Women and Pain

Delving into this topic there is so much dismissive and dis-information out there as to why women experience a greater intensity of pain and are more likely to experience chronic pain.

Let's start here:

In August 2017, The New York Times published a guest op-ed by a man named David Roberts who suffered from severe chronic pain for many years before finally finding relief. The piece went viral,when Dan Rather posted it to his Facebook page with the addendum that it could "offer hope" to some pain patients. However, for many of us in the chronic pain community, particularly women, the piece was regarded with frustration.

The first and most prominent source of annoyance regarding this piece was the part when the author discloses his pain to his employer and it is taken with the utmost seriousness. He is immediately offered leave to find treatment, despite the lack of a definitive diagnosis. This stands in stark contrast to the experiences of many (if not most) women, where our pain is often abruptly dismissed as psychological — a physical manifestation of stress, anxiety, or depression.

We must consider this: women in pain are much more likely than men to receive prescriptions for sedatives, rather than pain medication, for their ailments. One study even showed women who received coronary bypass surgery were only half as likely to be prescribed painkillers, as compared to men who had undergone the same procedure. Women wait an average of 65 minutes before receiving an analgesic for acute abdominal pain in the ER in the United States, while men wait only 49 minutes.

These gender biases in our medical system can have serious and sometimes fatal repercussions. For instance, we remember the study in The New England Journal of Medicine that found that women are seven times more likely than men to be misdiagnosed and discharged in the middle of having a heart attack. Why? Because the medical concepts of most diseases are based on understandings of male physiology, and women have altogether different symptoms than men when having a heart attack. Not surprising and an older study but to return to the issue of chronic pain, 70% of the people it impacts are women. And yet, 80% of pain studies are still conducted on male mice or human men. One of the few studies to research gender differences in the experience of pain found that women tend to feel it more of the time and more intensely than men. While the exact reasons for this discrepancy haven't been pinpointed yet, biology and hormones are suspected to play a role.1

Article after article on the subject notes psychological factors and women being “wired differently.” “Conditions such as anxiety and depression, which are reported in greater numbers in women, may exacerbate the effects of painful conditions, even if the pain itself hasn’t actually intensified.” 2 Here we go again, they may as well change the diagnosis code to hysteria. Yes that is a cheeky statement but we should ask ourselves if our pain was actually addressed, would the disparity in the anxiety/depression diagnosis in women exist? Are we being placated? I think so.

Additionally these articles go on to point to “the fluctuating nature of female hormones may amplify the body’s perception of pain. For instance, “when estrogen levels are low during the menstrual cycle or after menopause, pain receptor activity is elevated, which in turn causes the body to feel more pain..”2 In reality, the lack of testosterone which has been - more heavily researched- and shown to have pain inhibiting properties may be at play more so then fluctuating estrogen levels.

A more recent study published in the journal Brain has perhaps a more accurate explanation. “Women are disproportionately impacted by the burden of chronic pain,” explains the paper. “They are more likely than men to report low back pain, neck pain, orofacial pain and neuropathic pain, and twice as many women report common migraines or headaches. In quantitative evaluation of experimentally induced pain in humans, women show more pain sensitivity than men across several noxious modalities, including mechanical-, electrical-, thermal- and chemical-induced pain.”

Despite this clear disparity, for decades the general scientific consensus on pain perception was that it affected male and female bodies in basically the same way. The problem was, this conclusion wasn’t really based on anything: “A male-biased approach has dominated neuroscience research, including pain, typically with no rationale provided,” the authors note.

This study has two big advantages over previous research: first, it included female subjects; and second, it included human subjects.

“Given the importance of understanding the neurobiological underpinnings of chronic pain across sex, we investigated mechanisms of neuronal hyperexcitability in the rat and human superficial dorsal horn (part of the spinal cord) of males and females,” the researchers explain.

They discovered something interesting. There's a specific kind of protein that lives in our spinal cords known as brain-derived neurotrophic factor, or BDNF for short. It plays an important and complex role in pain processing, amplifying pain signals in the spinal cord over short time spans 4 and doing the opposite long-term. 5

That’s not new – the BDNF gene was first discovered a full 40 years ago now, and many studies have already investigated its role in pain perception. But here’s the thing: remember how we said before that almost all those studies were exclusively conducted in male animals and humans?

“We discovered that … a pathological coupling between KCC2-dependent disinhibition and N-methyl-D-aspartate receptor (NMDAR) potentiation within superficial dorsal horn neurons was observed in male but not female rats,” explains the paper.

Researchers found that two important processes in the spinal cord, KCC2-dependent disinhibition and NMDAR potentiation, were abnormally linked in males while this coupling was not seen in females.

Let's define the key players a little better,

KCC2 is a protein that helps to maintain the balance of ions in nerve cells.

Disinhibition is the process by which inhibitory neurons are prevented from firing, which allows excitatory neurons to fire more easily. Inhibition first of all, is like the sprayer on a hose that is on. The hose is on but nothing is coming out. Disinhibition is your hand squeezing the lever so water can flow. Typically our pain neurons are in an inhibitory state until there is an event that squeezes the lever, so to say, and the pain the neuron fires into the nervous system.

NMDARs are a type of glutamate receptor that is important for learning and memory, but they can also play a role in chronic pain.

The researchers believe that this pathological coupling between KCC2-dependent disinhibition and NMDAR potentiation may be a key mechanism in the differences between how men and women experience pain.

The takeaway is two fold.

1. There is a coupling mechanism involving how pain neurons are activated vs inhibited in men that do not exist in women.

2. There is a well documented difference in how pain complaints are received and treated in the medical community between men and women. Given what we know from our “how it really works” website page. We know that the brain can change and adapt or expand dedicated space to receiving constant stimuli, even pain stimuli.

So perhaps the combination of the coupled mechanism and the neuroplasticity model have contributed to women experiencing pain more intensely and for longer periods of time.

There is a need for development of more personalized therapies, honed as far as possible for the patient’s individual needs. Practitioners coming up in the fields of medicine need to address the differences and need to address women’s pain not dismiss it or attribute it to a mental state. Wombs don't wonder!

1“Women and pain: Disparities in experience and treatment”, Harvard health publishing, Harvard medical school, Oct 19,2017

2 Rachael Rettner, “Women Feel Pain More Intensely Than Men Do”, My Health News Daily, Scientific American, January 23, 2012

3 Annemarie Dedek and others, Sexual dimorphism in a neuronal mechanism of spinal hyperexcitability across rodent and human models of pathological pain, Brain, Volume 145, Issue 3, March 2022, Pages 1124–1138

4 Obata K, Noguchi K. BDNF in sensory neurons and chronic pain. Neurosci Res. 2006 May;55(1):1-10. doi: 10.1016/j.neures.2006.01.005. Epub 2006 Mar 3. PMID: 16516994.

5 Rusanescu, G. and Mao, J. (2015), Immature spinal cord neurons are dynamic regulators of adult nociceptive sensitivity. J. Cell. Mol. Med., 19: 2352-2364. https://doi.org/10.1111/jcmm.12648