The present work aimed to investigate the effects of acute sucrose treatment on the perception of painful stimuli. Specifically, we sought to determine the involvement of the endogenous opioid peptide-mediated system as well as the role of the μ(1)-opioid receptor in antinociception organisation induced by acute sucrose intake. Nociception was assessed with the tail-flick test in rats (75, 150 ...

BACKGROUND AND PURPOSE Opioids, such as morphine, are the most effective treatment for pain but their efficacy is diminished with the development of tolerance following repeated administration. Recently, we found that morphine activated ERK in opioid-tolerant but not in naïve rats, suggesting that morphine activation of μ-opioid receptors is altered following repeated morphine administration. H...

Sustained administration of opioid antagonists to rodents results in an enhanced antinociceptive response to agonists. We investigated the changes in spinal μ-opioid receptor signalling underlying this phenomenon. Rats received naltrexone (120 μg/h; 7 days) via osmotic minipumps. The antinociceptive response to the μ-agonist sufentanil was tested 24 h after naltrexone withdrawal. In spinal cord...

Blood oxygen level dependent (BOLD) imaging in awake mice was used to identify differences in brain activity between wild-type, and Mu (μ) opioid receptor knock-outs (MuKO) in response to oxycodone (OXY). Using a segmented, annotated MRI mouse atlas and computational analysis, patterns of integrated positive and negative BOLD activity were identified across 122 brain areas. The pattern of posit...

We evaluated in vivo the μ-opioid system during spontaneous episodic migraine headaches. Seven patients were scanned at different phases of their migraine using Positron Emission Tomography with the selective μ-opioid receptor (μOR) radiotracer [11C]carfentanil. In the ictal phase, there was μOR activation in the medial prefrontal cortex, which was strongly associated with the μOR availability ...

Pain-related issues represent the most common reason for which people seek health care. 1 Opioids, such as morphine, are the most commonly prescribed class of drugs for treating moderate to severe pain. Morphine is a μopioid, δ-opioid and κ-opioid receptor agonist. Whereas, butorphanol is a synthetic opioid analgesic exhibiting partial agonist and antagonist activity at the μ-opioid receptor as...

Endomorphins (endomorphin-1, H-Tyr-Pro-Trp-Phe-NH2, endomorphin-2, Tyr-Pro-Phe-Phe-NH2) are potent and selective μ-opioid receptor agonists. In order to improve the affinity and chemical stability of endomorphins, we have designed, synthesized, and characterized novel analogs with unnatural (2′, 6′-dimethyltyrosine, Dmt) and/or β-alicyclic amino acids (ACPC and ACHC). Radioligand binding assay ...

AIMS It is considered that a long-acting therapy would be advantageous in the treatment of addiction. In a search for novel buprenorphine analogues, thienorphine was demonstrated to be an extremely long-acting orally active partial opioid agonist. This study explored the mechanisms underlying the long-lasting effects of thienorphine. METHODS The binding kinetics of [(3) H]thienorphine were me...

Although μ-opioids have been reported to interact favorably with imidazoline I2 receptor (I2R) ligands in animal models of chronic pain, the dependence on the μ-opioid receptor ligand efficacy on these interactions had not been previously investigated. This study systematically examined the interactions between the selective I2 receptor ligand 2-(2-benzofuranyl)-2-imidazoline hydrochloride (2-B...