# Cold-sensitive lPBN neurons release enkephalin into vlPAG to relieve pain in mice

- Published: 2026-11-07 16:37 UTC
- Section: Life & Health › Neurotechnology
- Tags: cold-induced analgesia, lateral parabrachial nucleus, enkephalin, periaqueductal gray, opioid receptor signaling, descending pain modulation, nociceptive threshold, Science Advances
- URL: https://realtech.media/news/rt-2f63c390252778c3de1407a8_cold_sensitive_lpbn/

**Researchers identified a hindbrain neuron subset in mice that mediates cold-induced analgesia via enkephalin release and opioid receptors in the periaqueductal gray.**

![Cold-sensitive lPBN neurons release enkephalin into vlPAG to relieve pain in mice](https://realtech.media/media/2026/11/1073389777959ca6.jpg)
*Rama, Wikimedia Commons, CC BY-SA 2.0 fr*

A study in Science Advances describes a subset of cold-responsive neurons in the lateral parabrachial nucleus (lPBN), a thermosensory relay region of the hindbrain, that mediates cold-induced analgesia in mice [1]. Cold, or chemicals that mimic cold, has long been applied to injuries for pain relief, but the underlying neural mechanisms remained unclear [1].

Selective activation of these neurons, and of their projection to the ventrolateral periaqueductal gray (vlPAG), raised the nociceptive threshold. The effect depended on opioid receptor signaling in the vlPAG [1]. Ablation of the neurons attenuated analgesia induced by cold-mimicking chemicals [1].

The authors report that these neurons express the precursor gene of enkephalin, which is released into the vlPAG for pain relief [1]. Activation of cold-responsive neurons in the descending pain modulation circuitry reduced spinal cord responses to noxious stimuli, which suggests a top-down pain modulation pathway [1].

The authors propose this as a central mechanism of cold-induced pain relief and a possible therapeutic target [1]. The work was performed in mice.

## Sources

1. [Science Advances](https://doi.org/10.1126/sciadv.aea3106)

---

Source: RealTech, realtech.media — https://realtech.media/news/rt-2f63c390252778c3de1407a8_cold_sensitive_lpbn/