{"title":"Artemin sensitises mouse (Mus musculus) and naked mole-rat (Heterocephalus glaber) sensory neurons in vitro.","authors":"Lanhui Qiu, Ewan St John Smith","doi":"10.1007/s00359-025-01752-7","DOIUrl":null,"url":null,"abstract":"<p><p>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 in vitro. 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 nociceptive neurons. Using in vitro electrophysiology to record from cultured DRG sensory neurons, we observed that artemin induced depolarization of the resting membrane potential and decreased the rheobase in both species, as well as diminishing the degree of TRPV1 desensitization to multiple capsaicin stimuli. Overall, results indicate that artemin similarly sensitizes sensory neurons in both mice and NMRs, future in vivo studies being required to confirm if the conserved in vitro sensitization also occurs in vivo.</p>","PeriodicalId":54862,"journal":{"name":"Journal of Comparative Physiology A-Neuroethology Sensory Neural and Behavioral Physiology","volume":" ","pages":""},"PeriodicalIF":2.2000,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Comparative Physiology A-Neuroethology Sensory Neural and Behavioral Physiology","FirstCategoryId":"102","ListUrlMain":"https://doi.org/10.1007/s00359-025-01752-7","RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BEHAVIORAL SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
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 in vitro. 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 nociceptive neurons. Using in vitro electrophysiology to record from cultured DRG sensory neurons, we observed that artemin induced depolarization of the resting membrane potential and decreased the rheobase in both species, as well as diminishing the degree of TRPV1 desensitization to multiple capsaicin stimuli. Overall, results indicate that artemin similarly sensitizes sensory neurons in both mice and NMRs, future in vivo studies being required to confirm if the conserved in vitro sensitization also occurs in vivo.
期刊介绍:
The Journal of Comparative Physiology A welcomes original articles, short reviews, and short communications in the following fields:
- Neurobiology and neuroethology
- Sensory physiology and ecology
- Physiological and hormonal basis of behavior
- Communication, orientation, and locomotion
- Functional imaging and neuroanatomy
Contributions should add to our understanding of mechanisms and not be purely descriptive. The level of organization addressed may be organismic, cellular, or molecular.
Colour figures are free in print and online.