Efficacy of isothiocyanate-based compounds on different forms of persistent pain

Purpose: Current pharmacotherapy for persistent pain related to neuropathy or articular diseases is unsatisfactory, due to the large number of unresponsive patients and side effects. Isothiocyanates (ITCs) arc a class of natural or synthetic compounds characterized by the general formula R-NCS. ITCs show antihyperalgesic effects in models of central and peripheral nervous tissue injury and anti-inflammatory properties. The pharmacodynamics arc strictly related to the release of the gasotransmitter hydrogen sulfide (H2S) from their moiety. In particular, phenyl ITC (PITC) and 3-carboxyphenyl ITC (3C-PITC) exhibit interesting slow H2S-release properties suitable for treating painful pathology. The aim of the present work was to evaluate the efficacy of PITC and 3C-PITC against mechanical hyperalgesia and spontaneous pain induced by nerve injury and osteoarthritis. Methods: Nerve injury and osteoarthritis were induced in rats by ligation of the sciatic nerve (chronic constriction injury) and intra-articular injection of monoiodoacetate, respectively. Behavioral tests were performed 14 days after damage induction. Results: Single subcutaneous administrations of PITC, 3C-PITC (4.43 and 13.31 gmol kg(-1), respectively) were able to completely reverse hypersensitivity to noxious stimuli in both models of neuropathic and osteoarticular pain. The effect of ITCs was compared with that of NaHS, the prototypical H2S donor, showing similar efficacy and higher potency. ITCs and NaHS also reduced spontaneous pain. Conclusion: ITCs offer a promising novel approach to counteract persistent, drug-resistant painful pathology.