Hydrogen sulphide induces micro opioid receptor-dependent analgesia in a rodent model of visceral pain.

Background: Hydrogen sulphide (H2S) is a gaseous neuro-mediator that exerts analgesic effects in rodent models of visceral pain by activating KATP channels. A body of evidence support the notion that K AT P channels interact with endogenous opioids. Whether H2 S-induced analgesia involves opioid receptors is unknown. Methods: The perception of painful sensation induced by colorectal distension (CRD) in conscious rats was measured by assessing the abdominal withdrawal reflex. The contribution of opioid receptors to H2 S-induced analgesia was investigated by administering rats with selective μ, κ and δ opioid receptor antagonists and antisenses. To investigate whether H2 S causes μ opioid receptor (MOR) transactivation, the neuronal like ce lls SKNMCs were challenged with H2S in the presence of MOR agonist (DAMGO) or antagonist (CTAP). MOR activation and phosphorylation, its association to β arrestin and internalization were measured. Results: H2S exerted a potent analgesic effects on CRD-induced pain. H2S-induced analgesia required the activation of the opioid system. By pharmacological and molecular analyses, a robust inhibition of H 2 S-induced analgesia was observed in response to cent ral administration of CTAP an d MOR antisense, while κ and δ receptors were less involved. H 2 S caused MOR transactivation and internalization in SKNMCs by a mechanism that required AKT phosphorylation. MOR transactivation was inhibited by LY294002, a PI3K inhibitor, and glibenclamide, a KATP channels blocker. Conclusions: This study provides pharmacological and molecular evidence that antinociception exerted by H2S in a rodent model of visceral pain is modulated by the transa ctivation of MOR. This obse rvation provides support for development of new pharmacological approaches to visceral pain.