The effect of systemic zonisamide (Zonegran) on thermal hyperalgesia and mechanical allodynia in rats with an experimental mononeuropathy

Abstract

We studied the ability of zonisamide (Zonegran) to relieve thermal hyperalgesia and/or mechanical allodynia in the chronic constriction injury model of neuropathic pain. Zonisamide (25, 50, or 100 mg/kg) or saline was administered in a blinded, randomized manner by intraperitoneal injection on postoperative days (PODs) 4, 5, and 6. Paw withdrawal latency (PWL) to heat, paw withdrawal response to von Frey monofilaments, and pain scores based on weight-bearing were tested: before surgery; before and after zonisamide or saline (PODs 4, 5, and 6); and on POD 9. Systemic zonisamide relieved thermal hyperalgesia in a dose-dependent manner. All PWLs were significantly increased after zonisamide administration compared with pre-zonisamide measurements, except with the 100 mg/kg dose on POD 5. After zonisamide 100 mg/kg administration, there was a sustained increase in PWL on PODs 5 and 9, with significant carryover effect from the previous dose. However, zonisamide had little effect on mechanical allodynia, except at the 100 mg/kg dose, which was sedating in the rat. At the 100 mg/kg dose, paw withdrawal response was increased on PODs 4 and 5, whereas pain scores were reduced on PODs 4, 5, and 6. Pain scores were inconsistently reduced after 50 mg/kg or 25 mg/kg doses.

Implications: Zonisamide causes a dose-related decrease in heat sensitivity in a rat model of neuropathic pain, but relieves mechanical sensitivity only in a dose that is sedating to the rat. Zonisamide may be useful in the treatment of some types of neuropathic pain.