One of the forces driving opioid abuse in the United States is chronic pain, which affects 50 to 100 million U.S. adults, with at least 20 million of these experiencing high-impact chronic pain that interferes with their work and life most days or every day.
Laumet working at an inverted microscope looking at living pain-sensing neurons. Courtesy photo.
MSU physiologist Geoffroy Laumet, who recently received a three-year, $150,000, 2020 Rita Allen Foundation Award in Pain, studies the cellular and molecular mechanisms underlying the remission and relapse of pain to decipher how and why it occurs, with the end goal of developing ways to mitigate chronic pain among sufferers.
“Acute pain is normal, even beneficial, in preventing a person from acting inappropriately with an injured body part so it can heal,” said Laumet, assistant professor in the MSU Department of Physiology. “Chronic pain, however, is pain that continues beyond the time it has served its purpose in protecting the body—and can continue for months, even years, after the original injury has fully healed.”
Exacerbating the problem, chronic pain is often resistant to treatment, leading physicians to prescribe larger and larger doses of opiates to ease patient suffering, despite opiates being ineffective against chronic pain.
In trying to determine the origin of chronic pain, Laumet has found that it does not necessarily develop as a continuation of the acute pain that arises after surgery or an injury, but often begins after healing of the original injury and remission of the acute pain has occurred, with the patient feeling well. The pain then recurs without cause, becoming chronic. Such a relapse can occur weeks, even months after the surgery or injury has healed and during which time the patient was pain free.”
Laumet’s research aims to understand the neurobiology of this chronic pain, specifically the physiological mechanisms that normally prevent pain from re-emerging after the acute pain arising from injury, illness or surgery has diminished with healing.
With support from the grant, Laumet and his lab have developed a mouse model to enable them to study the mechanism that they believe prevent pain from recurring. The hope is that through the knowledge they gain from studying this mechanism in greater depth, they can develop the means to prevent chronic pain from developing—and alleviate chronic pain that currently exists.
Laumet’s earlier research found that one of the mechanisms that regulates the balance between remission and relapse of pain involves the molecule Interleukin-10 (IL-10), which normally functions to inhibit inflammation at the site of injury.
Pain-sensing neurons re shown in red and IL-10 in green. Orange indicates pain-sensing neurons that possess the IL-10 receptors.
Laumet and his lab are also investigating IL-10 as part of the mechanism that activates the endogenous opioid system (often referred to as endorphins), which occurs naturally when the body becomes injured, acting as an analgesic without the side effects of synthetic opioids. Laumet suspects that IL-10 achieves this effect by increasing the number of active opioid receptors at the point of injury, which then suppresses the pain of injury.
To further their understanding of IL-10’s functions, Laumet’s lab will induce short, acute pain in the mouse models through a small surgical incision to mimic injury or the injection of chemotherapy, both of which induce pain for about two weeks. After that time, they will allow the model to remain pain-free for an additional two weeks before introducing a stressor or blocking the IL-10 in the spinal column to reinstate pain to test their theory that IL-10 functions to prevent pain relapse after injury recovery, meaning that if it is blocked or its synthesis reduced, pain recurs.
Curiously, they found that blocking IL-10 in mice that have never experienced pain has no effect on the mouse’s state; pain neither appears nor increases. This finding suggests that remission from pain after recovery is not a return to the body’s baseline state before acute pain occurred, but rather from a long-term change in the pain-sensing system following a pain-inducing injury that makes IL-10 necessary to prevent pain relapse.
“If we understand more precisely how IL-10 exists as a mechanism to prevent the relapse of pain and discover why it is more active in some people versus others,” added Laumet, “we might be able to predict who might be more vulnerable to chronic pain in the event of acute injury—and work to prevent that outcome after treatment.
“It also means we might be able to treat those in chronic pain through medication that stimulates the production of IL-10, which in turn might be used as a way to stimulate the endogenous opioid system.”
Each year, the Rita Allen Foundation awards two grants of $50,000 annually for three years in recognition of early-career investigators emerging as leaders in basic pain research whose work on the mechanisms that initiate and propagate pain in the nervous system holds high potential for uncovering new pathways to improve the treatment of chronic pain.
Banner image: Earlier research in MSU researcher Geoffroy Laumet’s lab found that one of the mechanisms that regulates the balance between remission and relapse of pain involves the molecule Interleukin-10 (IL-10), which normally functions to inhibit inflammation at the site of injury. This image shows the nuclei of pain-sensing neurons (blue) and the endogenous opioid system (red) within a living mouse cell. Image credit: Geoffroy Laumet