title: The role of genomic oxidative-reductive balance as predictor of complex regional pain syndrome development: a novel theory.
abstract: The aftermath of sequencing the human genome has birthed many efforts to utilize an individual's genetic information in order to tailor optimal treatment strategies - so-called personalized medicine. An individual's genetic information may eventually help diagnosis and treatment, as well selecting optimal pharmacologic agents based partly on how well they reach their target, how well they will bind to and produce an effect at their targets, how well they will be metabolized, and the profile of their adverse effects. It also appears that clinicians may be able to utilize an individual's genetic information to ascertain a subject's risk or susceptibility of developing a particular medical condition. Although, this has not been widely utilized in pain medicine at this point, the future may revolutionize the role of genetic information in the evaluation and management of various pain conditions. One reason for variations in therapeutic outcomes from different pharmacologic pain treatments is the different genetic disposition of patient to develop pain or to respond to analgesics. The patient's phenotype may represent a conglomerate of several different genetic variants concomitantly present in an individual. Genetic variants may modulate the risk of developing a painful condition, or may modulate the perception of pain (e.g. OPRM1 or GCH1 variants conferring modest "protection" from pain by increasing the tone of the endogenous opioid system or decreasing nitric oxide formation). Other genetic polymorphisms may alter pharmacokinetic mechanisms (e.g. CYP2D6 related prodrug activation of codeine to morphine), alter pharmacodynamic mechanisms (e.g. opioid receptor mutations), or alter other analgesic effects (e.g. diminished euphoric effects from opioids potentially due to DRD2 polymorphisms decreasing the functioning of the dopaminergic reward system). This article theorizes that genetic alterations including functional polymorphisms of Nrf2 (a master regulator of the transcription of multiple antioxidants) may render certain subjects more or less susceptible to developing complex regional pain syndrome after surgery or trauma. If this hypothesis is correct, knowing this information may translate into significant and "far-reaching" effects on clinical decision-making surrounding the management of pain in patients who may be more susceptible to develop complex regional pain syndrome. Furthermore, it could lead to the development of novel prevention or intervention strategies, in efforts to prevent, abort, or ameliorate the development of and/or effectively treat complex regional pain syndrome.
authors.affiliation: Albany Medical College, Department of Anesthesiology, Albany, NY 12208, USA. smithh@mail.amc.edu
authors.forename: Howard S
authors.initials: HS
authors.lastname: Smith
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D020918:Complex Regional Pain Syndromes / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000235:genetics* / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human