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GPR37L1 identifies spinal cord astrocytes and protects neuropathic pain after nerve injury

GSE286467 Mus musculus Expression profiling by high throughput sequencing 4 samples Submitted 2025/02/14 Platform GPL30215
Summary
Astrocytes in the spinal cord dorsal horn (SDH) play a pivotal role in synaptic transmission and neuropathic pain. However, the precise classification of SDH astrocytes in health and disease remains elusive. Here we reveal Gpr37l1 as a marker and functional regulator of spinal astrocytes. Through single-nucleus RNA sequencing, we identified Gpr37l1 as a selective GPCR marker for spinal cord astrocytes. Notably, SDH displayed reactive astrocyte phenotypes and exacerbated neuropathic pain following nerve injury combined with Gpr37l1 deficiency. In naïve animals, GPR37L1 knockdown in SDH astrocytes induces astrogliosis and pain hypersensitivity, while Gpr37l1-/- mice fail to recover from neuropathic pain. GPR37L1 activation by maresin-1 increased astrocyte GLT-1 activity and reduced spinal EPSCs and neuropathic pain. Selective overexpression of Gpr37l1 in SDH astrocytes reversed neuropathic pain and astrogliosis after nerve injury. Our findings illuminate astrocyte GPR37l1 as an essential negative regulator of pain, which protects neuropathic pain through astrocyte signaling in SDH.
Published in
GPR37L1 identifies spinal cord astrocytes and protects neuropathic pain after nerve injury
Xu J, Yan Z, Bang S et al. · Neuron 2025 · PMID 39952243 · doi:10.1016/j.neuron.2025.01.012
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Also filed as BioProject PRJNA1209558 and SRA study SRP556755. Searching any of these in the dataset finder brings you back here.

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