Department of Pharmacodynamics, Jagiellonian University, Medical College, Medyczna 9, 30-688 Cracow, Poland.
Curr Med Chem. 2013;20(11):1409-36. doi: 10.2174/09298673113209990107.
In mammals several members of the Transient Receptor Potential channel family (TRPs), expressed mainly in the sensory neurons and skin keratinocytes, are implicated in relevant physiological functions, including thermosensation,nociception and vision. Since the TRPV1-4, TRPA1 and TRPM8 channels from this family play a pivotal role in both the detection and possibly modulation of painful stimuli, they are regarded as a very promising target of novel analgesic drugs. A few agents acting at TRPs, such as capsaicin or menthol, have a long history of their application as analgesics,whereas others (e.g. SB705498, JTS653, JNJ17203212, AP18, A967079, Chembridge-5861528 or PBMC) are currently being evaluated both in animals and in humans. In this review we discuss pain physiology, as well as the pharmacological properties of the TRPs involved in pain detection as potential critical peripheral analgesic targets. We present one of the most relevant strategies in the search for novel analgesic drugs, namely the TRP channels and their ligands, both agonists and antagonists as potential novel therapeutics for inflammatory and neuropathic pain syndromes. The safety profile of these agents, in particular their impact on thermosensation, is also discussed below.
在哺乳动物中，瞬时受体电位通道家族（TRP）的几个成员主要在感觉神经元和皮肤角质形成细胞中表达，与相关的生理功能有关，包括热感觉、伤害感受和视觉。由于该家族中的 TRPV1-4、TRPA1 和 TRPM8 通道在痛觉刺激的检测和可能的调节中起着关键作用，因此它们被认为是新型镇痛药物的一个非常有前途的靶点。一些作用于 TRP 的药物，如辣椒素或薄荷醇，在作为镇痛药方面有着悠久的历史，而其他药物（如 SB705498、JTS653、JNJ17203212、AP18、A967079、Chembridge-5861528 或 PBMC）目前正在动物和人体中进行评估。在这篇综述中，我们讨论了疼痛生理学，以及参与疼痛检测的 TRP 的药理学特性，作为潜在的关键外周镇痛靶点。我们提出了寻找新型镇痛药物的一种最相关策略，即 TRP 通道及其配体，作为治疗炎症和神经病理性疼痛综合征的潜在新型治疗方法，包括激动剂和拮抗剂。还讨论了这些药物的安全性概况，特别是它们对热感觉的影响。
