French researchers have identified a molecule of the immune system responsible for some chronic pain. And they have developed an inhibitor, which reduces these pains.
Four million people in France suffer every day, without stop, from a form of pain for which there is almost no treatment: neuropathic pain. It is caused by a lesion of a peripheral nerve, itself caused by various factors such as cancer, shingles, diabetes, a traumatic accident or surgery. The problem is that although the cause of the lesion is healed, the pain persists. But here is perhaps a hope for those who suffer permanently: Jean Valmier, of the Institute of Neuroscience in Montpellier, Didier Rognan, University of Strasbourg, and their colleagues have identified a new molecule responsible for neuropathic pain, as well as than another, which blocks its effects, and therefore pain. Explanations.
An initially acute pain, for example due to a tumor or injury, sometimes becomes chronic: somatosensory or nociceptor neurons, which detect sensory information and pain in the lesion area and transmit it to the brain, function aberrantly and continue to be active even when the cause of the pain is gone. They became hypersensitive. These neurons are located in the dorsal root ganglia of the spinal cord and connect to the neurons of the dorsal horns, which in turn communicate with the brain networks of pain perception. However, current treatments, antiepileptics or antidepressants supposed to reduce the abnormal excitation of nociceptors, only work in 50% of patients and only partially reduce pain, while the side effects are numerous. Hence the need for new effective therapies.
What causes sensitization of pain neurons? The interactions of neurons and the immune system play a crucial role. The immune cells that invade the site of the lesion secrete all kinds of molecules that repair tissue but also promote nervous hypersensitivity. Neuroscientists have identified one of these substances: the FL cytokine. They showed that the injection of this molecule into mice causes symptoms similar to neuropathic pain, as well as the same molecular modifications of spinal cord neurons that lead to a chronicization of pain. This cytokine works by binding to its specific receptor called FLT3,
Inhibit FLT3 can extinguish pain
Would blocking FL’s link to its receiver remove the pain? Inhibitors of FLT3 already exist. They are used to treat some forms of leukemia and indeed decrease the painful symptoms. But these are not specific and cause serious cardiovascular and immune side effects.
Rognan and his colleagues then computerically screened three million molecules and identified a candidate, BDT001, that suppresses FL cytokine binding to its FLT3 receptor. Injected to mice suffering from neuropathic pain, the BDT001 molecule caused in three hours the decrease of various symptoms, including hyperalgesia (the fact that the pain sensation is greater than it should be) and allodynia (a reaction painful to normally painless stimuli). And these effects persisted for 48 hours after a single administration. Following these promising results, the start-up Biodol Therapeutics will launch clinical trials in humans, which could lead to the first specific therapy for neuropathic pain.