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Grpr expression defines a population of superficial dorsal horn vertical cells that have a role in both itch and pain. | LitMetric

AI Article Synopsis

  • Neurons expressing the gastrin-releasing peptide receptor (GRPR) in the dorsal horn of the spinal cord play a significant role in itch pathways, but many are identified as vertical interneurons associated with pain perception.
  • A study using a specialized mouse line showed that these GRPR cells are concentrated in specific spinal laminae, are glutamatergic, and make up about 15% of excitatory neurons in that area, indicating distinct neurochemical profiles.
  • Unexpectedly, these GRPR neurons received direct inputs from nociceptive sensory neurons and were activated by both painful and itchy stimuli, suggesting they contribute to both pain and itch signaling in spinal cord circuits.

Article Abstract

Neurons in the superficial dorsal horn that express the gastrin-releasing peptide receptor (GRPR) are strongly implicated in spinal itch pathways. However, a recent study reported that many of these correspond to vertical cells, a population of interneurons that are believed to transmit nociceptive information. In this study, we have used a GRPR CreERT2 mouse line to identify and target cells that possess Grpr mRNA. We find that the GRPR cells are highly concentrated in lamina I and the outer part of lamina II, that they are all glutamatergic, and that they account for ∼15% of the excitatory neurons in the superficial dorsal horn. We had previously identified 6 neurochemically distinct excitatory interneuron populations in this region based on neuropeptide expression and the GRPR cells are largely separate from these, although they show some overlap with cells that express substance P. Anatomical analysis revealed that the GRPR neurons are indeed vertical cells, and that their axons target each other, as well as arborising in regions that contain projection neurons: lamina I, the lateral spinal nucleus, and the lateral part of lamina V. Surprisingly, given the proposed role of GRPR cells in itch, we found that most of the cells received monosynaptic input from Trpv1-expressing (nociceptive) afferents, that the majority responded to noxious and pruritic stimuli, and that chemogenetically activating them resulted in pain-related and itch-related behaviours. Together, these findings suggest that the GRPR cells are involved in spinal cord circuits that underlie both pain and itch.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9756441PMC
http://dx.doi.org/10.1097/j.pain.0000000000002677DOI Listing

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