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Functional expression and axonal transport of α7 nAChRs by peptidergic nociceptors of rat dorsal root ganglion

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Abstract

In recent pain studies on animal models, α7 nicotinic acetylcholine receptor (nAChR) agonists demonstrated analgesic, anti-hyperalgesic and anti-inflammatory effects, apparently acting through some peripheral receptors. Assuming possible involvement of α7 nAChRs on nociceptive sensory neurons, we investigated the morphological and neurochemical features of the α7 nAChR-expressing subpopulation of dorsal root ganglion (DRG) neurons and their ability to transport α7 nAChR axonally. In addition, α7 receptor activity and its putative role in pain signal neurotransmitter release were studied. Medium-sized α7 nAChR-expressing neurons prevailed, although the range covered all cell sizes. These cells accounted for one-fifth of total medium and large DRG neurons and <5 % of small ones. 83.2 % of α7 nAChR-expressing DRG neurons were peptidergic nociceptors (CGRP-immunopositive), one half of which had non-myelinated C-fibers and the other half had myelinated Aδ- and likely Aα/β-fibers, whereas 15.2 % were non-peptidergic C-fiber nociceptors binding isolectin B4. All non-peptidergic and a third of peptidergic α7 nAChR-bearing nociceptors expressed TRPV1, a capsaicin-sensitive noxious stimulus transducer. Nerve crush experiments demonstrated that CGRPergic DRG nociceptors axonally transported α7 nAChRs both to the spinal cord and periphery. α7 nAChRs in DRG neurons were functional as their specific agonist PNU282987 evoked calcium rise enhanced by α7-selective positive allosteric modulator PNU120596. However, α7 nAChRs do not modulate neurotransmitter CGRP and glutamate release from DRG neurons since nicotinic ligands affected neither their basal nor provoked levels, showing the necessity of further studies to elucidate the true role of α7 nAChRs in those neurons.

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Acknowledgments

This work was supported by the LOEWE Program of the State of Hessen, Research Focus Non-neuronal cholinergic system, by grants of Russian Foundation for Basic Research No. 13-04-40377-N KOMFI and MCB RAS program. We thank Martin Bodenbenner, Tamara Papadakis, Silke Wiegand and Anna Goldenberg for technical help, Dr. Christina Nassenstein for helpful discussion and Prof. E. Weihe (Philipps-University Marburg) for providing CGRP knockout mice. The authors declare no conflict of interests.

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  1. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Miklukho-Maklaya str., 16/10, 117997, Moscow, Russia

    Irina Shelukhina & Victor Tsetlin

  2. Institute for Anatomy and Cell Biology, Justus-Liebig-University, 35385, Giessen, Germany

    Renate Paddenberg & Wolfgang Kummer

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  1. Irina Shelukhina
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  2. Renate Paddenberg
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  3. Wolfgang Kummer
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  4. Victor Tsetlin
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Correspondence to Irina Shelukhina.

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Shelukhina, I., Paddenberg, R., Kummer, W. et al. Functional expression and axonal transport of α7 nAChRs by peptidergic nociceptors of rat dorsal root ganglion. Brain Struct Funct 220, 1885–1899 (2015). https://doi.org/10.1007/s00429-014-0762-4

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