Genetic basis of pain variability: recent advances

Abstract

An estimated 15–50% of the population experiences pain at any given time, at great personal and societal cost. Pain is the most common reason patients seek medical attention, and there is a high degree of individual variability in reporting the incidence and severity of symptoms. Research suggests that pain sensitivity and risk for chronic pain are complex heritable traits of polygenic origin. Animal studies and candidate gene testing in humans have provided some progress in understanding the heritability of pain, but the application of the genome-wide association methodology offers a new tool for further elucidating the genetic contributions to normal pain responding and pain in clinical populations. Although the determination of the genetics of pain is still in its infancy, it is clear that a number of genes play a critical role in determining pain sensitivity or susceptibility to chronic pain. In the present review, the authors provide an update of the most recent findings that associate genetic variation with variability in pain and an overview of the candidate genes with the highest translational potential.

Preventive Analgesia and Novel Strategies for the Prevention of Chronic Post-Surgical Pain

“…This individual variability suggests that there are several factors which contribute to the development of CPSP (both genetic and environmental). Recent reviews in pain genetics estimate that chronic pain heritability ranges from 30 to 70 % [78]. Presently it is not possible to ascertain the extent to which individual genetic factors contribute to a person's propensity to develop chronic postsurgical pain or their response to therapy [79].…”

Genetics of chronic post-surgical pain: a crucial step toward personal pain medicine

“…These studies indicate that chronic pain has heritability ranging from 30-70% (median* 45%). 19,20 Heritability estimates attempt to assess the relative contributions of genetic and non-genetic factors to the total phenotypic variation in a population. 21 While mutation in a single gene is causal for the disorder in monogenic diseases (by definition), complex disorders such as chronic pain do not have a single genetic cause but are the result of the interaction of many genes (each having a small effect on the trait variance) with several environmental factors.…”

Prevention of chronic pain after surgery: new insights for future research and patient care

“…14,27 In this context, a genetic disposition for being a high-risk pain responder and at risk for persistent pain is currently receiving much attention. 28,29 At this time, various other techniques with preoperative nociceptive stimulation to predict high-pain responders have been described 30 and may be of future use to allocate high-risk pain patients to more intensive postoperative pain therapy. Thus, while assessment, identification, and occasional stratification of these preoperative factors are critical for well-designed, observational, and interventional studies, it is also important for clinicians to monitor higher-risk patients much more closely in the postoperative period.…”

“…14,27 Dans un tel contexte, l'hypothèse qu'il existe une prédisposition génétique à courir un risque élevé de réagir à la douleur et un risque de souffrir de douleur persistante reçoit à l'heure actuelle beaucoup d'attention de la part de la communauté scientifique. 28,29 Plusieurs autres techniques impliquant la stimulation nociceptive préopératoire pour identifier les personnes répondant fortement à la douleur ont déjà été décrites; 30 ces techniques pourraient s'avérer utiles à l'avenir pour garantir que les patients courant un risque plus élevé de souffrir de douleur reçoivent un traitement postopératoire de la douleur plus intensif. Ainsi, bien que l'évaluation, l'identification et la stratification occasionnelle de ces facteurs préopératoires soient cruciales à la réalisation d'études interventionnelles observationnelles bien conçues, il est également important que les cliniciens surveillent plus assidûment les patients à plus haut risque au cours de la période postopératoire.…”