A nociceptive-intensity-dependent role for hydrogen sulphide in the formalin model of persistent inflammatory pain

Abstract

The present study investigated the hypothesis that hydrogen sulfide (H 2S) is pro-nociceptive in the formalin model of persistent inflammatory pain in the adult rat. Hind paw injection of formalin evoked a concentration-dependent increase in the hind paw concentration of H 2S. Increased concentration of H 2S was found in homogenates prepared from hind paws injected with 5% (but not 1.25%) formalin. Correspondingly, animal nociceptive flinching and hind paw edema were maximal with 5% formalin. Both nociceptive flinching and hind paw edema induced by injection of 5% formalin were attenuated by pretreatment with dl-propargylglycine (PPG; 50 mg/kg, i.p.) which is an inhibitor of the H 2S synthesizing enzyme cystathionine-γ-lyase (CSE). The effect of pretreatment with PPG was selective and the drug did not influence animal behavior or hind-paw edema with injection of 1.25% formalin. Furthermore, PPG pretreatment attenuated the induction of c-Fos in spinal laminae I–II following injection of 5% formalin. In contrast, co-injection of 1.25% formalin with sodium hydrogen sulfide (NaHS; 1 nmol/0.1 ml), a H 2S donor, into the hind paw increased animal nociceptive behavior. Collectively, these findings show that the effect of peripheral H 2S in the pathogenesis of inflammatory pain depends, at least in part, on the nociceptive intensity level.