Journal
LIFE SCIENCES
Volume 314, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2022.121302
Keywords
Neuropathic pain; Fibromyalgia; Bradykinin; Cancer; Inflammatory pain; Nociplastic pain
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Kinins are endogenous peptides that play an essential role in physiological and pathological processes by activating two transmembrane receptors. This review summarizes the current understanding of the involvement of kinin receptors and their potential therapeutic applications in various painful conditions. The pharmacological actions and clinical potential of kinin receptor antagonists and other targeting molecules are also discussed.
Kinins are endogenous peptides that belong to the kallikrein-kinin system, which has been extensively studied for over a century. Their essential role in multiple physiological and pathological processes is demonstrated by activating two transmembrane G-protein-coupled receptors, the kinin B-1 and B-2 receptors. The attention is mainly given to the pathological role of kinins in pain transduction mechanisms. In the past years, a wide range of preclinical studies has amounted to the literature reinforcing the need for an updated review about the participation of kinins and their receptors in pain disorders. Here, we performed an extensive literature search since 2004, describing the historical progress and the current understanding of the kinin receptors' participation and its potential therapeutic in several acute and chronic painful conditions. These include inflammatory (mainly arthritis), neuropathic (caused by different aetiologies, such as cancer, multiple sclerosis, antineoplastic toxicity and diabetes) and nociplastic (mainly fibromyalgia) pain. Moreover, we highlighted the pharmacological actions and possible clinical applications of the kinin B-1 and (B)2 receptor antagonists, kallikrein inhibitors or kallikrein-kinin system signalling pathways-target molecules in these different painful conditions. Notably, recent findings sought to elucidate mechanisms for guiding new and better drug design targeting kinin B-1 and B-2 receptors to treat a disease diversity. Since the kinin B-2 receptor antagonist, Icatibant, is clinically used and well-tolerated by patients with hereditary angioedema gives us hope kinin receptors antagonists could be more robustly tested for a possible clinical application in the treatment of pathological pains, which present limited pharmacology management.
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