Your genes and your opioids: Pain relief or addiction? Or both?

Last Updated on

March 14, 2019 – Genetic predisposition may help to explain opioid based pain relief, addiction, or the combination of both. In a perfect world, and in battling the rampant opioid crises in the US and other parts of the world, doctors would be able to identify those patients who are prone to opioid addiction and prescribe them non-opioid painkillers that wouldn’t lead to dependence. To do so, they would request from pain patients  genetic testing to see if they carry particular gene variants which render them susceptible for opioid addiction before deciding on a course of anti-pain treatment.

DNA strandsAre there currently potential candidate genes that would allow to test for such a predisposition to addiction? Research shows that indeed there are such candidates. Thus, a common variant of theµ-opioid receptor gene alters opioid sensitivity and has been linked to less pain relief and more susceptibility to addiction. Patients with this particular gene variant are more likely to experience higher levels of pain at standard opioid doses and therefore require higher concentrations for pain relief; high opioid dosages makes addiction more likely in general. This gene variant is named A118G OPRM1 for the nucleotide switch (adenine to guanine) at position 118 in the opioid receptor µ-1 gene. This gene variant leads to the synthesis of an altered µ opioid receptor protein, which loses an important amino acid (asparagine) for sugar attachment and gains an aspartic acid. This loss of the asparagine and the attached sugar chain alters the shape of the protein and likely alters its function.

There are other gene candidates linked to opioid addiction. One family of genes that has been analyzed is involved in dopamine regulation. A dopamine 2 receptor allele (called rs1800497) was compared in drug users and controls and has been linked to high heroin use and unsuccessful methadone use. Another dopamine-related gene, dopamine 4 receptor, contains a region with a variable number of nucleotide repeats; for Genes, the gene may have a stretch with 3 repeats (ATATAT) or a stretch with 6 repeats (ATATATATATAT). People with the higher numbers of repeats (5 to 7 copies of the repeat) have the desire to try new things (called novelty-seeking behavior). Heroin users often have the dopamine 4 receptor gene variants with a higher numbers of repeats.

Besides the A118G OPRM1 gene, other opioid receptor alleles have also been found to be associated with addiction, for example the C17T OPRM1 gene variant. The combination of the G80T opioid receptor δ 1 (OPRD1) gene allele with the normal allele (G80G), as well as the C921T OPRD1 gene, was found to be more prevalent in heroin users than in controls. OPRK1 is considered a candidate gene because it is involved with the stress response and counteracts the euphoria induced through OPRM1. One allele of this gene (rs1051660) was found more frequently in heroin users.

Neurotrophins, or regulatory proteins that modulate neuronal growth, survival, and differentiation, are also candidate genes linked to addiction. Some variants of the neurexin gene are associated with increased impulsive reactions and behaviors that often lead to more drug use.

So, what are opioids in the first place, and are there other types of pain-relieving  medications? Opioids are a group of sleep inducing pain relievers that specifically interact with an opioid receptor. There are three opioid receptors – µ (pronounced mu), κ (kappa), and δ (delta) – and Opioids on a blue background predominantly bind to the µ receptor. Binding at this receptor can alter respiration, gastrointestinal tract motility, physical dependence, euphoria, and pain relief. Opioids are typically used to relieve acute and severe chronic pain. Commonly prescribed opioids include: Dolophine (methadone), codeine, hydrocodone, OxyContin (oxycodone), Duramorph (morphine), propoxyphene, Duragesic (fentanyl), Ultram (tramadol), Dilaudid (hydromorphone), Levo-Dromoran (levorphanol), or Demerol (meperidine).

Unfortunately, most of the other analgesics are not as useful for treating severe pain and are predominantly used for mild-to-moderate pain. Tylenol (acetaminophen) and nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen, and naproxen are non-addictive painkillers that are available over-the-counter. Another class of pain relievers is cox-2 inhibitors (like etoricoxib); they are similar to NSAIDs but have fewer side effects.

Another type of pain reliever that is not available over-the-counter is the class of “combination drugs”, which combine addictive opioids with non-addictive analgesics. Percocet and Ultracet are mixtures of an opioid with acetaminophen, and Percodan is a mixture of oxycodone and aspirin. Fioricet is another, less common combination drug used to treat migraine pain and composed of the barbituate butalbital combined with acetaminophen and caffeine.

Genetic Testing

Knowing that a person will not experience adequate pain relief when given opiates could change surgical procedures. Sometimes patients Pills isolated severe pain during surgery because doctors typically use the minimum amount of drugs required to prevent the development of potential side effects. This risk for severe side effects and severe pain could be reduced if doctors knew which gene variants the patients had. Also, in regards to the management of chronic pain, knowing which patients are most inclined to addiction would allow doctors to focus greater attention on alternatives to medication.

Whatever your status relative to genetic testing might be: Never forget that genes do not dictate your actions. In the case that your genes have been sequenced and you know you carry genes that make you susceptible to addiction, don’t feel defeated and let this override your aspiration to quit. You are perfectly capable of overcoming an addiction; you just might need to work harder.

 

See here a short sequence on opioid dependence and opioid use disorder:

Print Friendly, PDF & Email

 

 

Tags: , , , , , , , , , , ,
About the Author
thassodotcom Ph.D.; Professor in Pharmacology and Toxicology. Senior expert in theragenomic and personalized medicine and individualized drug safety. Senior expert in pharmaco- and toxicogenetics. Senior expert in human safety of drugs, chemicals, environmental pollutants, and dietary ingredients.

Leave a Reply

Optional: Social Subscribe/Login




avatar
  Subscribe  
Notify of

thasso: conditions

thasso: tweets

thasso post: magazine

View my Flipboard Magazine.

thasso: categories

thasso: archives

thasso: simple chat

You must be a registered user to participate in this chat.

  • Ancestry launches DNA health service that will compete with 23andMe October 15, 2019
    Ancestry has long appealed to people eager to learn about their family roots. Now the company known for its popular DNA kits is diving into a new area of discovery—health.
  • Improving research with more effective antibodies October 15, 2019
    A new study points to the need for better antibody validation, and outlines a process that other labs can use to make sure the antibodies they work with function properly.
  • New DNA 'clock' could help measure development in young children October 15, 2019
    Scientists have developed a molecular "clock" that could reshape how pediatricians measure and monitor childhood growth and potentially allow for an earlier diagnosis of life-altering development disorders.
  • DNA fracturing rewires gene control in cancer October 15, 2019
    Understanding the mechanisms that mediate widespread DNA damage in the cancer genome is of great interest to cancer physicians and scientists because it may lead to improved treatments and diagnosis. In this study, a multi-institutional team led by researchers at Baylor College of Medicine has brought attention to genomic structural variation as a previously unappreciated […]
  • Most genetic studies use only white participants – this will lead to greater health inequality October 15, 2019
    Few areas of science have seen such a dramatic development in the last decade as genomics. It is now possible to read the genomes of millions of people in so-called genome-wide association studies. These studies have identified thousands of small differences in our genome that are linked to diseases, such as cancer, heart disease and […]
Top