Naturally occurring glucosinolates and isothiocyanates as a weapon against chronic pain: potentials and limits

Investigation into glucosinolates (GLs) therapeutic effects boasts a long history, which began with the evidence that their hydrolysis-derived isothiocyanates (ITCs) could exert cytoprotective effects through the modulation of both the inflammatory response (NF-kB pathway) and the oxidative stress (Nrf2/ARE pathway), two processes largely involved in the pathogenesis of chronic pain syndromes. GLs and ITCs are also able to modulate the activity and the expression of several targets involved in pain regulation, like opioid receptors. Recently, ITCs turned out to be slow-H2S donors in vivo, able to directly modulate the activity of a subtype of K(V)7 potassium channels involved in the transmission of painful stimuli, providing a further incentive to their employment in pain management. Nevertheless, some controversies exist in the use of ITCs for pain relief considering their ability to positively modulate the activity of TRPA1 receptors. This review focuses on the preclinical and clinical evidence attesting the beneficial effects of GLs and their derivatives ITCs in chronic inflammatory and neuropathic conditions. In this context, the mechanisms underlying the ability of GLs and ITCs to modulate pain perception and, besides, to prevent the establishment of chronic pain will be described along with their pharmacokinetics and toxicological profile. Finally, other possible mechanisms hidden behind GLs efficacy on pain will be discussed.