Galoyan Samuel M, Petruska Jeffrey C, Mendell Lorne M
Department of Neurobiology and Behavior, State University of New York at Stony Brook, Life Sciences Building, Room 550, Stony Brook, NY 11794-5230, USA.
Eur J Neurosci. 2003 Aug;18(3):535-41. doi: 10.1046/j.1460-9568.2003.02775.x.
We investigated the regulation by nerve growth factor of the response of sensory neurons to noxious heat (>43 degrees C). In dissociated dorsal root ganglion neurons (<30 micro m) from adult rat we demonstrated, using perforated patch clamp recording, that the inward current elicited in response to noxious heating is enhanced by nerve growth factor and reduced by capsazepine. The tachyphylaxis observed in response to the second of two heat pulses was reversed in most cells when nerve growth factor was introduced into the medium during the 5 min between the two heat stimuli, similar to findings using capsaicin [X. Shu & L.M. Mendell (1999) Neurosci. Lett.274, 159-162]. The threshold temperature did not change systematically after nerve growth factor. Using antibodies to TRPV1 and trkA in a subset of cells from which we recorded, we found a virtually perfect correlation between expression of TRPV1 and sensitivity to noxious heat. In addition, trkA expression was perfectly correlated with the ability of nerve growth factor to reverse tachyphylaxis. Thus, this physiological test is a reliable measure of trkA expression in cells sensitive to noxious heat. In agreement with studies in heterologous cells expressing trkA and TRPV1, pharmacologically blocking phospholipase C abolished the effect of nerve growth factor on heat-evoked currents in cells verified to express trkA. We conclude that the response of dorsal root ganglion neurons to noxious heat is conditioned by nerve growth factor in the same way as their response to capsaicin and that these responses require the presence of trkA and TRPV1.
我们研究了神经生长因子对感觉神经元对有害热刺激（>43摄氏度）反应的调节作用。在成年大鼠分离的背根神经节神经元（<30微米）中，我们使用穿孔膜片钳记录法证明，有害热刺激引发的内向电流会被神经生长因子增强，被辣椒素受体拮抗剂降低。在两个热脉冲中的第二个脉冲出现的快速耐受现象，在大多数细胞中，当在两个热刺激之间的5分钟内将神经生长因子加入培养基时会被逆转，这与使用辣椒素的研究结果相似[X. Shu & L.M. Mendell (1999) Neurosci. Lett.274, 159 - 162]。神经生长因子处理后，阈值温度没有系统性变化。在我们记录的一部分细胞中使用针对TRPV1和trkA的抗体，我们发现TRPV1的表达与对有害热的敏感性之间几乎完全相关。此外，trkA的表达与神经生长因子逆转快速耐受的能力完全相关。因此，这种生理学测试是对有害热敏感细胞中trkA表达的可靠测量方法。与在表达trkA和TRPV1的异源细胞中的研究一致，药理学阻断磷脂酶C消除了神经生长因子对经证实表达trkA的细胞中热诱发电流的影响。我们得出结论，背根神经节神经元对有害热的反应与它们对辣椒素的反应一样，受到神经生长因子的调节，并且这些反应需要trkA和TRPV1的存在。
