Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016053 (fibromyalgia)
 4,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Morphine is an analgesic drug used to treat acute and chronic pain. Obesity is frequently associated with pain of various origins (e.g. arthritis, fibromyalgia, cancer), which increases the need for analgesic drugs. Obesity changes drug pharmacokinetics, and for certain drugs, specific modalities of prescription have been proposed for obese patients. However, scant data are available regarding the pharmacokinetics and pharmacodynamics of morphine in obesity. Prescription of morphine depends on pain relief but the occurrence of respiratory adverse effects correlates with obesity, and is not currently taken into account. Variations in the volume of distribution, elimination half-life and oral clearance of morphine, as well as recent advances in the respective roles of drug-metabolizing enzymes, catechol-O-methyltransferase and the mu opioid receptor in morphine pharmacokinetics and pharmacodynamics, may contribute to differences between obese and non-obese patients. In addition, drug-drug interactions may alter the disposition of morphine and its glucuronide metabolites, which may either increase the risk of adverse effects or reduce drug efficacy.
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PMID:Pharmacology of morphine in obese patients: clinical implications. 1974 86

ProSAAS is one of the most widely expressed proteins throughout the brain and was recently found to be upregulated in chronic fibromyalgia patients. BigLEN is a neuropeptide that is derived from ProSAAS and was recently discovered to be the endogenous ligand for the orphan G protein-coupled receptor GPR171. Although BigLEN-GPR171 has been found to play a role in feeding and anxiety behaviors, it has not yet been explored in pain and opioid modulation. The purpose of this study was to evaluate this novel neuropeptide-receptor system in opioid-induced antinociception. We found that GPR171 is expressed in GABAergic neurons within the periaqueductal gray, which is a key brain area involved in pain modulation and opioid functions. We also found that, although the GPR171 agonist and antagonist do not have nociceptive effects on their own, they oppositely regulate morphine-induced antinociception with the agonist enhancing and antagonist reducing antinociception. Lastly, we showed that the GPR171 antagonist or receptor knockdown decreases signaling by the mu-opioid receptor, but not the delta-opioid receptor. Taken together, these results suggest that antagonism of the GPR171 receptor reduces mu opioid receptor signaling and morphine-induced antinociception, whereas the GPR171 agonist enhances morphine antinociception, suggesting that GPR171 may be a novel target toward the development of pain therapeutics. SIGNIFICANCE STATEMENT: GPR171 is a recently deorphanized receptor that is expressed within the periaqueductal gray and can regulate mu opioid receptor signaling and antinociception. This research may contribute to the development of new therapeutics to treat pain.
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PMID:Opioid-Induced Signaling and Antinociception Are Modulated by the Recently Deorphanized Receptor, GPR171. 3130 96