title: Genetics of pain, opioids, and opioid responsiveness.
abstract: Pain is an integral part of the defense mechanisms required for survival. Several hereditary syndromes of complete or almost complete insensitivity to pain have been identified and include channelopathy-associated pain insensitivity, of which the most likely candidate gene is the α-subunit of the voltage-gated sodium channel known as Na(v)1.7. Five hereditary sensory and autonomic neuropathy syndromes have been described. Variable pain sensitivity in the general population has been linked to common variants of the μ-opioid receptor and of the catecholamine-O-methyltransferase genes potentially leading to increased opioid tonus. Variants of the guanosine triphosphate cyclohydrolase 1/dopa-responsive dystonia gene appear to regulate nociception. Other candidate genes are the transient receptor potential cation channel, subfamily 5 member 1, gene and the melanocortin-1 receptor gene. Candidate genes for predicting opioid efficacy are drug-metabolizing enzymes and transporters-including cytochrome P450, uridine 5'-diphosphate-glucuronosyltransferases, and adenosine triphosphate-binding cassette transporters-that are involved in opioid metabolism. Most current knowledge on the genetic regulation of pain has been derived from animal models developed mainly in mice. Genomics has the potential to contribute to therapeutic advances with the promising approach of using small interfering RNA in the control of neuropathic pain. Knowledge of the genetic factors that affect opioid efficacy, metabolism, and adverse effects has the potential for personalizing both acute and chronic pain management, and for designing more useful opiate pain medications with lower adverse event profiles.
authors.affiliation: Research Centre, Centre hospitalier de l'Université de Montréal (CRCHUM)-Technopôle Angus, Montreal, Quebec, Canada. johanne.tremblay.@umontreal.ca
authors.forename: Johanne
authors.initials: J
authors.lastname: Tremblay
authors.forename: Pavel
authors.initials: P
authors.lastname: Hamet
mesh_terms: D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000818:Animals; D004195:Disease Models, Animal; D009477:Hereditary Sensory and Autonomic Neuropathies / Q000235:genetics; D006801:Humans; D062556:NAV1.7 Voltage-Gated Sodium Channel; D010146:Pain / Q000188:drug therapy* / Q000235:genetics*; D017288:Pain Threshold; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine; D015222:Sodium Channels / Q000235:genetics
chemical_list: D000701:Analgesics, Opioid; D062556:NAV1.7 Voltage-Gated Sodium Channel; C486866:SCN9A protein, human; D015222:Sodium Channels