Genetic Polymorphisms and Pain

Genetic Polymorphisms: Understanding Their Relationship With Cancer Pain – Clinical Pain Advisor – by Vicki Moore, PhD – June 2020

Cancer pain is no different than any other pain and this article explains why and how genetic factors are critical in determining opioid doses.

The Genetic Connection

In addition to genetic polymorphisms associated with the experience of pain, several SNPs have been linked to responses to pain analgesia, such as with opioid therapy.

Although opioids are often an efficacious therapy for pain related to cancer, patients may show varying responses to opioid treatment in association with SNPs in OPRM1, COMT, ABCB1 and other genes.  

Hypermobile Ehlers-Danlos – NIH GeneReviews

Hypermobile Ehlers-Danlos Syndrome – GeneReviews® – NCBI Bookshelf –Howard P Levy, MD, PhD. – Last Revision: June 21, 2018.

This “book,” published by the NIH, is a  good description of the medical aspects of EDS. The overview below is a quick summary.

Synonyms:

• Benign Joint Hypermobility Syndrome,
• EDS Hypermobility Type,
• EDS Type III,
• Ehlers-Danlos Syndrome Hypermobility Type,
• Ehlers-Danlos Syndrome Type III,
• hEDS,
• Joint Hypermobility Syndrome

Hypermobile Ehlers-Danlos syndrome (hEDS) is generally considered the least severe type of EDS, although significant complications, primarily musculoskeletal, can and do occur.  

Genes may determine vulnerability to COVID-19

Genes May Leave Some People More Vulnerable to Severe Covid-19 – The New York Times – By Carl Zimmer – Jun 2020

Geneticists have turned up intriguing links between DNA and the disease. Patients with Type A blood, for example, seem to be at greater risk.

Why do some people infected with the coronavirus suffer only mild symptoms, while others become deathly ill?

Geneticists have been scouring our DNA for clues. Now, a study by European scientists is the first to document a strong statistical link between genetic variations and Covid-19, the illness caused by the coronavirus.  

Genetic explanation for common group of symptoms

NIH scientists uncover genetic explanation for frustrating syndrome | National Institutes of Health (NIH)

When I first read these symptoms, I immediately thought of EDS with POTS and MCAS, which is a common combination.

Scientists at the National Institutes of Health have identified a genetic explanation for a syndrome characterized by multiple frustrating and difficult-to-treat symptoms, including

• dizziness and lightheadedness,
• skin flushing and itching,
• gastrointestinal complaints,
• chronic pain, and
• bone and joint problems.   

EDS: Description by Natl Org for Rare Disorders (NORD)

Ehlers Danlos Syndromes – NORD (National Organization for Rare Disorders) –

This article, explaining why EDS leads to various kinds of pain, could help your doctor understand why you need such potent pain relievers.

Sometimes, doctors think only about us being extra-flexible (which many of us certainly are not anymore as our joints deteriorate with age) and forget about the wider implications of defective collagen.

The Ehlers-Danlos syndromes (EDS) are a group of related disorders caused by different genetic defects in collagen. Collagen is one of the major structural components of the body.  

The role of genetics in estrogen responses

The role of genetics in estrogen responses: a critical piece of an intricate puzzle – free full-text article /PMC4232287/ – Dec 2014

The estrogens are female sex hormones that are involved in a variety of physiological processes, including reproductive development and function, wound healing, and bone growth.

In addition to the role of estrogens in promoting tissue growth and development during normal physiological states, they have a well-established role in determining susceptibility to disease, particularly cancer, in reproductive tissues.

As with so many other biochemical components at work in our bodies, estrogen has both positive and negative effects and we each react differently depending on how the rest of our body is built. 

A genetic defect that exaggerates pain

A genetic defect that exaggerates all sensations (including pain) – Paul Ingraham • Jul 8, 2019

Got widespread chronic pain? There’s a respectable chance you could be identified by your genes alone.

The largest study of the genetics of chronic pain patients to date found 76 genes that are independent risk factors for it (see Johnston). Interestingly, almost half of these genes are also risk factors for severe depression, and there’s also substantial genetic overlap between chronic pain and

• schizophrenia,
• body-mass index,
• rheumatoid arthritis, and
• post-traumatic stress disorder,

amongst others.  

Management of chronic pain in EDS – part 1

Management of chronic pain in Ehlers–Danlos syndrome: Two case reports and a review of the literature – journals.lww.com –  November 2018 – Part 1

I have a lot to say about this long article, so I’m going to break it into 3 separate posts:

Ehlers–Danlos syndromes (EDSs) are a heterogeneous group of heritable connective tissue disorders involving defective collagen synthesis.

Patients with EDS are prone for chronic myofascial pain, apart from other comorbidities.

Although the initial pathology is commonly nociceptive, progression of EDS leads to neuropathies and central sensitization of pain signals.  

The Landscape of Chronic Pain

The Landscape of Chronic Pain: Broader Perspectives – free full-text /PMC6572619/ – by Mark I. Johnson – May 2019

Here is a recent lengthy review of what’s known about chronic pain: the various aspects of various types of pain under various circumstances.

This article shows the folly of making any numerical one-dimensional measurement of chronic pain, which can arise from a variety of causes, vary greatly over time and location, and make such intrusive incursions into our inner lives.

This special issue on matters related to chronic pain aims to draw on research and scholarly discourse from an eclectic mix of areas and perspectives.  

Personalized Pain Medicine

Personalized Pain Medicine – By Lynn Webster, M.D. – October, 2018

Here Dr. Webster explains how our genes control both pain sensitivity and drug sensitivity. Many of us with EDS find ourselves with the most unfortunate combination of high pain sensitivity and low drug sensitivity (due to metabolic issues).

Below is an edited excerpt from a chapter titled, Pharmacogenetics and Personalized Medicine in Pain Management, that Inna Belfer, MD PhD and I published in Clinics in Laboratory Medicine, Volume 36, Issue 3, September 2016.

Pharmacogenetic therapy in people with pain requires consideration of 2 different genetic substrates to determine the outcome of pharmacotherapy.

1. The first is the genetic contribution to a variety of different pain types, and
2. the second is the genetic influence on drug effectiveness and safety.