Systemic tizanidine hydrochloride (Zanaflex (TM)) relieves thermal hyperalgesia in rats with an experimental mononeuropathy

We sought to determine whether tizanidine, an alpha2-agonist, relieved ther mal hyperalgesia in rats with surgically induced neuropathic pain. We used a Sprague-Dawley rat model in which a chronic constriction of the sciatic n erve caused the rats to develop postural changes, mechanical allodynia, and thermal hyperalgesia. Thermal hyperalgesia was verified through paw withdr awal latency (PWL). PWL was tested before surgery, after surgery, and after injections with tizanidine (0.5, 1.0, or 2.0 mg/kg) or normal saline. Ambu latory and total movements were evaluated by placing the rats in activity c ages. Thermal hyperalgesia was induced in all rats after surgery. Tizanidin e, but not saline, caused a significant improvement in PWL (P < 0.05), with complete reversal of thermal hyperalgesia at all doses on postoperative Da y 6. Rats who received tizanidine 2 mg/kg maintained complete reversal of t hermal hyperalgesia through postoperative Day 9. Some sedation was observed with tizanidine 2 mg/kg, but not with smaller doses. We conclude that tiza nidine effectively reversed thermal hyperalgesia in a rat model.