Abstract
Humans have used opioids to suppress moderate to severe pain for thousands of years. However, the long-term use of opioids has several adverse effects, such as opioid tolerance, opioid-induced hyperalgesia, and addiction. In addition, the low efficiency of opioids in controlling neuropathic pain limits their clinical applications. Combining nonopioid analgesics with opioids to target multiple sites along the nociceptive pathway may alleviate the side effects of opioids. This study reviews the feasibility of reducing opioid side effects by regulating the transient receptor potential vanilloid 1 (TRPV1) receptors and summarizes the possible underlying mechanisms. Blocking and activating TRPV1 receptors can improve the therapeutic profile of opioids in different manners. TRPV1 and μ-opioid receptors are bidirectionally regulated by β-arrestin2. Thus, drug combinations or developing dual-acting drugs simultaneously targeting μ-opioid and TRPV1 receptors may mitigate opioid tolerance and opioid-induced hyperalgesia. In addition, TRPV1 receptors, especially expressed in the dorsal striatum and nucleus accumbens, participate in mediating opioid reward, and its regulation can reduce the risk of opioid-induced addiction. Finally, co-administration of TRPV1 antagonists and opioids in the primary action sites of the periphery can significantly relieve neuropathic pain. In general, the regulation of TRPV1 may potentially ameliorate the side effects of opioids and enhance their analgesic efficacy in neuropathic pain.
Funder
National Natural Science Foundation of China
Scientific Foundation of Institute of Psychology, Chinese Academy of Science
Subject
Health, Toxicology and Mutagenesis,Public Health, Environmental and Occupational Health
Cited by
4 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献