Endomorphin-1 and Endomorphin-2: Involvement of Endogenous μ-Opioid Receptor Ligands in Analgesia, Antinociceptive Tolerance, Antianalgesia, and Hyperalgesia

Publication date: October 2014 Source:Journal of Experimental & Clinical Medicine, Volume 6, Issue 5 Author(s): Leon F. Tseng Endomorphin-1 (EM-1) and endomorphin-2 (EM-2) are endogenous ligands for μ-opioid receptors. Both EM-1 and EM-2, given supraspinally or spinally, produce potent antinociception (analgesia) in mice and rats, measured by the thermal tail-flick response. The antinociception produced by either EM-1 or EM-2 is mediated by the stimulation of μ-opioid receptors, but not by δ- or κ-opioid receptors. EM-1 or EM-2 given supraspinally stimulates primarily μ-opioid receptors and subsequently releases spinipetal noradrenaline and serotonin, acting on α2-adrenoceptors and serotonin receptors in the spinal cord for producing antinociception. However, the antinociception produced by EM-2, but not by EM-1, also contains an additional component, which is mediated by the release of dynorphin A1–17 and Met-enkephalin acting on κ-opioid receptors and δ2-receptors, respectively, in the spinal cord for producing antinociception. Pretreatment with EM-1 or EM-2, given supraspinally or spinally, attenuates the antinociception (antinociceptive tolerance) produced by EM-1 or EM-2, respectively. Pretreatment with EM-2 attenuates the antinociception produced by EM-1; however, pretreatment with EM-1 does not attenuate the antinociception produced by EM-2 (asymmetric cross-tolerance). The antinociception produced by (–)-morphine given into the ventral periaqu...
Source: Journal of Experimental and Clinical Medicine - Category: Journals (General) Source Type: research