THE ANTINOCICEPTIVE AND ANTIDEPRESSANT EFFECTS OF SLOW RELEASING HYDROGEN SULFIDE DONORS IN ANIMALS WITH CHRONIC OSTEOARTHRITIC PAIN 

G. Batallé1,2, L. Cabarga1,2, 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: Osteoarthritis and their comorbidities associated, such as depression, is an important clinical problem which have a negative impact in the quality of life of patients. In this study, we investigated if the systemic administration of two slow releasing hydrogen sulfide (H2S) donors, allyl isothiocyanate (A-ITC) and phenyl isothiocyanate (P-ITC), alleviates chronic osteoarthritic pain and the depressive-like behaviors associated. The possible mechanisms implicated were also assessed.
Methods: In C57BL/6 female mice with osteoarthritic pain induced by the knee injection of monosodium iodoacetate (MIA) we evaluated the effects of the repeated administration of A-ITC and P-ITC on: 1) the mechanical allodynia, thermal nociception, grip strength deficit and depressive-like behaviors caused by MIA and 2) the protein levels of heme oxygenase 1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1) in the spinal cord.
Results: The repeated administration of A-ITC and P-ITC inhibited the mechanical and thermal hypersensitivity and the grip strength deficit produced by MIA. Both treatments also inhibited the depressive-like behaviors and enhanced the expression of HO-1 and NQO1 in the spinal cord of animals with osteoarthritic pain.
Conclusions: This study revealed the antinociceptive, antidepressant and antioxidant effects of A-ITC and P-ITC and suggested that treatment with slow releasing H2S compounds may represent an interesting target for the treatment of chronic osteoarthritic pain and the depressive-like behaviors associated.

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