Neurons in the caudal ventral lateral medulla mediate descending pain control

Nat Neurosci, 2023 · DOI: 10.1038/s41593-023-01268-w · Published: April 1, 2023

Simple Explanation

The brain can change how we feel pain through circuits that travel down the spinal cord. This study finds specific brain cells in the medulla that, when turned on by something painful, actually lessen pain by using another brain area (locus coeruleus) and a chemical (noradrenaline) in the spinal cord. These brain cells in the medulla, called VLMTH neurons, use a "feed-forward inhibition" system. When something hurts, these cells activate and then send signals to decrease pain responses. The study also shows that this pain-reducing pathway is needed for the body's natural way of handling pain when faced with another strong sensation. This means the VLM–LC pathway helps the body manage pain in different situations.

Study Duration

Not specified

Participants

Mice, aged 7-12 weeks

Evidence Level

Not specified

Key Findings

1
Catecholaminergic neurons in the caudal ventrolateral medulla (cVLM) are activated by noxious stimuli.
2
Activation of cVLMTH neurons suppresses nociceptive responses, specifically to heat.
3
cVLMTH neurons are connected to a descending locus coeruleus (LC) – spinal cord (SC) pathway, and this pathway is required for counter-stimulus induced analgesia.

Research Summary

The study identifies catecholaminergic neurons in the caudal ventrolateral medulla (cVLM) that are activated by noxious stimuli and produce bilateral feed-forward inhibition that attenuates nociceptive responses. This pathway involves the locus coeruleus (LC) and noradrenalin in the spinal cord and is sufficient to attenuate injury-induced heat allodynia and is required for counter-stimulus induced analgesia to noxious heat. The findings define a component of the pain modulatory system that regulates nociceptive responses, expanding the understanding of inputs to the LC descending pain pathway.

Practical Implications

Pain Management

Targeting the cVLM pathway might provide a means to both investigate and treat pain, potentially leading to new therapeutic strategies for chronic pain conditions.

Drug Development

The identification of specific molecular targets (e.g., α2-adrenergic receptors) within the cVLM-LC-SC circuit could facilitate the development of more selective and effective analgesics.

Understanding Pain Modulation

The study provides a deeper understanding of the brain's endogenous pain control mechanisms, which could inform the development of personalized pain management strategies.

Study Limitations

1
The study primarily focused on heat-related pain responses, and the generalizability of the findings to other types of pain (e.g., mechanical, inflammatory) may be limited.
2
The research was conducted in mice, and further studies are needed to determine whether the cVLM-LC-SC pathway plays a similar role in human pain modulation.
3
The precise afferent inputs to cVLMTH neurons from spinal cord projection neurons remain unclear, requiring further investigation to fully elucidate the circuit.

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