Cells in Laminae III and IV of the Rat Spinal Cord that Possess the Neurokinin-1 Receptor and Have Dorsally Directed Dendrites Receive a Major Synaptic Input from Tachykinin-Containing Primary Afferents

Naim, Magda Mohamed; Spike, Rosemary C.; Watt, Christine; Shehab, Safa; Todd, Andrew J.

doi:10.1523/jneurosci.17-14-05536.1997

Cited by 131 publications

(150 citation statements)

References 34 publications

(49 reference statements)

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“…Therefore, these results using immunocytochemistry do not favor a direct synaptic association between SP-containing afferents and neurons expressing the NK-1r. A confocal microscopic study adds to the controversy by showing that NK-1r immunoreactive neurons with cell bodies in laminae III-IV received a substantially higher number of appositions from SP immunoreactive boutons than neurons that expressed choline acetyltransferase but that were not NK-1r immunoreactive (11). This latter observation, together with our own results showing a preferential innervation by SP of nociceptive neurons (12), has led us to believe that SP in the spinal cord might not act in a diffuse manner as had been suggested (8) but, rather, that it might activate the NK-1r at a short distance from its site of release.…”

mentioning

confidence: 99%

Preferential synaptic relationships between substance P-immunoreactive boutons and neurokinin 1 receptor sites in the rat spinal cord

McLeod

Krause

Cuello

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

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Substance P plays an important role in the transmission of pain-related information in the dorsal horn of the spinal cord. Recent immunocytochemical studies have shown a mismatch between the distribution of substance P and its receptor in the superficial laminae of the dorsal horn. Because such a mismatch was not observed by using classical radioligand binding studies, we decided to investigate further the issue of the relationship between substance P and its receptor by using an antibody raised against a portion of the carboxyl terminal of the neurokinin 1 receptor and a bispecific monoclonal antibodies against substance P and horseradish peroxidase. Light microscopy revealed a good correlation between the distributions of substance P and the neurokinin 1 receptor, both being localized with highest densities in lamina I and outer lamina II of the spinal dorsal horn. An ultrastructural double-labeling study, combining preembedding immunogold with enzyme-based immunocytochemistry, showed that most neurokinin 1 receptor immunoreactive dendrites were apposed by substance P containing boutons. A detailed quantitative analysis revealed that neurokinin 1 receptor immunoreactive dendrites received more appositions and synapses from substance P immunoreactive terminals than those not expressing the neurokinin 1 receptor. Such preferential innervation by substance P occurred in all superficial dorsal horn laminae even though neurokinin 1 receptor immunoreactive dendrites were a minority of the total number of dendritic profiles in the above laminae. These results suggest that, contrary to the belief that neuropeptides act in a diffuse manner at a considerable distance from their sites of release, substance P should act on profiles expressing the neurokinin 1 receptor at a short distance from its site of release.Substance P (SP) is a neuropeptide prominently expressed in small sensory primary afferents that is involved in the modulation of pain-related information in the spinal dorsal horn (1, 2). The central terminations of SP-containing primary sensory afferents occur mainly in laminae I and II (3, 4). There is abundant evidence supporting the notion that SP acts preferentially on the neurokinin 1 receptor (NK-1r) (5). The distribution of the NK-1r in the spinal cord has been studied extensively by using radioactive ligand binding and, more recently, immunocytochemistry. The former approach has shown a close match between the distribution of SP immunoreactivity and NK-1r binding sites in the superficial laminae of the dorsal horn (6, 7). In contrast, studies using two different antibodies against the NK-1r have shown a conspicuous lack of NK-1r immunostaining in lamina II (8-10), an area that is abundantly innervated by SP. Therefore, these results using immunocytochemistry do not favor a direct synaptic association between SP-containing afferents and neurons expressing the NK-1r. A confocal microscopic study adds to the controversy by showing that NK-1r immunoreactive neurons with cell bodies in laminae III-IV ...

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mentioning

confidence: 99%

Preferential synaptic relationships between substance P-immunoreactive boutons and neurokinin 1 receptor sites in the rat spinal cord

McLeod

Krause

Cuello

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

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“…CGRP has been postulated as a useful marker for primary afferent terminals (37) due to its fast disappearance after rhizotomy and its absence from neuronal bodies or axon terminals of intrinsic dorsal horn neurons (37)(38)(39). CGRP-positive afferents are present in laminae I and II of the dorsal horn (22,26,36,37,40). Unilateral dorsal rhizotomy of nine consecutive segments of the cervico-thoracic spinal cord caused a significant, though incomplete loss of CGRP-immunoreactive fibers in the spinal cord ipsilateral to the rhizotomy.…”

Section: Discussionmentioning

confidence: 99%

“…The small C fiber DRG cells have been classified on the basis of their function and phenotype (20) into two groups: peptidergic and non-peptidergic. The C fibers that express neuromodulatory peptides (e.g., substance P; SP, calcitonin gene related peptide, CGRP) project to lamina I and lamina II outer of the dorsal horn (21)(22)(23). Many of these peptidergic fibers also express the p75 neurotrophin receptor (24).…”

Section: Degeneración De Los Terminales Aferentes Primarios De Rata Lmentioning

confidence: 99%

Degeneración de los terminales aferentes primarios de rata luego de lesión extensa por avulsión del plexo braquial

et al. 2004

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Important breakthroughs in the understanding regeneration failure in an injured CNS have been made by studies of primary afferent neurons. Dorsal rhizotomy has provided an experimental model of brachial plexus (BP) avulsion. This is an injury in which the central branches of primary afferents are disrupted at their point of entry into the spinal cord, bringing motor and sensory dysfunction to the upper limbs. In the present work, the central axonal organization of primary afferents was examined in control (without lesion) adult Wistar rats and in rats subjected to a C3-T3 rhizotomy. Specific sensory axon subtypes were recognized by application of antibodies to the calcitonin gene-related peptide (CGRP), the P2X3 purinoreceptor, the low-affinity p75-neurotrophin receptor and the retrograde tracer cholera toxin subunit β (TCβ). Other subtypes weres labeled with the lectin Griffonia simplicifolia IB4. Using immunohistochemistry and high resolution light microscopy, brachial plexus rhizotomy in adult rats has proven a reliable model for several neural deficits in humans. This lesion produced different degrees of terminal degeneration in the several types of primary afferents which define sub-populations of sensitive neurons. Between the C6 and C8 levels of the spinal cord,, deafferentation was partial for peptidergic GCRP-positive fibers, in contrast with elimination of non peptidergic and myelinated fibers. Dorsal rhizotomy has provided an adequate experimental model to study sensory alterations such as acute pain and allodynia as well as factors that affect regeneration into the CNS., Therefore, the differential deafferentation response must be considered inr the evaluation of therapies for nociception (pain) and regeneration for brachial plexus avulsion. The anatomical diffierences among the primary afferent subtypes also affect their roles in normal and damaged conditions. Key words: primary afferents, cervical spinal cord, dorsal root avulsion, lectin Griffonia simplicifolia (IB4), cholera toxin subunit b (CTβ), calcitonin gene-related peptide (CGRP), purinoreceptor (P2X3). Degeneración de los terminales aferentes primarios de rata luego de lesión extensa por avulsión del plexo braquialEl uso de las neuronas sensoriales primarias ha aportado avances en el entendimiento de las razones por las cuales falla la regeneración cuando el sistema nervioso central (SNC) es dañado. La rizotomía dorsal se puede usar como un modelo experimental de las lesiones por avulsión del plexo braquial, una lesión en la cual son desprendidas, en su punto de entrada en la médula espinal, las ramas centrales de los aferentes primarios causando una disfunción motora y sensorial grave e irreversible del miembro superior. En el presente trabajo, se examinó la organización central de los aferentes primarios en ratas Wistar adultas. Éstas fueron divididas en controles normales no lesionados y en animales rizotomizados entre los niveles cervical 3 y torácico 3 (C3-T3). Se estudió la deaferentación de los subtipos de axones sensoriales utiliza...

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“…This was confirmed in electron microscopic studies that also showed that there is a significant mismatch between the presence of SP terminals and the NK-1 receptor; the latter had a much more extensive distribution (34), suggestive of extrasynaptic transmission (35,36, but see 37). In fact, despite the presence of dense SP immunoreactivity in lamina II (the substantia gelatinosa), the only element that expresses the NK-1 receptor in this region corresponds to the dorsally directed dendrites of large NK-1 receptor-expressing neurons in lamina III (38,39).…”

Section: Internalization Of Nk-1 Receptormentioning

confidence: 98%

Presynaptic control of nociceptor signalling: Differential influence of Mu Opioid and GABAergic Systems

Riley

Trafton

Basbaum

2000

Pain Research and Management

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It is difficult to pick a topic to discuss that adequately honours Ron Melzack's many years of pain research. This is particularly problematic if one is cognizant of the tremendous emphasis that Ron puts on the distinction between pain and nociception. Indeed, the thread that binds so many of Ron's studies is that the complexity of the pain experience will not be understood if one exclusively concentrates on the processing of nociceptive messages at the level of the periphery or spinal cord. Ron always emphasized the importance of affective and cognitive components of the pain experience. These elements of the pain experience, so beautifully and memorably discussed in Melzack and Casey's (1) theoretical review, must always be included when this topic is addressed. Dr Allan Basbaum was a student of Ron's in an undergradu- The relative contribution of pre-and postsynaptic controls to the flow of nociceptive information at the level of the spinal cord has been one of Ron Melzack's longstanding interests and a key issue in the formulation of the gate control theory. The authors review their own studies, in which they monitored internalization of the neurokinin-1 receptor to examine specifically the action of two classically inhibitory systems -mu opioid and gamma-amino butyric acid (GABA) -on noxious stimulus-evoked tachykinin signalling in the rat spinal cord. Evidence that opioids and GABAergic controls operate differently on the central consequences of any noxious stimulus-induced substance P release is provided. Whereas at least 80% of the tachykinin signalling remained intact after even the highest concentration of spinal morphine or D-Ala2, NMe-phe4, Glyol5-enkephalin administration, spinal administration of the GABA B receptor agonist baclofen had a dramatic inhibitory effect. These findings are discussed in light of the disappointing clinical utility of baclofen and neurokinin-1 receptor antagonists to combat pain. Key Words: Gamma-amino butyric acid; Mu opioid; Neurokinin 1 receptors; Receptor internalization; Spinal cord; TachykininsCommande présynaptique de la transmission des signaux par les nocicepteurs : mécanisme d'action des opioïdes de type mu et du GABA Le rôle relatif des commandes pré-et postsynaptiques dans la transmission des signaux nociceptifs dans la moelle épinière, en plus de susciter l'intérêt soutenu de Ron Melzack, a constitué un pilier de la théorie du ‹‹ portillon ››. Les auteurs ont passé en revue leurs propres études dans lesquelles ils se sont penchés sur l'endocytose des récep-teurs de la neurokinine 1 afin d'étudier le mécanisme d'action de deux inhibiteurs classiques, les opioïdes de type mu et l'acide gammaaminobutyrique (GABA), sur la transmission de la tachykinine déclen-chée par un stimulus nocif dans la moelle épinière du rat. Ils ont recueilli des preuves selon lesquelles les opioïdes et le GABA agissent différemment sur les effets centraux de la libération de la substance P, provoquée par un stimulus nocif. Tandis qu'au moins 80 % de la transmission des signaux par la tac...

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Cells in Laminae III and IV of the Rat Spinal Cord that Possess the Neurokinin-1 Receptor and Have Dorsally Directed Dendrites Receive a Major Synaptic Input from Tachykinin-Containing Primary Afferents

Cited by 131 publications

References 34 publications

Preferential synaptic relationships between substance P-immunoreactive boutons and neurokinin 1 receptor sites in the rat spinal cord

Preferential synaptic relationships between substance P-immunoreactive boutons and neurokinin 1 receptor sites in the rat spinal cord

Degeneración de los terminales aferentes primarios de rata luego de lesión extensa por avulsión del plexo braquial

Presynaptic control of nociceptor signalling: Differential influence of Mu Opioid and GABAergic Systems

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