engleski

Heritability analysis suggests comparable genetic component of mechanical pain threshold and tolerance

Genetic basis of pain sensation became one of the hot topics in pain medicine over the past several years. Although numerous studies have suggested the existence of the genetic component of pain threshold, majority of these findings were based on a candidate-gene approach and remained un-replicated, and thus of limited importance (1). Commonly used approach to investigate genetic basis of any trait is to initially estimate heritability, which is defined as the proportion of the total variance of the measured trait attributable to genes. We performed a heritability analysis of the mechanical pain threshold and tolerance in a large-scale pedigree, based on the isolated population of the island of Vis in Croatia, within 10, 001 Dalmatians project (2). A total of 349 subjects were involved in the measurement of mechanical pain threshold and pain tolerance using Algometer Wagner ForceOne. After initial training measurement, subjects were exposed to the actual pain threshold measurement. Three consecutive pain threshold measurements on the dorsal side of the middle phalange of the index finger (on both hands) were performed by a single trained measurer. Additionally, we performed two consecutive measurements of pain tolerance on the same site of both hands. Mixed model analysis was performed using Sequential Oligogenic Linkage Analysis Routines – SOLAR (3), with age and gender as the predictor variables. The results indicated intermediate level of heritability of pain threshold (0.508 for right hand and 0.362 for left hand) and pain tolerance (0.542 for right hand and 0.307 for left hand, notably, the last heritability estimate was not significant ; Table 1). A strong gender and age effects were recorded in all models, with the exception of age in the pain threshold models (Table 1). These results suggest that gene mapping efforts are likely to have similar success both in pain threshold and pain tolerance, despite some previous suggestions that pain threshold is more a physiological function, while tolerance is influenced by stronger modifying effects of different environmental and psychological confounders (4). Furthermore, it should be noted that we detected difference in handedness - the heritability for pain tolerance in left hand was insignificant, with very large standard errors. This could arise from the overall small sample size or it could be pointing to differential mechanisms of pain tolerance in left vs. right, that is dominant, vs. non-dominant hand, which was implied before (5). Regardless of these results, high heritability does not warrant productive gene mapping. Heritability of height was commonly reported as one of the highest ones, generally in the range of 0.92-0.97. However, only creation of a mega-consortium of studies, which consisted of over 180, 000 measured subjects and used genome-wide approach, surpassed previous nearly futile efforts and yielded 180 loci involved in determination of the adult height, and showed a highly polygenic genetic architecture of height (6). If the same is applicable to pain, then we might be expecting a rather complex and lengthy search for genetic architecture of pain. However, the use of hypothesis-free approach, such as genome-wide association study, promises wider and deeper understanding of pain sensation, which is interesting not only for better understanding, but also for the development of new approaches to pain diagnosis and treatment.

heritability; pain

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