Brainstem enkephalinergic neural circuit underlying cold-induced pain relief in mice.

Cold-responsive neurons in the lateral parabrachial nucleus of mice increase nociceptive thresholds via projections to ventrolateral periaqueductal gray, with enkephalin release linked to TRPM8-mediated analgesia.

• Why it matters: Cold and cold-mimicking chemicals relieve pain, but the specific brainstem circuit and molecular steps that translate cold signals into analgesia were unclear.
• What they did: The study mapped a cold-responsive lPBN subset, then used neuronal activation or ablation to test effects on cold-induced analgesia; it also assessed Penk expression and TRPM8-dependent pain relief.
• The result: Activating lPBN neurons raised nociceptive thresholds and ablation reduced analgesia from cold-mimicking chemicals; cold-responsive lPBN neurons frequency-dependently released enkephalin into vlPAG, reducing spinal responses to noxious stimuli.

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