Qiu Lanhui, Smith Ewan St John
Department of Pharmacology, University of Cambridge, Cambridge, UK.
J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2025 Jul 24. doi: 10.1007/s00359-025-01752-7.
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.
裸鼹鼠（NMR，Heterocephalus glaber）是一种地下啮齿动物，具有一系列不寻常的生理特征，包括炎症性疼痛减弱。例如，神经生长因子（NGF）作为一种关键的炎症介质，无法在裸鼹鼠中诱导感觉神经元致敏和热痛觉过敏。NGF诱导的神经元致敏和热痛觉过敏的缺失是由于NGF受体原肌球蛋白受体激酶A（TrkA）的信号功能低下所致。与NGF-TrkA信号传导一样，神经营养因子Artemin是胶质细胞源性神经营养因子（GDNF）家族的成员，通过其受体GDNF家族受体α3（GFRα3）参与介导炎症性疼痛，该受体由背根神经节（DRG）感觉神经元的一个亚群表达。在这里，我们研究了小鼠和裸鼹鼠DRG神经元中GFRα3的表达，并在体外测量了Artemin对这两个物种DRG感觉神经元功能的影响。通过免疫组织化学，我们观察到小鼠和裸鼹鼠DRG感觉神经元中GFRα3的丰度相似，与瞬时受体电位香草酸受体1（TRPV1）离子通道高度共表达，表明这些神经元是伤害性神经元。利用体外电生理学记录培养的DRG感觉神经元，我们观察到Artemin在两个物种中均诱导静息膜电位去极化并降低阈强度，同时减少TRPV1对多种辣椒素刺激的脱敏程度。总体而言，结果表明Artemin在小鼠和裸鼹鼠中同样使感觉神经元致敏，未来需要进行体内研究以确认体外保守的致敏作用在体内是否也会发生。
