Personalizing Pain Medicine: The Future of Treatment
Low concentrations of metabolites evoked fatigue sensations and high concentrations evoked muscle ache.
AUSTIN, Texas — Understanding your patient's genetic makeup may provide important clues about how best to treat them, according to a speaker at the American Pain Society Meeting 2016. 1
Alan R. Light, PhD, of the Departments of Anesthesiology and Neurobiology and Anatomy, University of Utah School of Medicine, explained that there are important clues to how a patient may process muscle ache and fatigue within their RNA sequence.
Discovering how a patient will respond to muscle ache and fatigue is important he said, because both muscle ache and fatigue great influence people's behaviors.
“Memories of ache reduce the motivation to repeat the event,” he said, adding that fatigue can have similar effects on patients. “If sense of fatigue is too strong, it can be very aversive, leading to suffering and the inability to go through the motion that is life.”
Discussing the signals of muscle ache and fatigue, Dr Light noted that research by Pollak et al concluded that “low concentrations of metabolites evoked fatigue sensations and high concentrations evoked muscle ache.” 2
Explaining how this process occurs, Dr Light noted data from his research that looked at those molecules that are involved in increases in metabolites. His group pipetted neurons and put them in a lysis buffer, and from that data, the group concluded that there are two populations of muscle innervating dorsal root ganglian neurons, specifically, those that respond best to metabolites at painful levels and at nonpainful levels.
“QPCR indicated that nearly all of the genes were were interested in were expressed more in neurons than innervated skeletal muscle,” Dr Light noted, providing a possible opportunity for therapeutic intervention, he said. He noted that ASICs are all important for muscle sensory neurons, as well as OPRM1, TRPV1, TRPA1 and 3P2X receptors.
He said their group also used RNAseq to “verify the receptors we had predicted and determined what we missed,” which revealed that 18 of 19 of their study patients had at least one mitochondrial gene variant. Learning this information is key, he said, because knowing what genetic variants exist on a particular patient can help guide treatment decisions.
"The technology is already there, the biggest problem is cost, and people who know what they are doing to run it," he said.
1. Light AR. Big data on nociceptive afferants. Presented at: APS 2016. May 11-14, 2016, Austin, Tx.
2. Pollak KA, Swenson JD, Vanhaitsma TA, et al. Exogenously applied muscle metabolites synergistically evoke sensations of muscle fatigre and pain in human subjects. Exp Physiol. 2014;368-380