Genetic Basis for Opioid Sensitivity in Pain Treatments

Capitol Pain Institute (CPI) recently reported how the U.S. Food and Drug Administration (FDA) is addressing the worrisome rise in the misuse and addiction of opioid pain medications. Now, there is a new study out implicating a specific genetic variation the may be responsible for opioid sensitivity and how different patients will respond unequally to the same level of medications.

Opioid-based pain medications work by activating the Mu-opioid receptor primarily located in the central nervous system or peripheral nervous system. They are useful in that they help to decrease the perception of pain that the patient feels.

But opioid medications can also be highly addictive and have withdrawal symptoms if stopped abruptly. To further complicate matters, not every patient responds to these types of pain medications the same way. A subpopulation of patients is not getting the same pain relief from standard doses. The new study points out that chances are that these particular patients may possess a specific genetic variation that make them less sensitive to opioids and more prone to addiction than others..

“Some people don’t seem to respond as well, and doses need to be raised in order to have adequate pain control, but that increases the risks of side effects, including addiction,” said Priyank Kumar, PhD, an assistant professor and head of laboratory research at the Touro College of Pharmacy in New York, New York.

In the new opioid study, Dr. Kumar along with colleagues Drs. Zvi Loewy and Maureen Sullivan conducted a literature review exploring how a genetic mutation in the μ-opioid receptor (OPRM1) gene – A118G – could influence drug metabolism and addiction. Their review produced numerous insights about the implications of A118G, and these doctors suggest screening patients before receiving opioid-based pharmacotherapy.

While there are standard dosages set for different opioid medications, patients with the A118G polymorphism may not receive adequate pain relief from the standard typical dosages. It is trait that negatively could affect patient outcomes, especially post-surgery.

For example, one of the most common adverse events associated with post-surgical pain management, respiratory depression occurs in about 41% of post-op patients. The genetic variation is not a minor anomaly in patient populations, though. According to Dr. Kumar, one study in the literature review reported 64.7% of a cohort of Caucasian female patients suffering from migraine with aura had tested for the polymorphism, and another study found 85% of Caucasians had associated with the genetic variant.

Unfortunately, patients with the A118G polymorphism also display more susceptibility to addiction. Therefore, simply increasing the dosage is not an answer. However, knowing which patients have the genetic variation could be useful for making more precise, effective treatment decisions and practicing caution with long-term opioid utilization.
“Genetic testing is done routinely when treating illnesses like cancer, and many medications are designed based on this information. But for pain medications, such genetic testing is not popular,” said Dr. Kumar.

Despite the fact of increasing evidence of the clinical implications associated with the A118G polymorphism, the costs associated with genetic testing have been a prohibitive factor. We at CPI hope that as genetic testing becomes more accessible and applicable to clinical practice, our pain doctors and specialists can use the information to enhance pain management options for vulnerable patient groups thereby optimizing pain management therapies and methodologies in the years to come.

References:

Pokotylyuk I, Sullivan M, Loewy Z, Kumar P, et al. (May, 2016). Assessment of the effect of µ-opioid receptor A118G polymorphism in analgesia. Poster presented as part of the Touro College Research Day, Harlem, New York.

Hwang IC, Park JY, Myung SY, et al. OPRM1 A118G gene variant and postoperative opioid requirement: A systematic review and meta-analysis. Anesthesiology. 2014;121(4):825-834.

Overdyk FJ, Carter R, Maddox RR, et al. Continuous oximetry/capnometry monitoring reveals frequent desaturation and bradypnea during patient-controlled analgesia.Anesth Analg. 2007;105:412-418.

Voepel-Lewis T, Marinkovic A, Kostrzewa A, et al. The prevalence of and risk factors for adverse events in children receiving patient-controlled analgesia by proxy or patient-controlled analgesia after surgery. Anesth Analg. 2008;107:70-75.

Sadhasivam S, Boat A, Mahmoud M. Comparison of patient-controlled analgesia with and without dexmedetomidine following spine surgery in children. J Clin Anesth. 2009;21:493-501.

Lotsch J, Dudziak R, Freynhagen R, et al. Fatal respiratory depression after multiple intravenous morphine injections. Clin Pharmacokinet. 2006;45:1051-1060.

Brennan F, Carr DB, Cousins M. Pain management: A fundamental human right. Anesth Analg. 2007;105:205-221.

Chidambaran V, Mavi J, Esslinger H, et al. Association of OPRM1 A118G variant with risk of morphine-induced respiratory depression following spine fusion in adolescents.Pharmacogenomics J. 2015;15(3): 255-262.

Huang P, Chen C, Mague SD, et al. A common single nucleotide polymorphism A118G of the mu opioid receptor alters its N-glycosylation and protein stability. Biochem J. 2012;441:379-386.

Robinson JE, Vardy E, DiBerto JF, et al. Receptor reserve moderates mesolimbic responses to opioids in a humanized mouse model of the OPRM1 A118G polymorphism.Neuropsychopharmacology. 2015;40(11):2614-2622.

Henderson-Redmond AN, Yuill MB, Lowe TE, et al. Morphine-induced antinociception and reward in ‘humanized’ mice expressing the mu opioid receptor A118G polymorphism. Brain Res Bull. 2016;123:5-12.

Peciña M, Love T, Stohler CS, et al. Effects of the Mu opioid receptor polymorphism (OPRM1 A118G) on pain regulation, placebo effects, and associated personality trait measures. Neuropsychopharmacology. 2015;40(4):957-965.

Zhang Y, Picetti R, Butelman ER, et al. Mouse model of the OPRM1 (A118G) polymorphism: Differential heroin self-administration behavior compared with wild-type mice. Neuropsychopharmacology. 2015;40(5):1091-1100.

Song Z, Du B, Wang K, et al. Effects of OPRM1 A118G polymorphism on epidural analgesia with fentanyl during labor: A meta-analysis. Genet Test Mol Biomarkers. 2013;17(10):743-749.

Recent Posts

Share this Post