Catechol-O-methyltransferase inhibition alters pain and anxiety-related volitional behaviors through activation of β-adrenergic receptors in the rat.
Catechol-O-methyltransferase inhibition alters pain and anxiety-related volitional behaviors through activation of β-adrenergic receptors in the rat.
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DOI：
10.1016/j.neuroscience.2015.01.064
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发表时间：
2015-04-02
期刊：
影响因子：
3.3
通讯作者：
Nackley, A. G.
中科院分区：
文献类型：
--
作者：
Kline, R. H.;Exposto, F. G.;O'Buckley, S. C.;Westlund, K. N.;Nackley, A. G.
由遗传变异或药理学消耗引起的儿茶酚-O-甲基转移酶（COMT）活性降低导致人类疼痛感知增强和动物伤害性行为增强。使用阶段性机械和热反射试验（例如von Frey，Hargreaves），最近的研究表明，大鼠的急性COMT依赖性疼痛由β-肾上腺素能受体（β AR）介导。为了更接近地模拟与COMT长期减少相关的人类慢性疼痛状况的特征，本研究试图使用操作性10-45°C热位置偏好任务和亮/暗偏好测试来确定持续以及急性COMT抑制后的意志性疼痛相关和焦虑样行为反应。此外，我们试图通过测量腹部区域的触觉感觉阈值来评估持续COMT抑制对全身疼痛的影响。结果表明，COMT抑制剂OR 486的急性和持续给药增加了响应于热的疼痛行为。此外，持续施用OR 486增加了响应于强光的焦虑行为以及腹部机械感觉。最后，所有疼痛相关行为均被非选择性βAR拮抗剂普萘洛尔阻断。总的来说，这些发现提供了第一个证据，即急性或慢性COMT抑制后刺激AR会驱动与影响多个身体部位的疼痛加剧相关的认知情感行为。
Reduced catechol-O-methyltransferase (COMT) activity resulting from genetic variation or pharmacological depletion results in enhanced pain perception in humans and nociceptive behaviors in animals. Using phasic mechanical and thermal reflex tests (e.g. von Frey, Hargreaves), recent studies show that acute COMT-dependent pain in rats is mediated by β-adrenergic receptors (βARs). In order to more closely mimic the characteristics of human chronic pain conditions associated with prolonged reductions in COMT, the present study sought to determine volitional pain-related and anxiety-like behavioral responses following sustained as well as acute COMT inhibition using an operant 10–45°C thermal place preference task and a light/dark preference test. In addition, we sought to evaluate the effects of sustained COMT inhibition on generalized body pain by measuring tactile sensory thresholds of the abdominal region. Results demonstrated that acute and sustained administration of the COMT inhibitor OR486 increased pain behavior in response to thermal heat. Further, sustained administration of OR486 increased anxiety behavior in response to bright light, as well as abdominal mechanosensation. Finally, all pain-related behaviors were blocked by the non-selective βAR antagonist propranolol. Collectively, these findings provide the first evidence that stimulation of ARs following acute or chronic COMT inhibition drives cognitive-affective behaviors associated with heightened pain that affects multiple body sites.
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