Overall, it is clear that the MOR is not a simple on-off switch and that the diverse means by which the receptor can be regulated may present an opportunity to refine therapeutics for the treatment of pain.
Mu opioid receptor (MOR) is involved in various brain functions, such as pain modulation, reward processing, and addictive behaviors, and mediates the main pharmacologic effects of morphine and other opioid compounds.
Accordingly, a functional μ-opioid receptor (OPRM1) polymorphism (C77G in primates, A118G in humans) affecting opioidergic signaling has been associated with separation distress and attachment behavior in nonhuman primates, and social pain sensitivity in humans.
The methylation of genes coding for the Toll-like receptor 4 (TLR4) as a major mediator of glial contributions to persistent pain or for the μ-opioid receptor (OPRM1) was analyzed and its association with the pain phenotype was compared with that conferred by global genome-wide DNA methylation assessed via quantification of the methylation in the retrotransposon LINE1.
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.
The meta-analysis results indicated that G-allele carriers (AG+GG) of the OPRM1A118G polymorphism required higher opioid doses for pain management than those with the AA homozygotes (SMD=-0.3; 95% confidence interval [CI], -0.45 to -0.15; P<0.001).
This paper aimed at assessing the efficacy and tolerability of tapentadol prolonged release (PR), a molecule with a unique mechanism of action combining μ-opioid-receptor (MOR) agonism and noradrenaline reuptake inhibition (NRI), administered to patients aged ≥80 years with chronic persistent pain.
Pain remains a global health challenge.For decades, clinicians have been primarily relying on μ-opioid receptor (MOR) agonists and nonsteroidal anti-inflammatory drugs (NSAIDs) for pain management.
Few associations replicated: morphine dose (mcg/kg) in African American children and ABCB1 rs1045642 (A allele, β = -9.30, 95% CI: -17.25 to -1.35, p = 0.02) and OPRM1rs1799971 (G allele, β = 23.19, 95% CI: 3.27-43.11, p = 0.02); KCNJ6 rs2211843 and high pain in African American subjects (T allele, OR 2.08, 95% CI: 1.17-3.71, p = 0.01) and in congruent European Caucasian pain phenotypes; and COMT rs740603 for high pain in European Caucasian subjects (A allele, OR: 0.69, 95% CI: 0.48-0.99, p = 0.046).
Thus, MOR activation efficiently alleviates severe pain, but the concomitant reward and respiratory depressant effects pose a threat; patients taking opioids potentially develop opioid addiction and high risk for overdose.
Of note, descending inhibitory pain pathways are often disrupted in chronic OA pain, and pharmacotherapies targeting those pathways - eg, those that block norepinephrine reuptake may be more appropriate for managing chronic pain than pure μ-opioid receptor (MOR) agonists.
PubMed, Cochrane library, and EMBASE databases were systematically searched up to May 5, 2018, using the keywords "OPRM1," "genetic variant," "opioid," and "pain" to identify reviews or meta-analyses on this topic.
The aim of this study was to evaluate the association between OPRM1 and ABCB1 polymorphisms on pain relief with epidural sufentanil in 69 patients after rectosigma resection for cancer.
MCC22 consists of mu opioid receptor (MOR) agonist and chemokine receptor 5 (CCR5) antagonist pharmacophores connected through a 22-atom spacer and was designed to target a putative MOR-CCR5 heteromer localized in pain processing areas.
The role of tapentadol-an analgesic molecule characterized by an innovative mechanism of action (i.e., µ-opioid receptor [MOR] agonism and inhibition of noradrenaline [NA] reuptake [NRI])-in the modulation of pain, and the most recent pharmacological evidence on this molecule (e.g., the µ-load concept) are also presented and commented upon.<b>
Together, our data reveal a TRPV1-mediated signaling pathway that serves as an endogenous pain-resolution mechanism by promoting the nuclear translocation of β-arrestin2 to minimize MOR desensitization.
G<sub>i</sub> -protein-biased agonists with minimal β-arrestin recruitment represent opportunities to overcome the serious adverse effects of human mu opioid receptor (μ-OR) agonists and developing alternative and safe treatments for pain.
To analyze in a population from Argentina the variation of three genes involved in the control of pain pathways-two genes that code for opioid receptors (OPRM1 and OPRK1) and COMT, which codes for an important enzyme in the control of neurotransmission-and to evaluate the associations of these genes with oral pain and the need for analgesics in the population under study.