Hydrogen sulphide induces μ opioid receptor-dependent analgesia in a rodent model of visceral pain
<p>Abstract</p> <p>Background</p> <p>Hydrogen sulphide (H<sub>2</sub>S) is a gaseous neuro-mediator that exerts analgesic effects in rodent models of visceral pain by activating K<sub>ATP </sub>channels. A body of evidence support the notion that...
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| Main Authors: | , , , , , , |
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| Format: | Book |
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SAGE Publishing,
2010-06-01T00:00:00Z.
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| Summary: | <p>Abstract</p> <p>Background</p> <p>Hydrogen sulphide (H<sub>2</sub>S) is a gaseous neuro-mediator that exerts analgesic effects in rodent models of visceral pain by activating K<sub>ATP </sub>channels. A body of evidence support the notion that K<sub>ATP </sub>channels interact with endogenous opioids. Whether H<sub>2</sub>S-induced analgesia involves opioid receptors is unknown.</p> <p>Methods</p> <p>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 H<sub>2</sub>S-induced analgesia was investigated by administering rats with selective μ, κ and δ opioid receptor antagonists and antisenses. To investigate whether H<sub>2</sub>S causes μ opioid receptor (MOR) transactivation, the neuronal like cells SKNMCs were challenged with H<sub>2</sub>S in the presence of MOR agonist (DAMGO) or antagonist (CTAP). MOR activation and phosphorylation, its association to β arrestin and internalization were measured.</p> <p>Results</p> <p>H<sub>2</sub>S exerted a potent analgesic effects on CRD-induced pain. H<sub>2</sub>S-induced analgesia required the activation of the opioid system. By pharmacological and molecular analyses, a robust inhibition of H<sub>2</sub>S-induced analgesia was observed in response to central administration of CTAP and MOR antisense, while κ and δ receptors were less involved. H<sub>2</sub>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 K<sub>ATP </sub>channels blocker.</p> <p>Conclusions</p> <p>This study provides pharmacological and molecular evidence that antinociception exerted by H<sub>2</sub>S in a rodent model of visceral pain is modulated by the transactivation of MOR. This observation provides support for development of new pharmacological approaches to visceral pain.</p> |
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| Item Description: | 10.1186/1744-8069-6-36 1744-8069 |