Pharmacological modulation of neuropathic pain-related depression of behavior: effects of morphine, ketoprofen, bupropion and [INCREMENT]9-tetrahydrocannabinol on formalin-induced depression of intracranial self-stimulation in rats.
Pharmacological modulation of neuropathic pain-related depression of behavior: effects of morphine, ketoprofen, bupropion and [INCREMENT]9-tetrahydrocannabinol on formalin-induced depression of intracranial self-stimulation in rats.
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DOI：
10.1097/fbp.0000000000000207
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发表时间：
2016-06
影响因子：
1.6
通讯作者：
Negus SS
中科院分区：
文献类型：
--
作者：
Leitl MD;Negus SS
神经性疼痛通常与行为抑郁症有关。足底注射福尔马林对大鼠颅内自我刺激（ICSS）产生持续的神经病相关性抑制。本研究评价了福尔马林诱导的ICSS抑制的药理学调节。在ICSS手术中，颅内电极靶向内侧前脑束的大鼠对脑电刺激有反应。双侧足底注射福尔马林可抑制ICSS 14天。评价吗啡（0.32-3.2 mg/kg）、酮洛芬（0.1-10 mg/kg）、安非他酮（3.2-32 mg/kg）和Δ9-四氢大麻酚（THC; 0.32-3.2 mg/kg）逆转福尔马林诱导的ICSS抑制的有效性。评价药物对福尔马林诱导的机械性异常性疼痛的作用以进行比较。吗啡和安非他酮逆转福尔马林诱导的ICSS抑郁症和机械性异常性疼痛，对ICSS的影响在重复治疗期间持续存在。酮洛芬未能逆转福尔马林效应。THC阻断了机械性异常性疼痛，但降低了对照组大鼠的ICSS，并加剧了福尔马林诱导的ICSS抑制。酮洛芬未能改变福尔马林效应表明福尔马林效应是由神经病变而非炎症引起的。吗啡和安非他酮逆转福尔马林效应的有效性与其他证据一致，即这些药物阻断大鼠的疼痛抑制行为并缓解人类的神经性疼痛。THC的作用表明一般行为抑制，不支持使用THC治疗神经性疼痛。
Neuropathic pain is often associated with behavioral depression. Intraplantar formalin produces sustained, neuropathy-associated depression of intracranial self-stimulation (ICSS) in rats. This study evaluated pharmacological modulation of formalin-induced ICSS depression. Rats with intracranial electrodes targeting the medial forebrain bundle responded for electrical brain stimulation in an ICSS procedure. Bilateral intraplantar formalin administration depressed ICSS for 14 days. Morphine (0.32–3.2 mg/kg), ketoprofen (0.1–10 mg/kg), bupropion (3.2–32 mg/kg), and Δ9-tetrahydrocannabinol (THC; 0.32–3.2 mg/kg) were evaluated for their effectiveness to reverse formalin-induced depression of ICSS. Drug effects on formalin-induced mechanical allodynia were evaluated for comparison. Morphine and bupropion reversed both formalin-induced ICSS depression and mechanical allodynia, and effects on ICSS were sustained during repeated treatment. Ketoprofen failed to reverse either formalin effect. THC blocked mechanical allodynia, but decreased ICSS in control rats and exacerbated formalin-induced depression of ICSS. The failure of ketoprofen to alter formalin effects suggests that formalin effects result from neuropathy rather than inflammation. The effectiveness of morphine and bupropion to reverse formalin effects agrees with other evidence that these drugs block pain-depressed behavior in rats and relieve neuropathic pain in humans. The effects of THC suggest general behavioral suppression and do not support the use of THC to treat neuropathic pain.