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| Status |
Public on Aug 06, 2024 |
| Title |
Persistent changes in nociceptor translatomes govern hyperalgesic priming in mouse models |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Hyperalgesic priming is a model system that has been widely used to understand plasticity in painful stimulus-detecting sensory neurons, called nociceptors. A key feature of this model system is that following priming, stimuli that do not normally cause hyperalgesia now readily provoke this state. We hypothesized that hyperalgesic priming occurs due to reorganization of translation of mRNA in nociceptors. To test this hypothesis we used paclitaxel treatment as the priming stimulus and translating ribosome affinity purification (TRAP) to measure persistent changes in mRNA translation in Nav1.8+ nociceptors. TRAP sequencing revealed 161 genes with persistently altered mRNA translation in the primed state. We identified Gpr88as upregulated, and Metrn as downregulated. We confirmed a functional role for these genes wherein a GPR88 agonist causes pain only in primed mice, and established hyperalgesic priming is reversed by Meteorin. Our work demonstrates that altered nociceptor translatomes are causative in producing hyperalgesic priming.
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| Overall design |
Paclitaxel (Sigma Aldrich, Y0000698) was dissolved in a 1:1 solvent mixture of Kolliphor EL (Sigma-Aldrich) and ethanol. Female Nav1.8-TRAP mice were administered paclitaxel diluted in sterile Dulbecco’s phosphate buffered saline (DPBS; Thermo Scientific) or vehicle solvent intraperitoneally at a dosage of 4 mg/kg every other day, resulting in a cumulative dosage of 16 mg/kg. The animals were tested fro mechanical hypersensitivity until they reached back to baseline measurement. The animals were euthanized, and all dorsal root ganglion were dissected and trap sequencing was performed. The input and the immunoprecipitate fractions were bulk sequenced.
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| Contributor(s) |
Sankaranarayanan I, Ferreira DT, Price TJ |
| Citation(s) |
39149295 |
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| Submission date |
Aug 06, 2024 |
| Last update date |
Sep 12, 2024 |
| Contact name |
Theodore Price |
| E-mail(s) |
Theodore.Price@utdallas.edu
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| Organization name |
The University of Texas at Dallas
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| Street address |
800 W Campbell Rd
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| City |
Dallas |
| State/province |
TX |
| ZIP/Postal code |
75080 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA1144941 |
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