A new avenue for managing pain without increasing opioids

Nearly 30% of adults suffer from chronic pain according to the National Institute of Health and Medical Research (Inserm). Some of them take opioids, medications that relieve pain, such as tramadol, morphine and fentanyl. These medications are generally effective in the short term. But, over time, patients with chronic pain face two problems: tolerance and hyperalgesia, which is a greater sensitivity to opioid-induced pain. So, to obtain the same analgesic effect as at the beginning, they must increase the doses and, over time, the effectiveness decreases.

One way to avoid increasing opioid doses

Researchers from the University of Montpellier, Inserm and CNRS, in collaboration with the company Biodol Therapeutics, worked on this subject. The objective of their study, published in the journal Nature Communicationswas to find solutions for these patients so that they no longer have to increase doses to relieve their pain. To do this, they first worked to understand the reasons for tolerance and hyperalgesia: co-expression of the MOR receptor and the FLT3 tyrosine kinase receptor, which would participate in the development of these two phenomena.

Next, the scientists used an inhibitor called BDT001 to disrupt the effect of this newly identified FLT3 receptor. The test was carried out on mice, administering BDT001 at the same time as morphine. Results, the inhibitor allowed, on the one hand, to prevent the appearance of tolerance and hyperalgesia, and on the other hand, to amplify the analgesic potential of morphine without increasing the adverse effects of opioids.

In addition, in rodents that have already been exposed to opioids, this treatment with the inhibitor BDT001 made it possible to eliminate the phenomena of tolerance and hyperalgesia. Thus, the effectiveness of morphine was like the first doses of opioids, or even better.

Increasing the quantities of opioids poses risks

“Our results suggest that the combination of morphine and FLT3 inhibitors could become a promising avenue for the management of chronic pain in order to safely harness the power of opioids, without the risk of increasing doses or even decreasing them. to reduce all side effects”, explains Cyril Rivat, researcher at the Montpellier Neuroscience Institute (INM), in a communiqué.

A major health issue because, in addition to the effects of tolerance and hyperalgesia, the increase in the quantities of opioids consumed can lead to side effects, such as breathing difficulties, and the risk of addiction. According to the World Health Organization (WHO)in 2019, almost 80% of the 0.6 million deaths attributable to drug use were related to opioids, with the cause of death being overdose in approximately 25% of these cases.