EFFECTS OF TREATMENT WITH HYDROGEN SULFIDE-RELEASING MOLECULES ON THE NOCICEPTIVE AND DEPRESSIVE-LIKED RESPONSES ACCOMPANYING PERSISTENT NEUROPATHIC PAIN IN MICE

L. Cabarga1,2, G. Batallé1,2, O. Pol1,2 

1Institut d'Investigació Biomèdica Sant Pau. Hospital de la Santa Creu i Sant Pau, Grup de Neurofarmacologia Molecular, Barcelona, Spain, 2Institut de Neurociències, Universitat Autònoma de Barcelona, Barcelona, Spain

Background and aims: Therapies to treat persistent neuropathic pain and the emotional disorders associated are limited with modest efficacy. In this study, we examined if treatment with two slow releasing hydrogen sulfide (H2S) donors, allyl isothiocyanate (A-ITC) and phenyl isothiocyanate (P-ITC), alleviates chronic neuropathic pain and the depressive-like behaviors associated. Their antioxidants properties were also evaluated.
Methods: In C57BL/6 male mice with neuropathic pain and depressive-like behaviors induced by the chronic constriction of sciatic nerve (CCI) we evaluated the mechanical anti-allodynic, thermal anti-hyperalgesic, thermal anti-allodynic and the antidepressant effects of A-ITC and P-ITC intraperitoneally administered. We also assessed the effect of these treatments on the expression of heme oxygenase 1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1) in the spinal cord.
Results: Data demonstrated that while acute administration of A-ITC and P-ITC is sufficient to block thermal hypersensitivity, chronic administration are needed to inhibit the mechanical and thermal allodynia induced by CCI. Both H2S donors reduced the depressive-like behaviors accompanying persistent neuropathic pain and increased the spinal cord expression of HO-1 and NQO1.
Conclusions: Our results revealed the differential regulation of the allodynia and hyperalgesia induced by A-ITC and P-ITC and demonstrated the antidepressant and antioxidant properties of these compounds in neuropathic pain. Thus, this study proposes A-ITC and P-ITC as alternatives for the treatment of persistent neuropathic pain and comorbidities associated.

This work was supported by Ministerio de Ciencia, Innovación y Universidades, Instituto de Salud Carlos III, Spain and Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea [Grant: PI1800645].

EFFECTS OF TREATMENT WITH HYDROGEN SULFIDE-RELEASING MOLECULES ON THE NOCICEPTIVE AND DEPRESSIVE-LIKE RESPONSES ACCOMPANYING PERSISTENT NEUROPATHIC PAIN IN MICE