4.4 Article

Nicotine Evoked Currents in Human Primary Sensory Neurons

期刊

JOURNAL OF PAIN
卷 20, 期 7, 页码 810-818

出版社

CHURCHILL LIVINGSTONE
DOI: 10.1016/j.jpain.2019.01.005

关键词

Patch clamp; nociceptor; chemosensitive; ionotropic; in vitro

资金

  1. National Institutes of Health [R01NS083347, R01 DK107966]
  2. National Natural Science Funds of China [81670686]
  3. Shandong Natural Science Funds [ZR2015HM001]
  4. Eli Lilly Co.

向作者/读者索取更多资源

Sensory neuron nicotinic acetylcholine receptors (nAChRs) contribute to pain associated with tissue injury. However, there are marked differences between rats and mice with respect to both the properties and distribution of nAChR currents in sensory neurons. Because both species are used to understand pain signaling in humans, we sought to determine whether the currents present in either species was reflective of those present in human sensory neurons. Neurons from the L4/L5 dorsal root ganglia were obtained from adult male and female organ donors. Nicotine evoked currents were detected in 40 of 47 neurons (85%). In contrast with the naive mouse, in which almost all nAChR currents are transient, or the rat, in which both mouse-like transient and more slowly activating and inactivating currents are detected, all the currents in human DRG neurons were slow, but slower than those in the rat. Currents were blocked by the nAChR antagonists mecamylamine (30 mu mol/L), but not by the TRPA1 selective antagonist HC-030031 (10 mu mol/L). Single cell polymerase chain reaction analysis of nicotinic receptor subunit expression in human DRG neurons are consistent with functional data indicating that receptor expression is detected 85 +/- 2.1% of neurons assessed (n = 48, from 4 donors). The most prevalent coexpression pattern was alpha 3/beta 2 (95 +/- 4% of neurons with subunits), but alpha 7 subunits were detected in 70 +/- 3.4% of neurons. These results suggest that there are not only species differences in the sensory neuron distribution of nAChR currents between rodent and human, but that the subunit composition of the channel underlying human nAChR currents may be different from those in the mouse or rat. Perspective: The properties and distribution of nicotine evoked currents in human sensory neurons were markedly different from those previously observed in mice and rats. These observations add additional support to the suggestion that human sensory neurons may be an essential screening tool for those considering moving novel therapeutics targeting primary afferents into clinical trials. (C) 2019 by the American Pain Society

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