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

In recent pain studies on animal models, alpha 7 nicotinic acetylcholine receptor (nAChR) agonists demonstrated analgesic, anti-hyperalgesic and anti-inflammatory effects, apparently acting through some peripheral receptors. Assuming possible involvement of alpha 7 nAChRs on nociceptive sensory neurons, we investigated the morphological and neurochemical features of the alpha 7 nAChR-expressing subpopulation of dorsal root ganglion (DRG) neurons and their ability to transport alpha 7 nAChR axonally. In addition, alpha 7 receptor activity and its putative role in pain signal neurotransmitter release were studied. Medium-sized alpha 7 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 alpha 7 nAChR-expressing DRG neurons were peptidergic nociceptors (CGRP-immunopositive), one half of which had non-myelinated C-fibers and the other half had myelinated A delta- and likely A alpha/beta-fibers, whereas 15.2 % were non-peptidergic C-fiber nociceptors binding isolectin B4. All non-peptidergic and a third of peptidergic alpha 7 nAChR-bearing nociceptors expressed TRPV1, a capsaicin-sensitive noxious stimulus transducer. Nerve crush experiments demonstrated that CGRPergic DRG nociceptors axonally transported alpha 7 nAChRs both to the spinal cord and periphery. alpha 7 nAChRs in DRG neurons were functional as their specific agonist PNU282987 evoked calcium rise enhanced by alpha 7-selective positive allosteric modulator PNU120596. However, alpha 7 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 alpha 7 nAChRs in those neurons.