Artemin sensitises mouse ( Mus musculus ) and naked mole-rat ( Heterocephalus glaber ) sensory neurons

The naked mole-rat (NMR, Heterocephalus glaber ) is a subterranean rodent that exhibits a range of unusual physiological traits, including diminished inflammatory pain. For example, nerve growth factor (NGF), a key inflammatory mediator, fails to induce sensitization of sensory neurons and thermal hyperalgesia in NMRs. This lack of NGF-induced neuronal sensitization and thermal hyperalgesia results from hypofunctional signaling of the NGF receptor, tropomyosin receptor kinase A (TrkA). Like NGF-TrkA signaling, the neurotrophic factor artemin, a member of the glial cell line-derived neurotrophic factor (GDNF) family, is implicated in mediating inflammatory pain through its receptor, GDNF family receptor α3 (GFRα3), which is expressed by a subset of dorsal root ganglia (DRG) sensory neurons. Here we investigated GFRα3 expression in DRG neurons of mice and NMRs, as well as measuring the impact of artemin on DRG sensory neuron function in both species. Using immunohistochemistry, we observed a similar abundance of GFRα3 in mouse and NMR DRG sensory neurons, high coexpression with the transient receptor potential vanilloid 1 (TRPV1) ion channel suggesting that these neurons are nociceptors. Using electrophysiology, we observed that artemin induced depolarization of the resting membrane potential and decreased the rheobase of sensory neurons in both species, as well as diminishing the degree of TRPV1 desensitization to multiple capsaicin stimuli. Overall, results indicate that artemin sensitizes sensory neurons in both mice and NMRs, suggesting a conserved mechanism of sensory modulation.