"Since hypnotizability is a stable cognitive trait with a genetic basis, our goal was to create a molecular diagnostic tool for objectively identifying individuals who would benefit from hypnosis by determining 'treatability' at the point-of-care," explained co-lead investigator Dana L. Cortade, a recently graduated PhD in Materials Science and Engineering, School of Engineering, Stanford University, Stanford, CA, USA. "The advancement of nonpharmacological adjuvant treatments for pain is of the utmost importance in light of the opioid epidemic."

Prior research established that the genetic basis for hypnotizability includes four specific single-nucleotide polymorphisms (SNPs), or genetic variations, found in the catechol-o-methyltransferase(COMT)gene for an enzyme in the brain that is responsible for dopamine metabolism in the prefrontal cortex. Although SNPs can contain valuable information on disease risk and treatment response, widespread use in clinical practice is limited because of the complexities, costs, and time delays involved in sending samples to laboratories for testing.

The investigators developed a SNP genotyping assay on a giant magnetoresistive (GMR) biosensor array to detect the optimal combination of theCOMTSNPs in patient DNA samples. GMR biosensor arrays are reliable, cheaper, sensitive, and can be easily deployed in point-of-care settings using saliva or blood samples.

The study investigated the association betweenCOMTdiplotypes and hypnotizability using a clinical hypnotizability scale called the Hypnotic Induction Profile (HIP) in individuals who had participated in one of the three previous clinical trials in which an HIP was administered. An additional exploratory study of the association between perioperative pain,COMTgenotypes, and HIP scores was conducted with the patients in the third cohort, who had undergone total knee arthroplasty (TKA). DNA was extracted from blood samples previously collected in the first cohort, and saliva samples were collected by mail from participants in the other two trials. Participants were considered treatable by hypnosis if they had HIP scores of 3 or higher on a scale of zero to 10.

For participants identified with the optimalCOMTdiplotypes by the GMR biosensor array, 89.5% scored highly on the HIP, which identified 40.5% of the treatable population. The optimalCOMTgroup mean HIP score was significantly higher than that in the suboptimalCOMTgroup. Interestingly, further analysis revealed that the difference was observed only in women.

"Although we had expected some difference in effect between females and males, the association between hypnotizability andCOMTgenotypes was strongest in the females in the cohort," said co-lead investigator Jessie Markovits, MD, Department of Internal Medicine, Stanford School of Medicine, Stanford, CA, USA. "The difference may be due to lower numbers of males in the cohort, or becauseCOMTis known to have interactions with estrogen and to differ in activity by sex. Additional gene targets includingCOMT, with stratification by sex, could be the focus of future study."

In the exploratory analysis of the relationship betweenCOMTgenotypes and pain after TKA surgery, the same optimalCOMTindividuals had significantly higher postoperative pain scores than the suboptimal group, indicating a greater need for treatment. "This supports the body of evidence thatCOMTgenotypes impact pain, and it is also known thatCOMTgenotypes affect opioid use after surgery. Pain researchers can use this technology to correlate genetic predisposition to pain sensitivity and opioid use with response to an evidence-based, alternative remedy: hypnosis," Dr. Cortade said.

COMT单核苷酸多态性一致格本身并不是一个完整的生物标志物fying all individuals who will score highly on a hypnotizability scale and experience high pain sensitivity. The GMR sensor nanoarray can accommodate up to 80 SNPs, and it is possible that other SNPs, such as those for dopamine receptors, are needed to further stratify individuals.

The investigators observe that this study highlights the utility and potential of the evolving applications of precision medicine. "It is a step towards enabling researchers and healthcare professionals to identify a subset of patients who are most likely to benefit from hypnotic analgesia," Dr. Markovits said. "Precision medicine has made great strides in identifying differences in drug metabolism that can impact medication decisions for perioperative pain. We hope to provide similar precision in offering hypnosis as an effective, non-pharmacological treatment that can improve patient comfort while reducing opioid use."