Fight fire with fire: Neurobiology of capsaicin-induced analgesia for chronic pain.
Fight fire with fire: Neurobiology of capsaicin-induced analgesia for chronic pain.
复制标题
以火还火：辣椒素治疗慢性疼痛的神经生物学。
DOI：
10.1016/j.pharmthera.2020.107743
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发表时间：
2021-04
影响因子：
13.5
通讯作者：
Chung MK
中科院分区：
文献类型：
--
作者：
Arora V;Campbell JN;Chung MK
辣椒素是辣椒中的辛辣成分，会给人类带来强烈的灼痛感。辣椒素选择性激活瞬态受体电位香草酸 1 (TRPV1)，该受体富含伤害性初级传入神经，并支持辣椒素引起的灼痛机制。矛盾的是，辣椒素长期以来一直被用作镇痛剂。含有辣椒素的局部贴剂和注射制剂的开发已在临床环境中用于治疗慢性疼痛，例如神经性疼痛，并具有治疗骨关节炎的潜力。更详细地确定辣椒素诱导镇痛的神经生物学机制应该为辣椒素治疗提供逻辑依据，并有助于克服治疗的局限性，其中包括治疗结果的个体差异和手术不适。低浓度的辣椒素会导致伤害感受器末端的短期功能丧失。这种现象在数小时内即可逆转，因此可能无法解释临床益处。相比之下，高浓度的辣椒素会导致表达 TRPV1 的传入末梢消融介导的长期去功能化，从而导致持续数月的长效镇痛。最近的研究表明，辣椒素诱导的 Ca2+/钙蛋白酶介导的轴突末梢消融对于在神经性疼痛小鼠模型中产生持久镇痛是必要的。与钙蛋白酶结合，轴突线粒体功能障碍和微管紊乱也可能导致辣椒素的长期影响。随着时间的推移，镇痛效果随着消融传入神经末梢的再生而减弱。进一步确定辣椒素诱导镇痛的神经生物学机制应该会产生更有效的非阿片类镇痛药物，并且副作用更少。
Capsaicin, the pungent ingredient in chili peppers, produces intense burning pain in humans. Capsaicin selectively activates the transient receptor potential vanilloid 1 (TRPV1), which is enriched in nociceptive primary afferents, and underpins the mechanism for capsaicin-induced burning pain. Paradoxically, capsaicin has long been used as an analgesic. The development of topical patches and injectable formulations containing capsaicin has led to application in clinical settings to treat chronic pain conditions, such as neuropathic pain and the potential to treat osteoarthritis. More detailed determination of the neurobiological mechanisms of capsaicin-induced analgesia should provide the logical rationale for capsaicin therapy and help to overcome the treatment’s limitations, which include individual differences in treatment outcome and procedural discomfort. Low concentrations of capsaicin induce short-term defunctionalization of nociceptor terminals. This phenomenon is reversible within hours and, hence, likely does not account for the clinical benefit. By contrast, high concentrations of capsaicin lead to long-term defunctionalization mediated by the ablation of TRPV1-expressing afferent terminals, resulting in long-lasting analgesia persisting for several months. Recent studies have shown that capsaicin-induced Ca2+/calpain-mediated ablation of axonal terminals is necessary to produce long-lasting analgesia in a mouse model of neuropathic pain. In combination with calpain, axonal mitochondrial dysfunction and microtubule disorganization may also contribute to the longer-term effects of capsaicin. The analgesic effects subside over time in association with the regeneration of the ablated afferent terminals. Further determination of the neurobiological mechanisms of capsaicin-induced analgesia should lead to more efficacious non-opioidergic analgesic options with fewer adverse side effects.
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影响因子：
5.7
作者：
Aasvang, Eske K.;Hansen, Jeanette B.;Kehlet, Henrik
通讯作者：
Kehlet, Henrik
影响因子：
2.7
作者：
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通讯作者：
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DOI：
10.1523/jneurosci.4065-10.2011
发表时间：
2011-01-19
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
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通讯作者：
Court FA
影响因子：
--
作者：
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通讯作者：
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影响因子：
48
作者：
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通讯作者：
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