Department of Pharmacology and Pharmacotherapy, Medical School & Centre for Neuroscience, University of Pécs, 12 Szigeti Street, H-7624, Pécs, Hungary; National Laboratory for Drug Research and Development, Budapest, Hungary; Hungarian Research Network, Chronic Pain Research Group, Pécs, Hungary.
Department of Pharmacology and Pharmacotherapy, Medical School & Centre for Neuroscience, University of Pécs, 12 Szigeti Street, H-7624, Pécs, Hungary; National Laboratory for Drug Research and Development, Budapest, Hungary; Hungarian Research Network, Chronic Pain Research Group, Pécs, Hungary.
Curr Opin Pharmacol. 2024 Apr;75:102432. doi: 10.1016/j.coph.2024.102432. Epub 2024 Jan 30.
Chronic pain conditions are unmet medical needs, since the available drugs, opioids, non-steroidal anti-inflammatory/analgesic drugs and adjuvant analgesics do not provide satisfactory therapeutic effect in a great proportion of patients. Therefore, there is an urgent need to find novel targets and novel therapeutic approaches that differ from classical pharmacological receptor antagonism. Most ion channels and receptors involved in pain sensation and processing such as Transient Receptor Potential ion channels, opioid receptors, P2X purinoreceptors and neurokinin 1 receptor are located in the lipid raft regions of the plasma membrane. Targeting the membrane lipid composition and structure by sphingolipid or cholesterol depletion might open future perspectives for the therapy of chronic inflammatory, neuropathic or cancer pain, most importantly acting at the periphery.
慢性疼痛状况是未满足的医疗需求,因为现有的药物(阿片类药物、非甾体抗炎/镇痛药和辅助镇痛药)在很大一部分患者中无法提供令人满意的治疗效果。因此,迫切需要寻找新的靶点和新的治疗方法,这些方法与经典的药理学受体拮抗作用不同。大多数参与疼痛感觉和处理的离子通道和受体,如瞬时受体电位离子通道、阿片受体、P2X 嘌呤能受体和神经激肽 1 受体,都位于质膜的脂筏区域。通过鞘脂或胆固醇耗竭来靶向细胞膜脂质组成和结构,可能为治疗慢性炎症性、神经性或癌性疼痛开辟新的前景,最重要的是在外周发挥作用。