Improgan, a non-opioid analgesic, is known to act in the rodent brain stem to produce highly effective antinociception in several acute pain tests. However, improgan has not been studied in any models of chronic pain. To assess the efficacy of improgan in an animal model of neuropathic pain, the effects of this drug were studied on mechanical allodynia following unilateral spinal nerve ligation (SNL) in rats. Intracerebroventricular (icv) improgan (40-80 mug) produced complete, reversible, dose-dependent attenuation of hind paw mechanical allodynia for up to 1h after administration, with no noticeable behavioral or motor side effects. Intracerebral (ic) microinjections of improgan (5-30 mug) into the rostral ventromedial medulla (RVM) also reversed the allodynia, showing this brain area to be an important site for improgan's action. The recently-demonstrated suppression of RVM ON-cell activity by improgan may account for the presently-observed anti-allodynic activity. The present findings suggest that brain-penetrating, improgan-like drugs developed for human use could be effective medications for the treatment of neuropathic pain.
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