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Somatosensory cortex and central amygdala regulate neuropathic pain-mediated peripheral immune response via vagal projections to the spleen
Ist Teil von
Nature neuroscience, 2024-03, Vol.27 (3), p.471
Ort / Verlag
United States
Erscheinungsjahr
2024
Quelle
MEDLINE
Beschreibungen/Notizen
Pain involves neuroimmune crosstalk, but the mechanisms of this remain unclear. Here we showed that the splenic T helper 2 (T
2) immune cell response is differentially regulated in male mice with acute versus chronic neuropathic pain and that acetylcholinergic neurons in the dorsal motor nucleus of the vagus (ACh
) directly innervate the spleen. Combined in vivo recording and immune cell profiling revealed the following two distinct circuits involved in pain-mediated peripheral T
2 immune response: glutamatergic neurons in the primary somatosensory cortex (Glu
)→ACh
→spleen circuit and GABAergic neurons in the central nucleus of the amygdala (GABA
)→ACh
→spleen circuit. The acute pain condition elicits increased excitation from Glu
neurons to spleen-projecting ACh
neurons and increased the proportion of splenic T
2 immune cells. The chronic pain condition increased inhibition from GABA
neurons to spleen-projecting ACh
neurons and decreased splenic T
2 immune cells. Our study thus demonstrates how the brain encodes pain-state-specific immune responses in the spleen.