Differences in the chemical expression of rat primary afferent neurons which innervate skin, muscle or joint

O’Brien, Claire; Woolf, C. J.; Fitzgerald, Maria; Lindsay, Ronald M.; Molander, Carl

doi:10.1016/0306-4522(89)90096-1

Cited by 162 publications

(74 citation statements)

References 33 publications

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“…The fraction of our neurones with positive SP_LI (> 20 % absorbance) was 25% of the total sample; this included nearly 40% of the C fibre and 15% of A fibre cells tested. We found 22% of cutaneous afferent neurones to exhibit SP_LI, a value similar to that reported for cutaneous afferent DRG neurones in rat (18-28%;O'Brien, Woolf, Fitzgerald, Lindsay & Molander, 1989;Lawson, 1992). These comparable numbers lend circumstantial support to our labelling and adequacy of sampling.…”

Section: Discussionsupporting

confidence: 71%

Relationship of substance P to afferent characteristics of dorsal root ganglion neurones in guinea‐pig

Lawson¹,

Crepps

Perl

1997

The Journal of Physiology

243

193

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The relationship between the afferent properties and substance P‐like immunoreactivity (SP‐LI) of L6 and SI dorsal root ganglion (DRG) neuronal somata was examined in anaesthetized guinea‐pigs. Glass pipette microelectrodes filled with fluorescent dyes were used to make intracellular recordings and to label DRG somata. The dorsal root conduction velocity (CV) and the afferent receptive properties of each unit were categorized according to criteria established in other species. Categories included a variety of low threshold mechanoreceptive classes, innocuous thermoreceptive and several nociceptive classes. Nociceptive units were further subdivided on the basis of CV and the locus of the receptive field (superficial cutaneous, deep cutaneous or subcutaneous). SP‐LI was determined using the avidin–biotin complex method and the relative staining intensity determined by image analysis. The possible significance of labelling intensity is discussed. Clear SP‐LI appeared in twenty‐nine of 117 dye‐labelled neurones. All SP‐LI positive units with identified receptive properties were nociceptive but not all categories of nociceptors were positive. The intensity of SP‐LI labelling varied, often systematically, in relation to afferent properties. There was a tendency for nociceptive neurones with slower CVs and/or smaller cell bodies to show SP‐LI. Nineteen of fifty‐one C fibre neurones showed SP‐LI. Fewer than half the C polymodal nociceptors (CPMs) were positive. The most intensely labelled units were the deep cutaneous nociceptors and some of the CPMs in glabrous skin. C low threshold mechanoreceptors and cooling‐sensitive units did not show SP‐LI. Ten of sixty‐six A fibre neurones exhibited SP‐LI, including eight of sixteen Aδ nociceptors and two of fifteen Aα/β nociceptors. A fibre neurones exhibiting SP‐LI included seven of eight deep cutaneous mechanical nociceptors and some superficial cutaneous mechano‐heat nociceptors of hairy skin. In contrast, none of twenty superficial cutaneous A high threshold mechanoreceptor units or the thirty‐five A fibre low threshold units (D‐hair and other units) showed detectable SP‐LI. We conclude that SP‐LI labelling in guinea‐pig DRG neurones is related to (a) afferent receptive properties, (b) the tissue in which the peripheral receptive terminals are located, (c) the CV and (d) the soma size.

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Section: Discussionsupporting

confidence: 71%

Relationship of substance P to afferent characteristics of dorsal root ganglion neurones in guinea‐pig

Lawson¹,

Crepps

Perl

1997

The Journal of Physiology

243

193

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“…For example, neuropeptides, including calcitonin gene-related peptide (CGRP), often are found in small-sized neurons that constitute approximately one-third of the dorsal root ganglion (DRG) and that can innervate skin and viscera (Lee et al, 1985;Gibbins et al, 1987;Molander et al, 1987;O'Brien et al, 1989;McCarthy and Lawson, 1990;Noguchi et al, 1990;Kashiba et al, 1991). CGRP is localized in polymodal nociceptors and is a potent vasodilator (Brain et al, 1985;Wallengren and Hakanson, 1987;Holzer, 1988;Scott, 1992).…”

Section: Abstract: Sensory Ganglion; Calcitonin Gene-related Peptidementioning

confidence: 99%

Depolarization Stimulates Initial Calcitonin Gene-Related Peptide Expression by Embryonic Sensory NeuronsIn Vitro

MacPhedran

Hall

1998

J. Neurosci.

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The neuropeptide calcitonin gene-related peptide (CGRP) is expressed by one-third of adult rat lumbar dorsal root ganglion (DRG) neurons, many of which mediate pain sensation or cause vasodilation. The factors that regulate the developmental expression of CGRP are poorly understood. Embryonic DRG neurons initially lack CGRP. When these neurons were stimulated in culture by serum or persistent 50 mM KCl application, the same percentage of CGRP-immunoreactive (CGRP-IR) neurons developed in vitro as was seen in the adult DRG in vivo. The addition of the L-type calcium channel blockers, 5 M nifedipine or 10 M verapamil, dramatically decreased the proportion of CGRP-IR neurons that developed, although the N-type calcium channel blocker, 2.5 M -conotoxin, was less effective. By contrast, the sodium channel blocker 1 M tetrodotoxin had no effect on CGRP expression after depolarization. Fura-2 ratiometric imaging demonstrated that mean intracellular free calcium levels increased from 70 to 135 nM with chronic depolarization, and the addition of nifedipine inhibited that increase. Only a subpopulation of neurons had elevated calcium concentrations during chronic depolarization, and they were correlated with CGRP expression. Key signal transduction pathways were tested pharmacologically for their role in CGRP expression after depolarization; the addition of the CaM kinase inhibitor KN-62 reduced the proportion of CGRP-IR neurons to basal levels. By contrast, protein kinase A and protein kinase C were not implicated in the depolarization-induced CGRP increases. These data suggest that depolarization and the subsequent Ca 2ϩ -based signal transduction mechanisms play important roles in the de novo expression of CGRP by specific embryonic DRG neurons.

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“…Neuropeptides are often found in small DRG neurons that can innervate skin and viscera, whereas abundant neurofilament expression is characteristic of large neurons that innervate muscle spindles (Lawson et al, 1984;Perry et al, 1991). The neuropeptides CGRP and substance P are usually found in small neurons but can be contained in sensory neurons of varied sizes (Gibson et al, 1984;Lee et al, 1985;Skofitsch and Jacobowitz, 1985;Gibbins et al, 1987;Marti et al, 1987;Molander et al, 1987;Lawson, 1989, 1990;O'Brien et al, 1989). The coexistence of particular peptides in specific subpopulations of DRG neurons is related to peripheral targets.…”

mentioning

confidence: 99%

The Generation of Neuronal Heterogeneity in a Rat Sensory Ganglion

Hall

Hickman

et al. 1997

J. Neurosci.

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Adult sensory neurons differ chemically, morphologically, and functionally, but the factors that generate their diversity remain unclear. For example, neuropeptides are generally found in small neurons, whereas abundant neurofilament is common in large neurons. Neurons containing the neuropeptides calcitonin gene-related peptide (CGRP) or substance P were quantified using immunohistochemistry in rat lumbar dorsal root ganglion (DRG) at times before and after sensory neurons contact central and peripheral targets in vivo. No neurons in the newly formed DRG expressed neuropeptide or neuropeptide mRNA, but neuropeptides were detectable about the time that axons connect with peripheral targets. To determine the requirement for target in neuropeptide regulation, embryonic DRG neurons were isolated at times before central and peripheral connections had formed, placed in culture, and immunocytochemically assayed for CGRP and substance P. Cultured neurons expressed neuropeptides with a time course and in proportions similar to those in vivo. Thus, some neurons in the embryonic DRG seem to be intrinsically specified to later express CGRP and substance P. The percentage of CGRP-immunoreactive neurons was not changed by cell density, non-neuronal cells, neurotrophins in addition to nerve growth factor (NGF), or antibody inactivation of neurotrophin-3 in the presence of NGF. To test the role of extrinsic cues on CGRP expression, DRG neurons were co-cultured with potential target tissues. Coculture with a rat epidermal or smooth muscle cell line increased the proportion of CGRP-containing neurons, whereas primary skeletal muscle and 3T3 cells had no effects. Thus, multiple appropriate sensory neuron phenotypes arise in a regulated fashion in cultured neurons isolated before target connections have formed, and some candidate target tissues can modulate that intrinsic expression pattern. Key words: neuropeptides; substance P; calcitonin generelated peptide; neurofilament; nociceptive; sensory ganglion; target tissue; skin; neurotrophinA striking feature of the adult vertebrate sensory nervous system is the diversity of neuronal cell types that perform together to maintain homeostasis and convey information about the environment. During development, specific neurons must be generated in appropriate locations and connect discretely to both peripheral targets and the CNS for functional integrity. Thus, it is important to understand not only how the phenotype is generated but also how neurons match targets. This study examines the developmental regulation of sensory neurons containing calcitonin generelated peptide (CGRP) that predominantly contact visceral and cutaneous peripheral target end organs in vivo.Adult rat sensory neurons can express neuromodulatory neuropeptides, but the factors that regulate their initial expression remain unknown. Cutaneous afferents appear in rat proximal hindlimb on embryonic days 14 -15 (E14 -E15) and in skin of distal toes at E16 -E17 (Reynolds et al

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Differences in the chemical expression of rat primary afferent neurons which innervate skin, muscle or joint

Cited by 162 publications

References 33 publications

Relationship of substance P to afferent characteristics of dorsal root ganglion neurones in guinea‐pig

Relationship of substance P to afferent characteristics of dorsal root ganglion neurones in guinea‐pig

Depolarization Stimulates Initial Calcitonin Gene-Related Peptide Expression by Embryonic Sensory NeuronsIn Vitro

The Generation of Neuronal Heterogeneity in a Rat Sensory Ganglion

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