Sugar solution analgesia: the effects of glucose on expressed mu opioid receptors

Glucose or sucrose solutions administered orally provide effective analgesia for procedural pain in neonates. Because analgesia with sugar solutions can be decreased by opioid receptor antagonists, we tested the hypothesis that glucose directly activates opioid receptors. Mu opioid receptors (MOR-1) were expressed in Xenopus oocytes, a well recognized expression system, and glucose was tested for possible agonist, antagonist, and modulatory effects on the receptor. In control experiments, 10 nM of Tyr-D-Ala-Gly-Me-Phe-Gly-ol (DAMGO), a synthetic enkephalin and specific mu agonist, activated the MOR-1, whereas 20 mM of glucose had no effect. In addition, glucose had no effect on the activation of the mu receptor by DAMGO. Finally, glucose did not modulate acute receptor desensitization induced by DAMGO. We conclude that glucose does not directly interact with MOR-1 in an in vitro expression system and that the purported interaction between glucose and the opioid system may be an indirect one, involving release of endogenous opioids.