The cellular basis of protease activated receptor type 2 (PAR2) evoked mechanical and affective pain
| Autor: | Serge N. Belugin, Armen N. Akopian, Andi Wangzhou, Pradipta R. Ray, Juliet Mwirigi, Michael D. Burton, Moeno Kume, Theodore J. Price, Josef Vagner, Ayesha Ahmad, Stephanie Shiers, Shayne N. Hassler, Gregory Dussor, Dhananjay K. Naik, Scott Boitano |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Population Sensory system Biology 03 medical and health sciences 0302 clinical medicine medicine Protease-activated receptor education Receptor Protease-activated receptor 2 030304 developmental biology G protein-coupled receptor 0303 health sciences education.field_of_study Visceral pain General Medicine Sensory neuron 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Knockout mouse Nociceptor medicine.symptom Neuroscience 030217 neurology & neurosurgery |
| Popis: | Protease-activated receptor type-2 (PAR2) has long been implicated in inflammatory and visceral pain, but the cellular basis of PAR2-evoked pain has not been delineated. While many studies have attributed PAR2-evoked pain to sensory neuron expression, RNA-sequencing experiments are ambiguous on detection of F2rl1 mRNA. Moreover, many pharmacological tools for PAR2 have been shown to be non-specific as they also act on the Mas-related (Mrg) family of g-protein coupled receptors (GPCRs) that are highly enriched in sensory neurons. We sought to bring clarity to the cellular basis of PAR2 pain. We developed a PAR2 conditional mutant mouse by loxp targeting of exon 2 of the F2rl1 gene and specifically deleted PAR2 in all sensory neurons using the PirtCre mouse line. Our behavioral findings show that PAR2 agonist-evoked mechanical hyperalgesia and facial grimacing, but not thermal hyperalgesia, is completely dependent on PAR2 expression in sensory neurons that project to the hindpaw in male and female mice. F2rl1 mRNA is expressed in a discrete population (~4%) of sensory neurons that also express the Nppb and IL31ra genes. This cell population has previously been implicated in itch, but our work shows that PAR2 activation in these cells causes clear pain-related behaviors from the skin. Our findings clarify the mechanism through which proteases, like tryptase and elastase, cause pain via PAR2 activation in a small subset of nociceptors. |
| Databáze: | OpenAIRE |
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