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Pain is “an unpleasant sensory and emotional experience, associated with real or potential tissue damage, or described in these terms [by the patient]”. This definition by the International Association for the Study of Pain includes acute and chronic pain. The first acts as an alarm signal to trigger a reaction; when you accidentally touch a hot plate, the spike in pain felt forces you to remove your hand. The second, like the inflammatory pain that follows a wound, settles in over time and can become an illness in itself. It is largely based on the action of the brain. In some pathologies, like fibromyalgia, pain can be linked to a deregulation of the nerve mechanisms that produce it naturally. According to the Stopnet survey conducted in 2004, 30% of the adult population in France suffer from chronic pain. This is therefore a major public health issue.
To address it, doctors prescribe a panel of drugs, from simple paracetamol to opioids. Unfortunately, the analgesics on the market are not very effective in treating the pain. Worse, they are causing a whole other epidemic. In the United States, increasing use of opioids, with or without a prescription, caused the death of 64,000 people in 2016. Hence the need for new tactics. A team at the university of Pennsylvania and the Janelia Research Campus in the United States, have just identified, almost by accident, a new therapeutic avenue against chronic pain. Originally working on the neural bases for hunger in mice, these scientists noticed that rodents deprived of food seemed less sensitive to pain, unlike the control mice. They developed a protocol to trigger various types of pain in the mice by subjecting them to chemical, thermal or mechanical stimuli. Depending on the method used, this caused acute or chronic pain, used to differentially analyse both types of response. Result: the mice starved for 24 hours responded less to inflammatory pain than those who had unlimited access to food. However, the mice deprived of food reacted normally to acute pain. Hunger therefore is able to specifically prevent the response to chronic pain.
What is responsible? The AgRP/NPY groups of neurons, already known to activate when we feel hunger. They also have an arbitrary role; they prioritise the importance of the stimuli perceived, in order to give hunger the priority over the chronic pain. By activating them specifically, the scientists observed that the responses to chronic pain disappeared in the mice, leaving their responses to acute pain intact. In particular, one sub-group of these AgRP/NPY neurons, remotely connected to the parabrachial nucleus (a structure which modulates food intake) could be responsible for eliminating inflammatory pain. This mechanism could have been preserved during evolution to ensure the survival of the species. Their brains have been wired to prioritise feeding over healing.
Let us not get it wrong! While fasting is starting to be seen as an additional therapeutic approach to cancer, obviously the idea is not to stop eating in order to feel less pain. The observations made in this study provide an example of an interesting endogenous neural circuit for analgesia and a single entry point to study the pathways that inhibit pain. Do others exist? Are they the same between the sexes? Do they change over the course of a lifetime? The answers to these questions could be the starting point to developing more powerful analgesics, able to target inflammatory pain and leave acute pain intact.
Mariana Alonso is a neuroscientist at the Laboratory of Perception and Memory at Institut Pasteur. Her work looks into neurogenesis and brain plasticity in adults, the neuronal bases of smell linked to behaviour and the relationships between the microbiota, immunity and the brain.