The pharmacology of<unk> s involves the substance binding to<unk>  receptors in the nervous system and other tissues. The three known and defined receptors are mu, kappa and delta, with many other receptors reported as well. These receptors are notable for binding<unk> s and eliciting an analgesic response, thus alleviating the sensation of pain. The mu<unk>  receptor is targeted most often by<unk> s to relieve pain. Two of the most commonly used<unk>  antagonists at the mu receptor are naltrexone and naloxone. The pharmacology for<unk>  is more complicated, and is believed to involve the activation of NMDA receptors and increased excitatory peptide neurotransmitters (such as cholecystokinin). Pharmacogenomics== There is increasing evidence in support of genetics being a key factor in the development of<unk>  through its influence on both pain sensitivity and analgesic control. Current evidence indicates that the genetic influence stems from polymorphisms of the gene coding for the enzyme, Catechol-O-Methyltransferase (COMT). Its enzymatic activity varies depending on its three possible genotypes, which are seen as a single amino acid change from valine to methionine, resulting in significant variability in its activity. Degradation of the neurotransmitters, dopamine and noradrenaline, is approximately 4-fold greater when the amino acid presented is valine instead of methionine. This results in modulation of the dopaminergic and noradrenergic response at the synaptic level of neurons, which has been linked to having effects on memory function, anxiety, and pain sensitivity in comparison to individuals presenting as homozygous for valine alleles of this particular gene (COMTval158). A number of<unk> s undergo metabolism by cytochrome P450 enzymes in order to generate active metabolites. Only by generating these active metabolites can analgesic effects occur. The enzyme CYP2D6 is used to metabolize several<unk> s including codeine, methadone, hydrocodone, and tramadol. The level of expression of CYP2D6 can vary dramatically between different individuals. Individuals with low expression of CYP2D6 are designated as poor metabolizers while individuals with high expression of CYP2D6 are designated as fast metabolizers. This information is important for healthcare professionals to know as it determines the dose of<unk> s a patient will need in order to achieve the desired analgesic effect. If given the same starting dose of codeine, an ultra-rapid metabolizer will feel more pain relief due to the high expression of CYP2D6, resulting in more codeine being turned onto morphine. Poor metabolizers may feel an initial short reduction in pain followed by a quick return to baseline. Patients who are poor metabolizers should be given minimal amounts of<unk> s such as tramadol and codeine as they do not possess the necessary enzymes to turn it into it‘s active metabolite Desmetramadol. Information regarding a patient's CYP2D6 expression can be found by running a genomic test such as 23andMe. This information is also helpful to healthcare professionals so they may modify the dosing of other drugs that may have drug-drug interactions with<unk> s such as rifampin.
Opioid-induced hyperalgesia
Nociplastic pain
Hypoalgesic effect of swearing
Central pain syndrome
Psychogenic pain
Neurogenic inflammation
Neuraxial blockade
Neuropathic pain