The μ opiate receptor is responsible for descending pain inhibition originating in the periaqueductal gray region of the rat brain

Abstract

Opiate agonists exhibiting selectivity for μ, κ, σ and δ opiate receptors were microinjected into the periaqueductal gray region (PAG) of the brain of rats to determine the receptor subtype(s) associated with the initiation of descending pain inhibition. The spinally organized, heat nociceptive tail-flick reflex was used to detect analgesia. Only morphine (μ) and [D-Ala 2, D-Leu 5]enkephalin (DADLE) ( δ> μ) produced analgesia. However, both drugs appeared to be acting through the μ (morphine) receptor, since: (1) the action of DADLE was not inhibited by δ receptor antagonists, (2) a more highly selective δ agonist [D-Pen 2, D-Pen 5]enkephalin was ineffective and (3) agonists selective at other non-μ receptor sites (ethylketocyclazocine and U50,488H for κ; n-allylnormetazocine for σ) were also ineffective. It appeared that DADLE might be acting as a partial agonist at the morphine receptor in the PAG. The peptide was an agonist with low efficacy, and when a maximally effective dose of the peptide was administered simultaneously with morphine antagonism was observed. Ethylketocyclazocine and n-allynormetazocine were also found to antagonize morphine, an observation that is consistent with the suggestion that they may act as μ receptor antagonists in addition to their agonistic action at κ and σ receptors, respectively. Thus, μ receptors appear to be responsible for the spinopetal analgesia from the PAG of the rat.