Can having chronic, untreated pain impact your immune system? Could it be one of the things that makes certain people more likely to end up with a cytokine storm and more likely to end up on a ventilator? Let’s dive in.
A Facebook Live Discussion
During the coronavirus crisis, I have been on the Regenexx page broadcasting Facebook Live events for an hour each day on Mondays, Wednesdays, and Fridays at 12 noon Pacific/3 pm Eastern. We have discussed various topics, but one that came up the other day was whether having chronic pain somewhere in your body could make you more susceptible to getting the more severe forms of COVID-19 that everyone is trying to avoid. Meaning, the patients who need to be on a ventilator. So let’s jump in.
Pain and the Immune System
In animal models, when you injure nerves, the immune system is adversely impacted (1). In addition, in animals with chronic pain, researchers find potentially harmful methylation of DNA in their white blood cells and brain cells (2). This is the marking of the DNA in cells which determines how the genes function and hundreds to thousands of genes were adversely impacted by the pain in these animals. TMJ patients with chronic pain also have a lowered immune response to a standard challenge (3).
Why is all of this happening? We also know that chronic pain is mediated through the immune system through the back and forth between nerves and immune cells (12). In addition, the immune response that normally involves killing the foreign invader in the body may be one way that chronic pain, in some people, spins out of control. For example, we know that bad pro-inflammation chemicals excreted by certain immune cells may be the spark that starts the bonfire of pain that some people experience every day. In addition, we know that chronic pain places your body in a constant fight or flight response and that cortisol systems that help keep you healthy can get burnt out (13).
The Cytokine Storm
We know that severe coronavirus patients have an inflammatory “cytokine” storm in the lungs that can cause death. This causes the lungs to fill with swelling which reduces the ability to exchange oxygen. More total body inflammation may cause more of that storm. Hence, this could be one of the reasons that some people are being hit harder by COVID-19. Is this important for certain patients or those with chronic pain?
For example, let’s take patients who are overweight, have high triglycerides, are pre-diabetic, and have high blood pressure, which is a state that we in medicine call metabolic syndrome. We believe that patients with metabolic syndrome are more likely to have severe COVID-19 disease (4). One theory of why this happens is that higher levels of systemic inflammation in these patients facilitates the cytokine storm. Meaning that starting a forest fire in a wet forest (the body without chronic inflammation) doesn’t do much, but starting one in a forest that is hot and dry (the body with chronic and widespread inflammation) can burn the forest down.
So how does having chronic pain influence your total body inflammation? First, we know that patients with higher systemic inflammation have more severe low back pain, sciatica, and symptoms of stenosis for longer (5-8). We also know that patients with chronic shoulder pain and a rotator cuff tear with pain despite surgery have evidence of chronic inflammation as the cause of that pain (9). We also know that proinflammatory chemical levels in the body correlate with the amount of total pain someone reports (10).
Hence, if you have chronic pain, it may be because of chronic widespread inflammation. Conversely, your chronic pain may be causing more total body inflammation due to a lack of activity which can cause metabolic syndrome. Either way, that widespread inflammation may cause you to be at higher risk for more severe COVID-19. So what can you do?
What NOT to Do…
All too often, patients mask their pain by taking Tylenol or NSAID drugs like Motrin, Advil, Alleve, Naprosyn, Celebrex, Voltaren, etc… However, physician-scientists have been warning against taking NSAID drugs with COVID-19 due to serious concerns that this will worsen the disease course by hurting the immune system (11). Hence, don’t mask the pain with over the counter drugs.
What Can You Do?
Here are some suggestions:
- Treat the widespread inflammation with supplements. Some good ones with lots of research are high-dose fish oil, curcumin, and glucosamine/chondroitin.
- Figure out what’s causing the pain and get it treated! Meaning that instead of masking the pain, get a diagnosis of why you hurt. Then focus on treatments that may help the damaged area to repair.
- Use this time to get that diagnosis started over telemedicine.
The upshot? Making sure that you keep your pain and inflammation under control is key right now. So if you hurt, there is no better time to figure out why and get that treated! To do that, we have more than 100 specialist physicians available through telemedicine who can see you using your phone, tablet, or computer in an insurance-covered visit!
(1) Herzberg U. Chronic pain and immunity: mononeuropathy alters immune responses in rats. Pain, 59 (1994) 219-225.
(2) Massart R, et al. Overlapping signatures of chronic pain in the DNA methylation landscape of prefrontal cortex and peripheral T cells. Scientific Reports, 2016; 6: 19615 DOI: 10.1038/srep19615
(3) Marbach JJ, Schleifer SJ, Keller SE. Facial pain, distress, and immune function. Brain Behav Immun. 1990 Sep;4(3):243-54.
(4) Bornstein, S.R., Dalan, R., Hopkins, D. et al. Endocrine and metabolic link to coronavirus infection. Nat Rev Endocrinol (2020). https://doi.org/10.1038/s41574-020-0353-9
(5) Klyne D, Barbe F, Hodges P. Systemic inflammatory profiles and their relationships with demographic, behavioural and clinical features in acute low back pain. Brain, Behavior, and Immunity. Volume 60,
2017, Pages 84-92. https://doi.org/10.1016/j.bbi.2016.10.003.
(6) Sainoh T, et al. Correlation among Inflammatory Cytokine Expression Levels, Degree of Disk Degeneration, and Predominant Clinical Symptoms in Patients with Degenerated Intervertebral Discs. Asian Spine J. 2017 Jun;11(3):472-477. doi: 10.4184/asj.2017.11.3.472. Epub 2017 Jun 15. https://www.ncbi.nlm.nih.gov/pubmed/28670416
(7) Weber, K.T., Alipui, D.O., Sison, C.P. et al. Serum levels of the proinflammatory cytokine interleukin-6 vary based on diagnoses in individuals with lumbar intervertebral disc diseases. Arthritis Res Ther 18, 3 (2016). https://doi.org/10.1186/s13075-015-0887-8
(8) Schistad EI, Espeland A, Pedersen LM, Sandvik L, Gjerstad J, Røe C. Association between baseline IL-6 and 1-year recovery in lumbar radicular pain. Eur J Pain. 2014 Nov;18(10):1394-401. doi: 10.1002/j.1532-2149.2014.502.x.
(9) Okamura K, et al. Shoulder pain and intra-articular interleukin-8 levels in patients with rotator cuff tears. Int J Rheum Dis. 2017 Feb;20(2):177-181. doi: 10.1111/1756-185X.12581.
(10) Koch, A., Zacharowski, K., Boehm, O. et al. Nitric oxide and pro-inflammatory cytokines correlate with pain intensity in chronic pain patients. Inflamm. res. 56, 32–37 (2007). https://doi.org/10.1007/s00011-007-6088-4.
(11) Day Michael. Covid-19: ibuprofen should not be used for managing symptoms, say doctors and scientists BMJ 2020; 368 :m1086
(12) Totsch SK, Sorge RE. Immune System Involvement in Specific Pain Conditions. Mol Pain. 2017;13:1744806917724559. doi:10.1177/1744806917724559
(13) Vachon-Presseau T et al, The stress model of chronic pain: evidence from basal cortisol and hippocampal structure and function in humans, Brain, Volume 136, Issue 3, March 2013, Pages 815–827, https://doi.org/10.1093/brain/aws371