Electrophysiological properties of neurones with CGRP‐like immunoreactivity in rat dorsal root ganglia

Abstract

Intracellular voltage recordings and fluorescent dye injections were made in vitro in 107 neurons in lumbar dorsal root ganglia (DRGs) of 6- to 8-week-old rats. Calcitonin gene-related, peptide-like immunoreactivity (CGRP-LI) was examined in these neurones, which were divided into C-, A delta-, and A alpha/beta-fibre neurones on the basis of their conduction velocities (CVs). A-fibre neurones with CGRP-LI had significantly longer mean action potential (AP) and afterhyperpolarisation (AHP) durations than those without CGRP-LI. A delta neurones with CGRP-LI had significantly longer AHP durations, slower CVs and slower maximal fibre following frequencies than those without CGRP-LI. They also had longer AP durations (not significant). The largest A delta neurones were CGRP-LI negative, whereas the smaller cells were either positive or negative. A alpha/beta neurones with CGRP-LI also had longer mean APs (not significant) and AHPs (significant) than those without CGRP-LI, and the cell size distributions were similar for positive and negative neurones. Most A-fibre neurones with CGRP-LI had inflections on the falling phase of the somatic AP. Of the A-fibre neurones with such inflections (Ai neurones), those with CGRP-LI had longer AP durations (not significant) and longer AHP durations (significant) than Ai neurones without CGRP-LI, pointing to a functionally distinct subgroup of Ai neurones. There were no significant differences in electrophysiological properties or cell size measurements between C-fibre neurones with and without detectable CGRP-LI. The patterns of electrophysiological properties of A delta neuronal somata with CGRP-LI and of most, but not all, A alpha/beta neuronal somata with CGRP-LI are similar to those reported for cutaneous nociceptors with A fibres in rat (Ritter and Mendell [1992] J. Neurophysiol. 68:2033-2041). Because rat DRG neurones that express CGRP normally also express trkA (Averill et al. [1995] Eur. J. Neurosci. 7:1484-1494), the properties described here of neurones with CGRP-LI are probably the same as those of DRG neurones with trkA.

Quantitative analysis of afferents expressing substance P, calcitonin gene‐related peptide, isolectin B4, neurofilament 200, and Peripherin in the sensory root of the rat trigeminal ganglion

“…The present data suggest that SP and CGRP may be released mostly by unmyelinated C fibers and very rarely by small myelinated Ad fibers in the meninges. We did not see any CGRP1 large myelinated fibers, which conflicts with many electrophysiological studies reporting the existence of CGRP1 neurons with Ab conduction velocity (McCarthy and Lawson, 1990;Lawson et al, 1993Lawson et al, , 1996Lawson et al, , 2002Ruscheweyh et al, 2007). It is possible to assume that some CGRP1 unmyelinated or small myelinated fibers may have Ab conduction velocity.…”

“…It is possible to assume that some CGRP1 unmyelinated or small myelinated fibers may have Ab conduction velocity. This notion can be supported by previous electrophysiological studies showing that some small CGRP1 soma, which would have unmyelinated fibers, have Aa/b conduction velocity (Hoheisel et al, 1994;Lawson et al, 1996). Also, most of the CGRP1 fibers were unmyelinated, although many CGRP1 neurons in the TG were medium or large in size, suggesting…”

“…Similarly, CGRP has been reported to label TG and DRG neurons of all sizes from small to large (McCarthy and Lawson, 1989Lawson, , 1997Ichikawa and Sugimoto, 2002;Ichikawa et al, 2004;Fang et al, 2006). CGRP has also labeled DRG neurons with Aa/b as well as Ad conduction velocity (Lawson et al, , 1996(Lawson et al, , 2002Ruscheweyh et al, 2007), raising the possibility of their expression in large myelinated as well as small myelinated fibers. NF200 also labels some small TG and DRG neurons (Goldstein et al, 1991;Cho et al, 2009) or those with C conduction velocity (Ruscheweyh et al, 2007).…”

Endocannabinoid‐dependent plasticity at spinal nociceptor synapses

“…We therefore performed triple immunofluorescence confocal microscopy on spinal cord sections stained for CB 1 along with substance P (SP) and calcitonin‐gene related peptide (CGRP) to quantify the presence of CB 1 receptors on a subpopulation of peptidergic primary afferent nociceptors. The co‐occurrence of the two neuropeptides unequivocally identifies a subpopulation of peptidergic nociceptive primary afferents (Wiesenfeld‐Hallin et al 1984; Lawson et al 1996). In the superficial dorsal horn of CB 1 fl/fl mice, on average at least 20% of all SP/CGRP double immunopositive axon terminals coexpressed CB 1 receptors.…”

Neutralization of endogenous NGF prevents the sensitization of nociceptors supplying inflamed skin

“…In the adult rat, 40% of sensory neurons in the lumbar dorsal root ganglia express trkA, the high-affinity NGF receptor Averill et al, 1995;Wright & Snider, 1995). These cells have small diameters and contain the neuropeptide calcitonin generelated peptide, suggesting that they have nociceptive functions (Lawson, 1992;Lawson et al, 1996). Administration of exogenous NGF can produce hyperalgesia in rats (Lewin et al, 1992;Della et al, 1994;Woolf et al, 1994;Andreev et al, 1995) and humans (Petty et al, 1994;Dyck et al, 1997), whereas neutralization of endogenous NGF reduces sensitivity to nociceptive stimuli .…”