Genetics and Pain

Genetics and Pain

by Keith Candiotti, MD

Expert authors received compensation from Janssen Pharmaceuticals, Inc. for their contributions to PrescribeResponsibly.com

Anyone who has ever cared for patients who are injured or in pain has noted the marked degree of variability in pain responses from patient to patient. Large differences in reported pain levels are ubiquitous, with this effect being noted for both consistent tissue injuries (eg, surgery) as well as less defined systemic diseases or unknown causes (eg, fibromyalgia).48 In medicine, healthcare professionals traditionally are taught to treat all patients in the same manner. This approach may, in fact, be harmful to many. Differences in pain tolerance and response to pain medications are partially, but significantly, linked to a patient's genetic makeup. Without considering these factors, it is easy to either undertreat or overtreat a patient. Currently, it is unusual for a physician to know anything about a patient's genetic makeup. A patient's medical and family history and ethnicity, however, may often hold useful clues concerning this area.

Genes and Pain Response

The pain response is complex. The final resulting pain experience occurs as a product of many factors, including genetic composition, prior experience, physiological status, appraisals and expectations, mood, behavioral repertoire of pain-coping skills, and sociocultural background.49 Which factors, and to what extent they have an impact on the final behavior of a patient, is an area of considerable controversy.

Many genes and their polymorphic variants appear to affect the pain response. Only a few of them, however, have been studied, and some of the trials have produced conflicting results.50 Some genes that have been shown to have a statistically significant pharmacogenetic modulation on the therapeutic effects of opioid analgesics include µ-opioid receptor (OPRM1); catechol-O-methyl transferase (COMT); melanocortin-1 receptor (MC1R); cytochrome P450 2D6 (CYP2D6); ATP, binding cassette, B1 (ABCB1); and interleukin receptor antagonist.50 The degree that each of these genes affects the pain response is still unclear, but it is apparent that they can play a significant role.

Advances and the Future of Pain Genomics

While many factors produce the pain phenotype, the role of heritability is apparently more significant than previously thought. As research progresses and more data become available, the degree of genetic contribution will no doubt become clearer. A decade ago, the field of pain genomics was basically unknown, but today the area is rapidly advancing with new information and data appearing in the literature on a regular basis. As our understanding of the heritability of the pain phenotype increases, new treatment options may become apparent as well.

References Used in the Section:

  • 48 Nielsen CS, Staud R, Price DD. Individual Differences in Pain Sensitivity: Measurement, Causation, and Consequences. The Journal of Pain. 2009; 10(3):231-237.
  • 49 Edwards RR. Genetic Predictors of Acute and Chronic Pain. Current Rheumatology Reports. 2006; 8:411-417.
  • 50 Lötsch J, Geisslinger G. Current evidence for a genetic modulation of the response to analgesics. Pain. 2006; 121:1-5.