pharmacogenetics

Are you Tylenol or Advil person? Alleviating pain through genetics

Chronic pain is not only debilitating and horrible consequence of chronic diseases, trauma, but is also inevitable consequence of medical treatments. Chronic pain is refractory to most of the treatments, but we believe that genetics of pain and pharmacogenetics can substantially improve pain management.

In many cases chronic pain arises due to neural trauma during surgery, drug-induced neurotoxicity or a consequence of degenerative disease. Unfortunately too often people afflicted by chronic pain are losing the battle and resolving to suicide – famous artist Frida Kahlo de Rivera committed suicide because of chronic pain that hunted her after a car accident.

Physicians are unsuccessfully trying to treat chronic pain with many drug classes: antidepressants, antiepileptic drugs, and opioids. Opioids not only are not effective for alleviating chronic pain but morphine also lowers pain sensitivity threshold – this phenomenon known as morphine induced hyperalgesia, which reduces the utility of opioids as a painkiller for prolonged periods of time. Efficacy of other medications such as antiepileptic drug Gabapentin varies tremendously. The risk of chronic development is linked to many factors:

  • insufficient anesthesia in the perioperative period greatly increases chance of developing persistent pain,
  • previous history of trauma since each severe pain episode is “recorded” in the spinal cord and brain,
  • cultural norms and patient’s metal resilience, and
  • genetics – i.e. person’s sensitivity to pain and the inherent ability to metabolize medications including pain killers.

Genetics of pain is a relatively new field of science, but many genes have been shown to play role in genetic pain diseases such as R100W mutation in the NGF in the congenital insensitivity to pain, and multiple mutations in the SCN9A in Primary Eritromyalgia (a.k.a Burning Feet Syndrome), Paroxysmal Extreme Pain Disorder and insensitivity to pain. Causes for more complex pain syndromes such ad fibromyalgia, tempomandibular pain disease, and phantom limb pain have not been found yet, but number of genes have show to be associated with these disorders.

Genetic variation in drug metabolizing and “drug target” genes leads to variable response. For example some people are absolutely convinced that Advil (ibuprofen) is much more effective for them than Tylenol (acetaminophen), or vice versa. In fact there is a very simple explanation – people who are carriers of the CYP2C9 mutations, also known as “poor metabolizers” clear ibuprofen much slower than majority of population thus for them Advil provides stronger pain relief, while Tylenol is metabolized by the CYP2E1 enzyme so the CYP2C9 poor metabolizers have average response.

Anecdotal data from anesthesiologists indicated that red haired women are more sensitive to morphine anesthesia. Indeed, animal models and association studies in humans confirmed that women with mutations in the MC1R gene, which also linked to red hair coloration, have greater pain relief than men.

There are many more examples of genetic differences in response to analgesics including codeine, celecoxib, phenytonin, naproxen and diclofenac and other many other drugs. Pain manamgement can be gretly improved by genetic testing and personalized medical treatments to minimize the time needed to select analgesics are effective for you, and save a lot of suffering.