How can thirty little neurons reduce pain?

Several studies have demonstrated the role of oxytocin, a molecule involved in sexual reproduction, in pain relief. Approximately 50,000 neurons located at the center of the hypothalamus secret a neuropeptide with multiple effects. An international team analyzed the oxytocinergic center in rats and managed to isolate the “pain-relief center,” consisting of thirty neurons. How can inflammatory pain be reduced by so few neurons?

For several years, hypotheses have been formulated suggesting the existence of small neuron subpopulations with very specific roles in the oxytocinergic center, but until now the idea had never been confirmed. Recently, a team of international researchers coordinated in France by Alexandre Charlet from the Institute of Cellular and Integrative Neuroscience (CNRS/University of Strasbourg) and in Germany by Valérie Grinevich has shed new light on the question. They have identified a pain control center which consists of about thirty neurons responsible for the production of oxytocin in the blood and spinal column. The release mechanism for the molecule during the experience of pain was then studied. The research was published in Neuron.

The scientists mapped out the pathways in order to better understand the dialogue between the oxytocinergic center and the different targets. To do so, they began by studying the neuroanatomy of the oxytocinergic center in rats (which is very close to humans’). The scientists were able to observe about thirty “small” parvocellular neurons in the paraventricular nucleus which were connected to "big" magnocellular neurons in another region of the hypothalamus and to deep layers of the spinal cord. What mechanism was triggered in case of pain (burning, pinching, cutting, etc.)?

The deep layers of the spinal cord are the area where the sensory message from the affected nerves is coded and sent to other neurons, including the oxytocinergic center where the thirty neurons are located. These thirty neurons activate the magnocellular neurons that release oxytocin into the blood, targeting the peripheral neurons that send the message to the brain that is responsible for the sensation of pain. The oxytocin puts them “to sleep,” leading to a reduction in pain. Meanwhile, thanks to their extensions, known as axons (which can measure up to 1 meter in length!), the thirty neurons release oxytocin into the deep layers of the spinal cord.

Thus, thirty little neurons (among the ninety billion in our brain!) have a double analgesic effect that contributes to decreasing the transmission of the pain message to the brain.

Alexandre Charlet, one of the studies co-authors, says he hopes to "find genetic markers that can activate or inhibit specifically the thirty neurons in order to better mitigate the symptoms of patients with pathological pain, while minimizing side effects.” The research team is continuing to explore the rest of the oxytocinergic center to determine the circuits which modulate emotion and clarify the role of oxytocin in different behaviors such as orgasm, social recognition, empathy, anxiety, etc.
Source: Alexandre Charlet, Valery Grinevich et al. A new population of parvocellular oxytocin neurons controlling magnocellular neuron activity and inflammatory pain processing, in Neuron, March 3, 2016.

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