A Central Somatic Transmission Mediates Proprioceptive Facilitation of Muscle Pain

Proprioception, often described as a sixth sense to perceive body position and muscle contraction, has been increasingly implicated in the development and maintenance of chronic pain, yet the underlying mechanisms remain unclear. Here, we identify the functional expression of TRPA1 in proprioceptive mesencephalic trigeminal nucleus (MeV) neurons in a mouse model of orofacial muscle pain. TRPA1 sensitization enhances somatic secretion from MeV neurons, thereby promoting the progression and persistence of inflammatory pain by disinhibiting descending pain control from the neighboring noradrenergic locus coeruleus (LC^NE) neurons. Local GABAergic neurons that provide input to LC^NE neurons serve as a key downstream target of MeV somatic volume transmission, forming a critical relay that transduces signals from the MeV to the LC^NE system. Thus, these findings reveal a previously unrecognized somatic volume transmission that links proprioceptive and nociceptive circuits and provides a central mechanism for persistent muscle pain.