Sleep Deprivation Causes Increased Pain Sensitivity

Have you ever experienced that everything hurts after a sleepless night? A recent study has uncovered a neurotransmitter, N-arachidonoyl dopamine (NADA), linked to the pain caused by sleep deprivation, offering potential avenues for treatment. In sleep-deprived mouse models, researchers found reduced NADA levels in a brain region associated with sensory processing and arousal. Administering NADA to this area effectively alleviated the heightened pain response.

SLEEP DEPRIVATION AND PAIN

It’s no surprise that sleep loss can exacerbate various issues, including pain sensitivity. However, the specific pathways leading to headaches and increased bodily pain due to sleep deprivation have not been well understood, making effective treatment challenging. “We provide a mechanism as to how sleep disruption leads to exaggerated pain, suggesting that harnessing the endocannabinoid system might break the vicious cycle between pain and sleep loss,” notes co-senior author Shiqian Shen, an anesthesiologist and pain physician from Harvard Medical School.

EXPLORING THE BRAIN’S ROLE

The study conducted tests on mice, revealing that chronic sleep disruption increased their sensitivity to pain. This heightened sensitivity was attributed to signalling from a brain region known as the thalamic reticular nucleus (TRN), which plays a role in regulating alertness and controlling sensory information flow to the cortex.

UNDERSTANDING NADA’S ROLE

Previous research had implicated the TRN in pain sensitivity in mice. The team wanted to investigate whether this also applied to pain resulting from sleep deprivation. Mice subjected to five consecutive days of sleep deprivation exhibited increased sensitivity to pain in tests. Brain signal measurements showed exaggerated activation of specific neurons in the TRN, which project to the thalamus, a region responsible for relaying sensations like pain, touch, and temperature to the cortex.

Examining brain metabolites, the researchers discovered that NADA levels were lower in the TRN of sleep-deprived mice compared to control mice. This drop was specific to the TRN. When NADA was administered to the TRN of sleep-deprived mice, the increased activation of neurons signalling to the thalamus region was reversed, and the mice no longer displayed heightened pain sensitivity.

ENDOCANNABINOID SIGNALING

Endocannabinoids are naturally produced lipid-based signalling molecules in the body that bind to cannabinoid receptors within the endocannabinoid system, regulating various bodily functions. The study also found that cannabinoid receptor 1 activity, involved in pain perception, decreased in the TRN of sleep-deprived mice. Blocking cannabinoid receptor 1 counteracted NADA’s beneficial effects, suggesting that both the receptor and NADA contribute to increased pain sensitivity in sleep-deprived individuals.

POTENTIAL TREATMENT PATHWAYS

Endocannabinoids have been linked to various neurological disorders, and this study suggests their role in regulating chronic pain associated with sleep loss. The researchers hope that their findings on NADA’s role will pave the way for more effective therapies, stating, “These findings provide mechanistic insights into the neuronal circuitry underlying chronic sleep disruption-induced hyperalgesia and implicate endocannabinoids as potential mechanistic targets for future study.”

The research has been published in Nature Communications.

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