Over the last few weeks, as I’ve studied the inflammasome in more and more detail, I’ve been learning about the human body’s inflammatory response, in general as well as in the particular. This was information left out of my high school biology class, so I’ve been giving myself a primer.
I’m especially interested in this now, as I think I’ve sustained a rotator cuff injury, and it smarts something bad.
Yesterday, I came across this brief video that goes step by step into the inflammatory process. I’ve highlighted a passage in the transcription below.
Inflammation is a local immune response to tissue injury or infection, experienced as heat, redness, edema, pain, and loss of function. Immediately after injury, inflammation begins with brief vasoconstriction of the local blood vessels to reduce blood loss, and formation of a clot to stop the bleeding.
Then, stimulated by cell injury and death, local cells release vasoactive chemicals such as prostaglandins and histamine to dilate local blood vessels, leading to increased blood flow to the area. These chemicals also cause endothelial cells in small blood vessels to contract, opening spaces between them. This increased capillary permeability allows fluids and proteins to pass from the blood into the tissue.
Next, during a multi-stage process called chemotaxis, circulating immune cells called neutrophils move out of the blood vessels to the site of injury and destroy pathogens and damaged cells. Chemotaxis begins when cells at the injury site release messenger molecules called chemoattractants, which cause local endothelial cells and circulating neutrophils to stick together.
Next, in a process called diapedesis, neutrophils squeeze through the endothelial gaps. The neutrophils migrate to the injury site by following a chemotactic gradient. Upon arrival, the neutrophils encounter bacteria, engulf them, and digest them in a process called phagocytosis.
After destruction of the bacteria and removal of cellular waste, tissue repair begins when locally produced growth factors cause local fibroblasts to begin dividing rapidly and secreting large quantities of collagen to reinforce the wound.
Anti-inflammatory drugs inhibit inflammation by blocking production of inflammatory chemicals. The most common drugs for inflammation are non-steroidal anti-inflammatory drugs, or NSAIDs, such as aspirin and ibuprofen. They [target] an enzyme called cyclooxygenase, or COX, [which will inhibit] the production of prostaglandins and several other inflammatory chemicals, thus reducing vasodilation, edema, and pain associated with inflammation.
All well and good, right? Basic, straightforward microbiology. (Props to BRog for catching an error in the video’s explanation about COX.)
Well, I currently have what I fear is a torn rotator cuff, and I’ve been taking NSAIDs off and on when the pain has flared. And this got me thinking: if you take the NSAID and interrupt this process, wouldn’t that make it harder for the injury to heal? Just from the basic description above, it seems like those chemicals are central to the healing process.
Researchers at McGill University in Montreal have found evidence that indicates just this. The Guardian reports:
Using drugs like ibuprofen and steroids to relieve short-term health problems could increase the chances of developing chronic pain, new research suggests.
Normal recovery from a painful injury involves inflammation – the body’s natural reaction to injury and infection – and new research suggests blocking inflammation with drugs could lead to harder-to-treat issues.
[...]
To understand the transition from acute to chronic lower-back pain, researchers followed 98 patients with acute lower-back pain for three months.
They also examined the mechanisms of pain in both humans and mice, and found that neutrophils—a type of white blood cell that helps the body fight infection—play a key role in resolving pain.
Blocking these cells in mice prolonged the pain for up to 10 times the normal duration.
Treatment with anti-inflammatory drugs and steroids such as dexamethasone and diclofenac also produced the same result, although they were effective against pain early on.
(My emphasis.) Additionally, the researchers conducted an analysis of more than 500,000 patients in the UK BioBank study and found that those who took NSAIDs were more likely to have continued pain two to six years on. The results were published in Science Translational Medicine.
As the Guardian article states, “It may be that inflammation has a protective effect, such as preventing acute pain from becoming chronic, and that overly reducing it may be harmful.”
The researchers, led by Marc Parisien, Lucas Lima and Concetta Digostino, caution that this is a small, preliminary study. Another expert consulted, Dr. Franziska Denk, stressed that no one should be adjusting their pain medication schedule based on these findings, as they need to be replicated, preferably in a larger cohort.
Still, the findings comport with what basic biochemistry tells us. If we interrupt the healing process, would it not make sense that that process would take longer?
The researchers, in their discussion of results, say nearly the same thing.
These results ... reemphasized the perhaps counterintuitive concept that an active biological process underlies pain resolution rather than pain progression to chronic status. Our results suggest that this process is impaired in those who do not resolve acute pain over time and suggest time stratification of a cascade of processes resulting in a return to a normal, no-pain state (34)—in a fashion similar to timely processes involved in wound healing (35, 36)—and thus would require gene expression probing at many more time points to decipher the complete phenomenon of pain resolution. Nonetheless, our findings are in line with the observation that the beginning of the inflammatory process programs its resolution (34), and it is thus the failure to initiate an appropriate inflammatory response that may lead to chronic pain.
(Emphasis mine.)
Personally, this rotator cuff problem (if that’s what it is) is a bear, and I’ll take NSAIDs as needed. I do have diclofenac (brand name Voltaren) for a more direct path of relief, but that also was implicated by the study. It seems that those who have decided to grin and bear it all these years may have had the right instincts.
So I’m going to consult my doctor.