Basic pain sensation is about survival , acute pain is an important signal of physical injury, however, when acute pain develops into chronic pain, it becomes a disease that needs treatment.
Over 30% of the world’s population has experienced chronic pain, which creates a huge financial burden. Take the US data as an example. In 2010, the US medical system spent US$560 billion on chronic pain treatment alone, and the productivity loss caused by chronic pain was as high as US$635 billion.
Chronic pain recurs repeatedly, and various treatment methods usually only relieve temporary pain, not a complete cure, and prevent acute pain from turning into chronic pain Pain, which stifles the formation of chronic pain at its source, becomes very meaningful.
On this issue, scientists from McGill University in Canada have made an unexpected discovery, the use of non-steroidal steroids in traditional treatment regimens. Anti-inflammatory drugs(NSAIDs)have been questioned as first-line drugs for pain relief, and could even rewrite pain management guidelines, that is—in Early use of anti-inflammatory drugs for pain relief will increase the risk of later progression to chronic pain. The study was published May 11 in Science Translational Medicine.
chronic inflammation is inseparable from the nervous system and immune system The interaction of circulating immune cells is recruited to the damaged tissue site/inflammation site, releasing various inflammatory mediators, chemokines, lipids and proteases, acting on peripheral nerves, regulating the generation of pain sensation. Based on this, scientists believe that immune cells also play a role in the transformation of acute pain into chronic pain.
The researchers first studied 98 patients with low back pain（low back pain） object, to explore why patients have different disease outcomes 3 months after an acute low back pain attack—some patients experience pain relief after 3 months, while others develop chronic low back pain (p. The 11th edition of the International Classification of Diseases defines pain for more than 3 months as chronic pain).
at the acute pain period(t0)and at the 3-month follow-up< /span>(t1)The peripheral blood of the patients was collected separately, and the pain relievers were analyzed and compared（resolved pain, R) and persistent pain (persistent pain, P, that is, people who develop chronic pain) , changes in peripheral blood immune cells.
The results showed that,over time, the proportion of neutrophils in the peripheral blood of patients with pain relief increased. ratio was gradually reduced, and patients who developed chronic pain had little change in the proportion of neutrophils throughout the course of the disease.
<600">in acute pain All patients with low back pain showed activation of neutrophils and inflammatory response, but the intensity of inflammatory response in patients with pain relief was 75% higher in the early stage than in patients with persistent pain, and these inflammation-related pathways were gradually downregulated later (“open high and walk low”), while the degree of inflammatory response in patients with persistent pain was not significantly down-regulated after 3 months(“open in the middle and walk in the middle” ).
Researchers speculate that this kind of inflammatory response of “high opening and low walking” (mainly the high level of pain in the early stage of pain). inflammatory response), may be more conducive to rapid recovery of pain and avoid progression to chronic inflammation.
to test whether this idea is applicable to other chronic pain conditions , the researchers repeated the above experiment in 30 patients with temporomandibular joint remission disorder syndrome(temporomandibular joint pain, evident during chewing and mouth opening) , the results once again proved that patients with pain relief had significantly higher inflammatory responses in the acute pain stage thanThose who developed chronic pain after 3 months, in other words, the intensity of the early inflammatory response influenced whether acute pain became chronic.
The question is, if suppressing the inflammatory response during an acute pain attack, will it increase the risk of developing chronic pain later?
The researchers constructed mouse pain models in three different ways, including chronic sciatic nerve injury, injection of nerve growth factor, and injection of complete Freund’s adjuvant Create inflammatory damage.
During the acute pain phase, mice were injected with anti-inflammatory analgesics, such as dexamethasone or nonsteroidal, for 6 consecutive days Anti-inflammatory drug(diclofenac), although the pain of the mice was relieved during the injection period, the overall duration of pain was longer than that of the control group(saline injection)extended by a full 2 times.
and if injected into painful mice during acute pain Analgesics with anti-inflammatory effects, such as gabapentin, lidocaine or morphine, relieve pain in mice, and the duration of pain does not prolong, indicating that the use of anti-inflammatory analgesics in the early stage of pain will indeed make the course of pain Prolonged (similar to developing chronic inflammation), while non-anti-inflammatory analgesics have no such effect.
injection of anti-Ly6 antibody in acute pain phase Neutrophils in mice can also be observed to prolong the course of pain; pain mice were injected with neutrophils or neutrophil-specific protein S100A8 at the same time as the anti-inflammatory drug dexamethasone was injected into the pain site. /A9, can counteract the prolonged effect of dexamethasone on the duration of pain, suggesting that neutrophils play an important role in the inflammatory response during acute pain.
Through a series of rigorous animal experiments, researchers can finally Determination: Whether acute pain is transformed into chronic pain depends on the intensity of the early inflammatory response, and the use of anti-inflammatory analgesics to suppress the inflammatory response at this stage will lead to prolonged pain duration.
Finally, in order to verify the effect of anti-inflammatory analgesic/non-anti-inflammatory analgesic use on the occurrence of chronic pain in the population , the researchers analyzed the disease status and medication history of volunteers who reported a history of back pain in the UK Biobank database, and the conclusions were consistent with animal experiments-Use of non-steroidal steroids during acute pain The risk of developing chronic back pain was 1.76 times higher in patients taking anti-inflammatory drugs than in patients taking non-anti-inflammatory analgesics(P=2.0 × 10−5) , 2-6 years after the onset of acute back pain, these patients still suffer from back pain from time to time.
“Non-steroidal anti-inflammatory drugs have been the drug of choice for pain attacks for decades, but our study suggests that this short-term Treatment may be associated with long-term pain,” concludes researcher Jeffrey Mogil.
Maybe it’s time to reconsider the way we treat acute pain, after all we have a lot of non-anti-inflammatory drugs in addition to NSAIDs Of course, more clinical trials are needed before pain treatment guidelines can be rewritten.
References[1]Parisien M, Lima LV, Dagostino C, et al. Acute Inflammatory response via neutrophil activation protects against the development of chronic pain. Sci Transl Med. 2022;14(644):eabj9954. doi:10.1126/scitranslmed.abj9954[2]Cohen SP, Vase L, Hooten WM. Chronic pain: an update on burden, best practices, and new advances. Lancet. 2021;397(10289):2082-2097. doi:10.1016/S0140-6736(21)00393-7
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