Have you ever felt like everything hurts after not getting enough sleep? A new study reveals a neurotransmitter involved in pain caused by lack of sleep, indicating a potential new target for treatment.
In sleep-deprived mouse models, the neurotransmitter N-arachidonoyl dopamine (NADA), an endocannabinoid, was reduced in a brain region linked to sensory processing and arousal.
Administration of NADA to this region attenuated the previously increased pain response.
Not surprisingly, sleep problems are common among people who already suffer from chronic pain. But in turn, difficulty sleeping exacerbates the nervous system’s response to potentially painful stimuli and makes pain worse.
Of course, we would expect that loss of sleep would make many things worse. But the causes that cause headaches and body pain after lack of sleep have not been well defined, making treatment more difficult.
“We provide a mechanism for how sleep disruption leads to exaggerated pain, suggesting that harnessing the endocannabinoid system could break the vicious cycle between pain and sleep loss,” says co-senior author Shiqian Shen, an anesthesiologist. and pain physician at Harvard Medical School. .
Shen and colleagues from the United States, China and South Korea conducted tests on mice and found that chronic sleep disruptions made them more sensitive to pain, and this was due to signaling of a part of the brain called the thalamic reticular nucleus (TRN).
The TRN plays a role in regulating alertness and is thought to act as a gatekeeper that controls the flow of sensory information to the cortex, the outer layer of neurons in our brain.
Previous studies in mice have implicated TRN in pain sensitivity. So the team wanted to see if this could apply to the type of pain caused by insufficient sleep.
Mice that underwent five consecutive days of sleep deprivation showed higher sensitivity on tests designed to measure pain response. Measurements of brain signals showed exaggerated activation of specific TRN neurons that project to an area of the thalamus that transmits sensations such as pain, touch and temperature to the cortex.
By examining brain metabolites, the researchers found that levels of the endocannabinoid NADA were lower in the TRN of mice that did not get enough sleep compared to control mice. This decline was only observed in the TRN.
When Shen and his team administered NADA to the TRN of sleep-deprived mice, the increased activation of these signaling neurons in the thalamus region was reversed and the mice no longer showed signs of increased sensitivity to pain.
“Our results suggest that NADA is physiologically important and that chronic sleep disturbances lead to decreased levels of NADA that cause hyperalgesia (increased sensitivity to pain),” the team writes.
Endocannabinoids are lipid-based signaling molecules produced naturally by our bodies. They bind to cannabinoid receptors in the endocannabinoid system, a complex cellular signaling system involved in the regulation of a wide range of bodily functions.
The researchers also found that the activity of cannabinoid receptor 1, involved in the regulation of pain perception, decreased in the TRN of sleep-deprived mice. Next, they demonstrated that blocking the cannabinoid 1 receptor could counteract the beneficial effects of NADA.
This suggests that both the receptor and NADA contribute to increased pain sensitivity in mice when they are sleep deprived.
Endocannabinoids have been implicated in many neurological disorders, including multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, and epilepsy.
It appears that they also play a major role in regulating chronic pain associated with sleep loss. The team hopes that their findings on the role of NADA will lead to more effective therapies.
“These results provide mechanistic insights into the neural circuits underlying chronic hyperalgesia induced by sleep disturbances,” the researchers conclude, “and implicate endocannabinoids as potential mechanistic targets for future studies.”
The research was published in Natural communications.