Abstract
Millions of Americans experience pain daily. In 2017, opioid overdose claimed 64,000 lives increasing to 84,000 lives in 2020, resulting in a decrease in national life expectancy. Chronic opioid use results in dependency, drug tolerance, neuroadaptation, hyperalgesia, potential addictive behaviors, or Reward Deficiency Syndrome (RDS) caused by a hypodopaminergia. Evaluation of pain clinic patients with the Genetic Addiction Risk Score (GARS) test and the Addiction Severity Index (ASI- Media Version V) revealed that GARS scores equal to or greater than 4 and 7 alleles significantly predicted drug and alcohol severity, respectively. We utilized RT-PCR for SNP genotyping and multiplex PCR/capillary electrophoresis for fragment analysis of the role of eleven alleles in a ten-reward gene panel, reflecting the activity of brain reward circuitry in 121 chronic opioid users. The study consisted of 55 males and 66 females averaging ages 54 and 53 years of age, respectively. The patients included Caucasians, African Americans, Hispanics, and Asians. Inclusion criteria mandated that the Morphine Milligram Equivalent (MME) was 30–600 mg/day (males) and 20 to 180 mg/day (females) for treatment of chronic pain over 12 months. Ninety-six percent carried four or more risk alleles, and 73% carried seven or more risk alleles, suggesting a high predictive risk for opioid and alcohol dependence, respectively. These data indicate that chronic, legally prescribed opioid users attending a pain clinic possess high genetic risk for drug and alcohol addiction. Early identification of genetic risk, using the GARS test upon entry to treatment, may prevent iatrogenic induced opioid dependence.
Highlights
Non-cancerous pain treatment is challenging for primary care medicine
While the DRD1 at 88% ranked number 1 in terms of frequency, and the lowest risk allele was the DAT1 at 1%, we found the following rank order for the tested variants: DRD1> monoamine oxidase A (MAOA)> COMT (4680)> SLC6A4/ HTTLPR > DRD4> GABRB3> DRD3> DRD2> DRD4> OPRM1 > and DAT1
The finding that 96% of these severe, chronic opioiddependent patients showed a high Genetic Addiction Risk Score (GARS) in this cohort may, at first glance, may be somewhat surprising, but it does support the hypothesis that concomitant chronic opioid users would have a high GARS score
Summary
Non-cancerous pain treatment is challenging for primary care medicine. The USA has faced an iatrogenically induced opiate/opioid epidemic that has killed thousands, with as many as 110 dying daily from a narcotic overdose [1, 2]. In 2016–2017, many thousands of people died from opiate/opioid overdose, especially with the synthetic opioid fentanyl, which is more than 50 times more potent than other prescription opioids To combat this growing threat to public safety, in 2016, new guidelines for prescribing opioids to chronic pain patients were issued by the Center for Disease Control (CDC) [6]. Nearly 116 million Americans suffer from chronic pain, Mol Neurobiol (2021) 58:3335–3346 according to the National Institute on Drug Abuse (NIDA). Those who suffer from severe pain are likely to have worse overall physical and mental health status. Due to the role of big pharmaceutical industries in promoting opioid use and consequent addiction, the estimation is that they may have to pay $150 billion in fines
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