New research has identified a tiny population of neurons that controls inflammatory pain, but not nerve injury pain, by making and releasing the hormone oxytocin. Interestingly, the new group of oxytocin neurons is unusually small—made up of only about 30 cells.
“The two fascinating parts of this story are the small number of cells that can affect behavior with miniscule increases in the circulating concentration of oxytocin, and the ability [of this population] to affect only one type of pain,” says James Eisenach, Wake Forest University, Winston-Salem, US, who was not involved in the new study. “The results suggest that…an analogue of oxytocin [i.e., a molecule similar to the hormone] might be analgesic [i.e., pain relieving], and this is worth exploring,” he adds.
The study, led by Alexandre Charlet, University of Strasbourg, France, and Valery Grinevich, University of Heidelberg, Germany, was published online March 3 in the journal Neuron.
A unique population of oxytocin neurons
Oxytocin, dubbed the “cuddle hormone” for its role in maternal behavior and social bonding, stimulates uterine contractions and is widely used in medicine to induce labor. It is also critical for the milk let-down reflex of lactation.
A growing body of research suggests that oxytocin may also play a role in pain. Studies in rodents have shown that oxytocin can relieve a variety of different types of pain, and a handful of clinical trials have shown that oxytocin can improve pain from back injury, migraine, and irritable bowel syndrome.
In the current study, Charlet, Grinevich, and colleagues were not initially looking at the role of oxytocin neurons in pain, Charlet tells RELIEF. Instead, while examining the role of an area of the brain called the hypothalamus in lactation, they discovered a unique population of neurons, and decided to figure out what those cells do in rats.
To that aim, the researchers used a technique called optogenetics, which uses light to change the activity of cells, to stimulate the oxytocin neurons. They found that the cells affected pain sensation by blocking the function of spinal cord neurons that send pain signals to the brain.
Experiments also showed that the small population of oxytocin neurons also caused a different population of oxytocin neurons in the hypothalamus to release oxytocin into the blood. This circulating oxytocin controlled pain through actions in the peripheral nervous system (i.e., outside the brain and spinal cord).
In a final set of experiments, the researchers analyzed the effects of activating or inhibiting the small oxytocin neuron population on pain relief, using animal models of inflammatory pain and of pain caused by nerve injury (neuropathic pain). Inflammatory pain was modeled by injecting an inflammatory agent into the paws of rats, while neuropathic pain was modeled in the animals by surgically damaging the sciatic nerve. (Both of these models are commonly used by researchers to study pain in animals).
Activation of the oxytocin neurons partially relieved hypersensitivity to touch and heat that results from paw inflammation, but did not affect hypersensitivity to touch seen after nerve injury. Conversely, when the researchers blocked the oxytocin neurons, hypersensitivity following paw inflammation increased; again there was no effect on hypersensitivity following nerve injury.
Overall, the new findings are quite incredible, though in need of replication, Eisenach says. “It’s a pretty amazing story. A system in the brain with a really, really small number of neurons can simultaneously release oxytocin onto [two different populations of neurons, one in the hypothalamus and one in the spinal cord], to affect the behavior of animals and analgesia, selectively only in inflammatory states,” he says. —Allison Marin
To read about the research in more detail, see the related Pain Research Forum news story here.
Allison Marin, PhD, is a neuroscientist-turned-science writer who resides in Pittsburgh, Pennsylvania, US.