Resume: A newly developed molecular diagnostic test is able to identify people who are most likely to benefit from hypnosis to help manage postoperative pain. This subset of highly hypnotizable people is also more likely to have higher levels of postoperative pain.
Hypnosis is an effective treatment for pain for many people, but it can be challenging to determine which patients will benefit most from it. Hypnotizability testing requires special training and personal evaluation that is rarely available in the clinical setting.
Now researchers have developed a rapid, point-of-care molecular diagnostic test that identifies a subset of individuals most likely to benefit from hypnosis interventions for pain management.
Their study, in The journal of molecular diagnostics also found that a subgroup of highly hypnotizable individuals are more likely to have high levels of postoperative pain.
“Because hypnotizability is a stable cognitive trait with a genetic basis, our goal was to create a molecular diagnostic tool for objectively identifying individuals who could benefit from hypnosis by determining ‘treatability’ at the point of care, co-principal investigator explains. Dana L. Cortade, a recent PhD graduate in Materials Science and Engineering, School of Engineering, Stanford University, Stanford, CA, USA.
“The advancement of nonpharmacological adjuvant treatments for pain is of paramount importance in the face of the opioid epidemic.”
Prior research has shown that the genetic basis for hypnotizability involves four specific single-nucleotide polymorphisms (SNPs) or genetic variations found in the catechol-o-methyltransferase (COMT) gene for an enzyme in the brain responsible for dopamine metabolism in the prefrontal cortex.
While SNPs can provide valuable information about disease risk and treatment response, widespread use in clinical practice is limited due to the complexity, cost, and time delays associated with sending samples to laboratories for testing.
The researchers developed an SNP genotyping test on a giant magnetoresistive (GMR) biosensor array to determine the optimal combination of the COMT SNPs in patient DNA samples. GMR biosensor arrays are reliable, less expensive, sensitive and can be easily deployed in point-of-care environments using saliva or blood samples.
The study examined the association between COMT diplotypes and hypnotizability using a clinical hypnotizability scale called the Hypnotic Induction Profile (HIP) in subjects who had participated in one of three previous clinical trials in which a HIP was administered.
An additional exploratory study of the association between perioperative pain, COMT genotypes and HIP scores were performed 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 studies. Participants were considered treatable with hypnosis if they had HIP scores of 3 or higher on a scale of zero to 10.
For participants identified with the optimal COMT diplotypes by the GMR biosensor array scored 89.5% high on the HIP, which identified 40.5% of the treatable population. The optimal COMT group mean HIP score was significantly higher than that in the suboptimal group COMT group. Interestingly, further analysis revealed that the difference was only seen in women.
“While we expected some difference in effect between women and men, the association between hypnotizability and COMT genotypes was strongest among the females in the cohort,” said co-principal investigator Jessie Markovits, MD, Department of Internal Medicine, Stanford School of Medicine, Stanford, CA, USA.
“The difference may be due to a lower number of men in the cohort, or because COMT is known to have interactions with estrogen and to vary in activity by gender. Additional gene targets, including COMTwith stratification by gender, could be the focus of future research.”
In the exploratory analysis of the relationship between COMT genotypes and pain after TKA surgery, the same optimal COMT individuals had significantly higher postoperative pain scores than the suboptimal group, indicating a greater need for treatment.
“This supports the amount of evidence that COMT genotypes affect pain, and it is well known COMT genotypes influence 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,” said Dr. Cortade.
COMT SNPs alone are not a complete biomarker for identifying all individuals who score high on a hypnotizability scale and experience high pain sensitivity. The GMR sensor’s 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 researchers note that this study highlights the usefulness and potential of the evolving applications of precision medicine.
“It’s a step towards enabling researchers and healthcare professionals to identify a subgroup of patients who will benefit most from hypnotic analgesia,” said Dr. Markovits.
“Precision medicine has made great strides in identifying differences in drug metabolism that may influence 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.”
About this news about pain, hypnosis and neurotech research
Author: Eileen Leahy
Contact: Eileen Leahy-Elsevier
Image: The image is in the public domain
Original research: Open access.
“Point-of-Care Testing of Enzyme Polymorphisms for Predicting Hypnotizability and Postoperative Pain” by Dana Cortade et al. Journal of Molecular Diagnostics
Point-of-Care Testing of Enzyme Polymorphisms for Predicting Hypnotizability and Postoperative Pain
Hypnotizability is a stable property that moderates the benefit of hypnosis for the treatment of pain, but the limited availability of hypnotizability tests precludes widespread use of hypnosis. Inexpensive genotyping of four single-nucleotide polymorphisms in the catechol-o-methyltransferase (COMT) gene was performed using giant magnetoresistive biosensors to determine whether hypnotizable individuals can be identified for targeted hypnosis referrals.
For individuals with the suggested optimal COMT diplotypes scored 89.5% high on the Hypnotic Induction Profile (odds ratio, 6.12; 95% CI, 1.26–28.75), which identified 40.5% of the treatable population.
Mean hypnotizability scores of the optimal group were significantly higher than those of the overall population (P = 0.015; effect size = 0.60), an effect that was present in women (P = 0.0015; effect size = 0.83), but not in men (P = 0.28).
In an exploratory cohort, optimal individuals also reported significantly higher postoperative pain scores (P = 0.00030; effect size = 1.93), indicating a greater need for treatment.