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Spinal somatostatin-positive interneurons transmit chemical itch.
- Source :
-
Pain [Pain] 2019 May; Vol. 160 (5), pp. 1166-1174. - Publication Year :
- 2019
-
Abstract
- Recent studies have made significant progress in identifying distinct populations of peripheral neurons involved in itch transmission, whereas the cellular identity of spinal interneurons that contribute to itch processing is still a debate. Combining genetic and pharmacological ablation of spinal excitatory neuronal subtypes and behavioral assays, we demonstrate that spinal somatostatin-positive (SOM) excitatory interneurons transmit pruritic sensation. We found that the ablation of spinal SOM/Lbx1 (SOM) neurons caused significant attenuation of scratching responses evoked by various chemical pruritogens (chemical itch). In an attempt to identify substrates of spinal itch neural circuit, we observed that spinal SOM neurons partially overlapped with neurons expressing natriuretic peptide receptor A (Npra), the receptor of peripheral itch transmitter B-type natriuretic peptide. Spinal SOM neurons, however, did not show any overlap with itch transmission neurons expressing gastrin-releasing peptide receptor in the dorsal spinal cord, and the gastrin-releasing peptide-triggered scratching responses were intact after ablating spinal SOM neurons. Dual ablation of SOM and Npra neurons in the spinal cord reduced chemical itch responses to a greater extent than ablation of SOM or Npra neurons alone, suggesting the existence of parallel spinal pathways transmitting chemical itch. Furthermore, we showed that SOM peptide modulated itch processing through disinhibition of somatostatin receptor 2A-positive inhibitory interneuron. Together, our findings reveal a novel spinal mechanism for sensory encoding of itch perception.
- Subjects :
- Action Potentials drug effects
Action Potentials genetics
Angiogenesis Inhibitors pharmacology
Animals
Chloroquine toxicity
Disease Models, Animal
In Vitro Techniques
Interneurons physiology
Luminescent Proteins genetics
Luminescent Proteins metabolism
Lysine analogs & derivatives
Lysine metabolism
Mice
Mice, Inbred C57BL
Mice, Transgenic
Muscle Proteins genetics
Muscle Proteins metabolism
Nitrobenzoates pharmacology
Patch-Clamp Techniques
Proto-Oncogene Proteins c-fos metabolism
Somatostatin genetics
Spinal Cord drug effects
Spinal Cord metabolism
p-Methoxy-N-methylphenethylamine toxicity
tau Proteins genetics
tau Proteins metabolism
Interneurons metabolism
Pruritus chemically induced
Pruritus pathology
Somatostatin metabolism
Spinal Cord pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1872-6623
- Volume :
- 160
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Pain
- Publication Type :
- Academic Journal
- Accession number :
- 30913166
- Full Text :
- https://doi.org/10.1097/j.pain.0000000000001499