The genetic mediation of individual differences in sensitivity to pain and its inhibition

Abstract

The underlying bases of the considerable interindividual variability in pain-related traits are starting to be revealed. Although the relative importance of genes versus experience in human pain perception remains unclear, rodent populations display large and heritable differences in both nociceptive and analgesic sensitivity. The identification and characterization of particularly divergent populations provides a powerful initial step in the genetic analysis of pain, because these models can be exploited to identify genes contributing to the behavior-level variability. Ultimately, DNA sequence differences representing the differential alleles at pain-relevant genes can be identified. Thus, by using a combination of ''top-down'' and ''bottom-up'' strategies, we are now able to genetically dissect even complex biological traits like pain. The present review summarizes the current progress toward these ends in both humans and rodents.

Variation and homogeneity in affective responses to physical activity of varying intensities: An alternative perspective on dose – response based on evolutionary considerations

“…According to Tooby and Cosmides (1990b), ''people display more diversity in their preferences for hat color or in their beliefs about gods and spirits than in their desire to continue breathing, their attraction to sex, or their desire to avoid pain'' (p. 58). Nevertheless, although there is a general ''desire to avoid pain'', there is also considerable heritable variation in pain sensitivity and tolerance (Mogil, 1999), as well as in the preferred level of sensory stimulation (Eysenck, 1983;Fulker, Eysenck, & Zuckerman, 1980). Presumably, this variability exists because these traits are, ultimately, adaptively neutral, involving a trade-off between benefits and risks.…”

Exploring joint effects of genes and the clinical efficacy of morphine for cancer pain: OPRM1 and COMT gene

“…We also recognize that the complexity of morphine pharmacology suggests that the variability in opioid pain treatment is associated with genetic variation in several genes (Mogil 1999 Despite major improvement in pain control over the last 15 years, cancer-related pain continues to be a significant public health concern. Morphine is recommended as a first line strong opioid (World Health Organisation Geneva 1996).…”

Spinal G-Protein-Gated K+Channels Formed by GIRK1 and GIRK2 Subunits Modulate Thermal Nociception and Contribute to Morphine Analgesia

“…Frequent criticisms of constitutive gene ablation studies relate to the myriad potential compensatory processes that could be triggered by the absence of the targeted gene throughout development, as well as subtle interactions that could occur between the targeted gene, genetic background, and environment (Mogil et al, 1996;Mogil, 1999). We attempted to address these concerns using multiple approaches.…”