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

Abstract

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 KV7 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.

The Efficacy of Camelina sativa Defatted Seed Meal against Colitis-Induced Persistent Visceral Hypersensitivity: The Relevance of PPAR α Receptor Activation in Pain Relief

“…To date, many plant-derived products have been studied with the aim of combining different mechanisms of action to improve the therapy for post-inflammatory intestinal hyperalgesia, which is supported by inflammatory, neuropathic, and immune mechanisms [ 1 , 8 ]. In this context, Brassicaceae plants emerged to be ideal candidates, since the ITCs contained in these plants can modulate both inflammatory response and oxidative stress [ 9 , 10 ]; they also display potential benefits for the gut microbiota [ 12 , 13 , 14 , 56 ], which has high relevance in gut pain associated with colitis [ 17 , 57 , 58 ]. Several studies in the literature attest that ITCs are effective against both inflammatory and neuropathic pain by the slow release of H 2 S in vivo , and by the positive modulation of Kv7 potassium channels activity [ 18 , 20 , 21 , 25 , 59 ], which are involved in different physiological processes like the regulation of blood pressure and the transmission of painful stimuli [ 11 , 19 , 60 , 61 , 62 ].…”

“…Anyway, it is important to take in account that other phytochemicals, like the GSLs and the flavonoids, have a neuroprotective potential [ 9 , 18 ] that might involve PPAR-α and/or be completely independent from the modulation of these receptors. Interestingly, flavonoids such as naringenin can modulate the activation of PPAR-α [ 68 , 81 , 82 ], while GSLs and ITCs are reported to act on the signalling pathways modulated by PPAR-α, such as related to NF-kB [ 9 , 71 , 72 ]. This convergence might potentiate the effect of Camelina sativa ’s constituents on the intestinal damage.…”

“…Visceral hyperalgesia resulting from colitis has a complex nature with inflammatory, neuropathic, and immune components [ 1 , 8 ]. The broad range of beneficial effects shown by Brassicaceae constituents, such as the glucosinolates (GSLs) [ 9 , 10 ], raised our interest in studying the potential of employing these plants in the therapy for gastrointestinal pain. Indeed, the main derivatives of GSL hydrolysis, isothiocyanates (ITCs), have been reported to modulate both inflammatory processes and oxidative stress [ 10 , 11 ], two factors contributing to the development of chronic pain in patients [ 3 , 6 , 12 , 13 ].…”

Editorial to the special issue: “Phytochemicals in nutrition and health: advances and challenges”

“…Their hydrolysis by myrosinase leads to a series of bioactive breakdown products such as isothiocyanates (ITCs). Lucarini et al ( 2022 ) aim to describe the preclinical and clinical evidence supporting the beneficial effects of GLs and ITCs in chronic inflammatory and neuropathic conditions. In particular, they illustrate their efficacy to modulate the activity and expression of several pharmacological targets, like opioid receptors, involved in pain regulation.…”