Does the kappa opioid receptor system contribute to pain aversion?
Does the kappa opioid receptor system contribute to pain aversion?
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DOI：
10.3389/fphar.2014.00253
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发表时间：
2014
影响因子：
5.6
通讯作者：
Evans CJ
中科院分区：
文献类型：
--
作者：
Cahill CM;Taylor AM;Cook C;Ong E;Morón JA;Evans CJ
κ阿片受体（KOR）和内源性肽-配体强啡肽由于参与介导多种行为和神经生理反应而受到显著关注，包括对抗滥用药物（包括阿片类）的奖励性质。越来越多的证据表明，这个系统参与调节动机和情绪的状态。KOR的急性激活产生了逃避威胁的动机行为的增加，然而，与慢性应激相关的KOR激活导致了指示情绪障碍的症状的表达。公认KOR可以产生镇痛作用，并参与包括神经性疼痛在内的慢性疼痛状态。脊柱研究表明，KOR诱导的镇痛可逆转与周围神经损伤相关的疼痛超敏反应。虽然KOR激动剂的全身给药减弱了伤害性感觉传递，但这种作用似乎是应激诱导的作用，因为抗焦虑剂（包括δ阿片受体激动剂）减轻了KOR激动剂诱导的镇痛。此外，虽然KOR和强啡肽在驱动应激和药物戒断的烦躁和厌恶成分中的作用已经得到了很好的表征，但该系统如何介导与慢性疼痛相关的负面情绪状态相对未被探索。这篇综述提供的证据表明，强啡肽和KOR系统有助于疼痛的负性情感成分，这种受体系统可能有助于与慢性神经性疼痛相关的情绪障碍的高并发症。
The kappa opioid receptor (KOR) and the endogenous peptide-ligand dynorphin have received significant attention due the involvement in mediating a variety of behavioral and neurophysiological responses, including opposing the rewarding properties of drugs of abuse including opioids. Accumulating evidence indicates this system is involved in regulating states of motivation and emotion. Acute activation of the KOR produces an increase in motivational behavior to escape a threat, however, KOR activation associated with chronic stress leads to the expression of symptoms indicative of mood disorders. It is well accepted that KOR can produce analgesia and is engaged in chronic pain states including neuropathic pain. Spinal studies have revealed KOR-induced analgesia in reversing pain hypersensitivities associated with peripheral nerve injury. While systemic administration of KOR agonists attenuates nociceptive sensory transmission, this effect appears to be a stress-induced effect as anxiolytic agents, including delta opioid receptor agonists, mitigate KOR agonist-induced analgesia. Additionally, while the role of KOR and dynorphin in driving the dysphoric and aversive components of stress and drug withdrawal has been well characterized, how this system mediates the negative emotional states associated with chronic pain is relatively unexplored. This review provides evidence that dynorphin and the KOR system contribute to the negative affective component of pain and that this receptor system likely contributes to the high comorbidity of mood disorders associated with chronic neuropathic pain.
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