Descending locus coeruleus noradrenergic signaling to spinal astrocyte subset is required for stress-induced mechanical pain hypersensitivity - PubMed
2 days ago
- #noradrenergic signaling
- #pain hypersensitivity
- #astrocytes
- The study identifies a circuit involving locus coeruleus descending noradrenergic neurons (LC→SDH-NA neurons) that is activated by acute restraint stress and is necessary for stress-induced mechanical pain hypersensitivity in mice.
- Spinal noradrenaline (NA) released from LC→SDH-NA terminals primarily targets α1A-adrenaline receptors (α1ARs) in Hes5-positive (Hes5+) astrocytes in the spinal dorsal horn (SDH), a subset of astrocytes known to induce pain sensitization.
- Activation of Hes5+ astrocytes reduces the activity of SDH inhibitory neurons (SDH-INs), which normally play a role in pain inhibition. This reduction in IN activity is mediated by A1-adenosine receptors (A1Rs).
- Knockdown of A1Rs in SDH-INs cancels the astrocytic reduction of IN activity and suppresses pain hypersensitivity caused by acute restraint stress.
- The findings suggest that LC→SDH-NA signaling to Hes5+ astrocytes and subsequent astrocyte-mediated reduction of SDH-IN activity are critical for stress-induced mechanical pain hypersensitivity.