Co‐localization of nociceptive markers in the lumbar dorsal root ganglion and spinal cord of dromedary camel

Abstract

Nociceptive markers in mice have been identified in two distinct peptidergic and nonpeptidergic neurons in the dorsal root ganglion (DRG) and distributed in different laminae of the dorsal horn of the spinal cord. Recently, however, a study in humans showed a significant overlapping in these two populations. In this study, we investigated the distribution of various nociceptive markers in the lumbar DRG and spinal cord of the dromedary camel. Immunohistochemical data showed a remarkable percentage of total neurons in the DRG expressed IB4 binding (54.5%), calcitonin gene-related peptide (CGRP; 49.5%), transient receptor potential vanilloid 1 (TRPV1; 48.2%), and nitric oxide synthase (NOS; 30.6%). The co-localization data showed that 89.6% and 74.0% of CGRP-and TRPV1-labeled neurons, respectively, were IB4 positive. In addition, 61.6% and 84.2% of TRPV1-and NOS-immunoreactive neurons, respectively, were also colocalized with CGRP. The distribution of IB4, CGRP, TRPV1, substance P, and NOS immunoreactivities in the spinal cord were observed in lamina I and outer lamina II (IIo). Quantitative data showed that 82.4% of IB4-positive nerve terminals in laminae I and IIo were co-localized with CGRP, and 86.0% of CGRP-labeled terminals were colocalized with IB4. Similarly, 85.1% of NOS-labeled nerve terminals were co-localized with CGRP. No neuropeptide Y (NPY) or cholecystokinin (CCK) immunoreactivities were detected in the DRG, and no co-localization between IB4, NPY, and CCK were observed in the spinal cord. Our results demonstrate marked convergence of nociceptive markers in the primary afferent neurons in camels, which is similar to humans rather than the mouse. The data also emphasizes the importance of interspecies differences when selecting ideal animal models for studying nociception and treating chronic pain.

Distribution and Chemistry of Phoenixin-14, a Newly Discovered Sensory Transmission Molecule in Porcine Afferent Neurons

“…In the present study, PNX + /nNOS-containing neurons formed the third largest (approximately 50%) population among all afferent cells capable of synthesizing and releasing PNX as their transmitter; the vast majority of these neurons were Sl-and M-sized cells. This is well in line with the data obtained in other species (humans, rats, mice, sheep, dromedary camels [20,[51][52][53]) where nitrergic afferent neurons were found in an average of 40-50% of all DRG cells, with the highest percentage in the subpopulation of Sl-and M-sized neurons. It should be emphasized that the high degree of nNOS co-localization with SP and CGRP, reported by Russo and colleagues [53], additionally supports the above hypothesis, suggesting the existence of a PNX + /SP + /CGRP + /NOS + population of DRG cells.…”

“…Previous studies revealed that, CGRP, together with SP (see below), appears to be the "canonical" transmission molecule of afferent neurons in all mammalian species studied so far (human, horse, dromedary camel, pig, cat, rat and mouse) [16][17][18][19][20]. According to the available data, the proportion of sensory neurons containing CGRP (or expressing mRNA encoding this peptide [21,22]) ranging, on average, between 50 and 60% of all DRG cells, regardless of the species studied.…”

“…The above-mentioned close interdependence and cooperation of CGRP and SP in numerous regulatory loops seem to result from the fact that both substances coexist very often in the same sensor cell [14,17,20] from which they are released together and synergistically interact with target cells, supporting each other. For example, as revealed by Biella and co-workers [32], the excitatory effects of SP arising from spontaneous and noxious activity were significantly enhanced by CGRP in rats.…”

Distribution and Chemistry of Phoenixin-14, a Newly Discovered Sensory Transmission Molecule in Porcine Afferent Neurons

“…As shown in previous studies, CGRP appears to be, together with SP (see below), the "canonical" transmission molecule of afferent neurons in all mammalian species studied so far (human, horse, dromedary camel, pig, cat, rat and mouse) [19][20][21][22][23]. According to the available data, the number of sensory neurons containing CGRP (or expressing mRNA encoding this peptide [24,25]) oscillates on average between 50 and 60% of all DRG cells, regardless of the species studied.…”

“…The above-mentioned close interdependence and cooperation of CGRP and SP in numerous regulatory loops seems to result from the fact that both substances coexist very often in the same sensory cell [17,20,23] from which they are released together and interact with target cells in a synergistic way, supporting each other. For example, as revealed by Biella and co-workers [35], the excitatory effects of SP arising from spontaneous and noxious activity were significantly enhanced by CGRP in the rat.…”