Center for Neuropharmacology and Neuroscience, Albany Medical College MC-136, 47 New Scotland Avenue, Albany, NY 12208, USA.
Brain Res. 2011 Nov 18;1424:32-7. doi: 10.1016/j.brainres.2011.10.002. Epub 2011 Oct 8.
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 μg) 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 μg) 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.
非阿片类镇痛药 Improgan 已知在啮齿动物脑干中发挥作用,可在几种急性疼痛测试中产生高效的镇痛作用。然而,尚未在任何慢性疼痛模型中研究 Improgan。为了评估 Improgan 在神经病理性疼痛动物模型中的疗效,研究了该药物在大鼠单侧脊神经结扎 (SNL) 后机械性痛觉过敏中的作用。脑室内 (icv) Improgan(40-80μg)给药后 1 小时内完全、可逆、剂量依赖性地减轻后爪机械性痛觉过敏,无明显的行为或运动副作用。将 Improgan(5-30μg)脑内(ic)微量注射到延髓头端腹内侧区 (RVM) 也可逆转痛觉过敏,表明该脑区是 Improgan 作用的重要部位。最近证明 Improgan 抑制 RVM ON 细胞活性可能解释了目前观察到的抗痛觉过敏活性。目前的研究结果表明,为人类开发的穿透性脑的类似 Improgan 的药物可能是治疗神经病理性疼痛的有效药物。