Mispositioned Neurokinin-1 Receptor-Expressing Neurons Underlie Heat Hyperalgesia in Disabled-1 Mutant Mice
| Autor: | Wang, Xidao, Yvone, Griselda M, Cilluffo, Marianne, Kim, Ashley S, Basbaum, Allan I, Phelps, Patricia E |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Hot Temperature Neuronal lateral spinal nucleus Knockout Neurokinin-1 Dab1 Nerve Tissue Proteins reeler Lmx1b Mice Receptors Genetics Animals pain superficial dorsal horn Extracellular Matrix Proteins Pain Research Serine Endopeptidases Neurosciences Posterior Horn Cells Reelin Protein nervous system Spinal Cord Hyperalgesia Neurological Chronic Pain Cell Adhesion Molecules Signal Transduction |
| Zdroj: | eNeuro, vol 6, iss 3 |
| Popis: | Reelin (Reln) and Disabled-1 (Dab1) participate in the Reln-signaling pathway and when either is deleted, mutant mice have the same spinally mediated behavioral abnormalities, increased sensitivity to noxious heat and a profound loss in mechanical sensitivity. Both Reln and Dab1 are highly expressed in dorsal horn areas that receive and convey nociceptive information, Laminae I-II, lateral Lamina V, and the lateral spinal nucleus (LSN). Lamina I contains both projection neurons and interneurons that express Neurokinin-1 receptors (NK1Rs) and they transmit information about noxious heat both within the dorsal horn and to the brain. Here, we ask whether the increased heat nociception in Reln and dab1 mutants is due to incorrectly positioned dorsal horn neurons that express NK1Rs. We found more NK1R-expressing neurons in Reln-/- and dab1-/- Laminae I-II than in their respective wild-type mice, and some NK1R neurons co-expressed Dab1 and the transcription factor Lmx1b, confirming their excitatory phenotype. Importantly, heat stimulation in dab1-/- mice induced Fos in incorrectly positioned NK1R neurons in Laminae I-II. Next, we asked whether these ectopically placed and noxious-heat responsive NK1R neurons participated in pain behavior. Ablation of the superficial NK1Rs with an intrathecal injection of a substance P analog conjugated to the toxin saporin (SSP-SAP) eliminated the thermal hypersensitivity of dab1-/- mice, without altering their mechanical insensitivity. These results suggest that ectopically positioned NK1R-expressing neurons underlie the heat hyperalgesia of Reelin-signaling pathway mutants, but do not contribute to their profound mechanical insensitivity. |
| Databáze: | OpenAIRE |
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