Opioid use is widespread in the management of pain associated with acute surgical interventions as well as chronic illnesses, such as cancer and arthritis . The application of opioids, which mediate their effects via opioid-specific G-coupled protein receptors, results in significant control of pain and alleviation of its debilitating effects . However, marked variability in responsiveness to opioids amongst individuals and the accompanying complications, including overdose-associated mortality, remains a major limitation for their use. Thus, a better understanding of the factors that influence person-to-person responsiveness to opioids would allow for more appropriate and tailored dosing regimens and would reduce opioid-related morbidity and mortality.
In the study by Angst et al. , the authors examined the contribution of genetic and environmental contributions to variability in pain sensitivity and responsiveness to opioid analgesics using a twin study paradigm. The pain sensitivity of a total of 112 twin pairs were examined at baseline and following opioid infusion using heat and cold-pressor pain sensitivity testing, two well-validated pain modalities. Analysis of the pain sensitivity at baseline and following opioid infusions showed strong heritability for cold-pressor pain tolerance response. Indeed, genetic effects accounted for 49% of pain tolerance response variance at baseline, and 30% of the variance in analgesic responsiveness. Similarly, genetic effects accounted for 60% of the pain threshold response variance following analgesia in the cold-pressor pain test and 12% of the pain threshold response variance following analgesia in the heat pain test (Fig. 1). These findings indicate that inter-individual variance in responsiveness to opioid analgesics is at least in partly genetically determined.
Other more general covariates that were examined included gender, age, race, anxiety levels, depression state, sleep patterns and blood pressure. Of these, gender, age, race, and anxiety levels were found to influence inter-individual variability in pain sensitivity and responsiveness to opioids. Women showed higher sensitivity to pain than men and were less responsive to opioids. Older subjects showed significantly higher baseline pain sensitivity and had a more pronounced opioid response on cold-pressor pain than heat pain. Finally, Caucasians were significantly less sensitive to cold-pressor pain and had an enhanced opioid responsiveness to cold-pressor pain. Subjects suffering from anxiety displayed significantly increased sensitivity to cold-pressor pain. Other covariates such as depression state, sleep patterns and blood pressure did not result in any significant effects on pain sensitivity or opioid analgesia.
The study by Angst et al. shows that in addition to environmental influences, genetic factors do indeed contribute to the variance in pain sensitivity at baseline and following opioid analgesia. Follow-up studies aimed at identifying the genetic factors underlying the differential responsiveness to opioid analgesia would allow for optimized dosing and aid in providing safer, fine-tuned and personalised approaches to opioid therapy.