Researchers have identified a specialized multisynaptic circuit loop that specifically drives chronic mechanical pain while remaining inactive during normal, protective sensation. This neural pathway originates in the spinal cord, ascends through the thalamus to the primary somatosensory cortex, and returns to the spinal cord via the lateral superior colliculus and OPRM1+ neurons in the medulla. Experiments using mouse models of nerve injury and inflammation demonstrate that silencing any node in this loop can eliminate mechanical hypersensitivity and restore normal pain thresholds. Conversely, repetitive activation of this circuit in healthy subjects is sufficient to induce persistent pain states and associated anxiety-like behaviors. These findings distinguish the mechanisms of chronic pain from acute nociception, offering precise cellular targets for therapeutic intervention. Consequently, targeting this specific brain-spinal cord loop may allow for the treatment of chronic suffering without impairing the body's essential ability to detect immediate physical threats.

References:

• Wang Q, Lee J H, Nachtrab G, et al. Deconstruction of a spino-brain–spinal cord circuit that drives chronic pain[J]. Nature, 2026: 1-10.