Do I need opioids after surgery?
Researchers at the University of Colorado at Boulder, working under the guidance of Professor Linda Watkins, have found in animal experiments that the use of opioids as an analgesic after surgery prolongs the period of soreness by more than 3 weeks and makes specialized immune cells more reactive to pain.
As part of the work, the authors performed a research operation on the abdominal cavity of male rats – laparotomy. Similar operations are routine clinical practice, after which opioids are often used. Drugs of this class are very effective against acute pain, but very little is known about how their effects manifest themselves weeks and months after discontinuation.
In one experiment, half of the rats received the equivalent of an "average" morphine dosage for 7 days after surgery. The second half was injected with saline solution as a placebo.
In another experiment, animals were injected with morphine for 8 days, after which the dose was gradually reduced and the administration was completed on the 10th day. In the third experiment, morphine was administered to animals for 10 days, after which the administration was abruptly stopped.
Before and after therapy, the researchers evaluated the sensitivity of rats to touch, as well as the activity of genes that ensure the expression of inflammatory proteins in the spinal cord.
As a result, it turned out that in morphine-treated rats, the duration of postoperative pain increased by more than 3 weeks. At the same time, the longer they received morphine, the more the pain syndrome was delayed. A gradual reduction in dosage had no effect. This suggests that this phenomenon is not associated with withdrawal syndrome, which causes physical pain.
Professor Watkins describes what is happening as a "double whammy" on specialized immune cells of the central nervous system, known as glial cells. The first stroke – surgical intervention – stimulates Toll-like receptors-4 expressed on their surface, which indicates to the cell the occurrence of a problem, triggers the cascade release of proinflammatory proteins and makes the receptors more sensitive to the second stroke.
The second blow is the effect of morphine, which also stimulates Toll-like receptors-4. The "prepared" glial cells react faster, stronger and longer to this second blow than to the first one. As a result, a stable inflammatory reaction develops, in some cases causing local tissue damage.
In an earlier work, the authors demonstrated that the administration of opiates for only a few days to eliminate pain in peripheral nerves, such as lumbosacral sciatica, can increase and prolong the duration of pain in animals for months, which is partly due to increased expression of pro-inflammatory genes.
In several small clinical studies, an association was found between postoperative opioid use and chronic pain recorded a year after the intervention.
The authors note that the results of animal experiments cannot be directly transferred to humans, but they emphasize the need for additional clinical studies to study the potential relationship between clinical use of opioids and chronic pain.
Article by Peter M. Grace et al. Morphine paradoxically prolongs neuropathic pain in rats by amplifying spinal NLRP3 inflammasome activation. published in the journal Proceedings of the National Academy of Sciences.
Evgenia Ryabtseva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the University of Colorado at Boulder: Opioids after surgery can, paradoxically, prolong pain.