 0.032\xa0mg/kg naltrexone\u2009+\u2009morphine.\n\n\nRESULTS\nD4T produced dose- and time-dependent mechanical allodynia and thermal hyperalgesia. The smallest effective D4T dose was 17.8\xa0mg/kg. This dose produced mechanical allodynia but not thermal hyperalgesia. Larger D4T doses (32 and 56\xa0mg/kg) produced mechanical allodynia and thermal hyperalgesia lasting 92\xa0days. Morphine dose-dependently alleviated both mechanical allodynia and thermal hyperalgesia in D4T-treated mice with ED50 values of 4.4 and 1.2\xa0mg/kg, respectively. Naltrexone produced a rightward shift of the morphine dose-response function, i.e., increased the ED50 value of morphine by at least 3.8-fold.\n\n\nCONCLUSION\nStavudine produced neuropathic pain as a function of dose and time in mice. Opioid analgesics appear to be effective in alleviating neuropathic pain in a D4T-induced mouse model.