Selective innervation of NK1 receptor–lacking lamina I spinoparabrachial neurons by presumed nonpeptidergic Aδ nociceptors in the rat

Baseer, Najma; Al-Baloushi, Abdullah; Watanabe, Masahiko; Shehab, Safa; Todd, Andrew J.

doi:10.1016/j.pain.2014.08.023

Cited by 9 publications

(14 citation statements)

References 71 publications

(141 reference statements)

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“…Sixteen neurons (n=8 sham and n=8 pSNL) from 22 different animals were identified and met criteria to be classified as AHTMR consistent with our previous reports [24,25,29]. In these neurons the center of the RF was used for response testing to the apex of the pyramids within the RF (Fig.…”

Section: Resultsmentioning

confidence: 90%

“…Previous studies have not been able to demonstrate that LTMR activation produces pain as measured by place aversion and this may be because the hyperalgesia is related to the higher threshold mechanical nociceptive units and their activation of second order neurons in nociceptive lamina [9,29–31]. Nevertheless, activation of LTMR tactile units may have an impact as surfaces produce a unique and different sensation.…”

Section: Discussionmentioning

confidence: 99%

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Nerve injury induced activation of fast-conducting high threshold mechanoreceptors predicts non-reflexive pain related behavior

Boada

Martin

Ririe

2016

Neuroscience Letters

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The role of specific subsets of peripheral nerves in pain related behavior remains unclear. To better understand the contribution of differential activation of fast-conducting, high-threshold mechanoreceptor (AHTMR) input, we hypothesized that neuronal activation would be distinct with nerve injury, and that nociceptive input would predictt behavior in the freely exploring animal. A series of surfaces was used to deliver mechanical input to the hindpaws of rats upon voluntary movement and exploration. Neuronal activation increased as apex surface decreased (0.2, 0.6, 1.0 and 1.5 mm) using in vivo recording in L4 DRG neurons, and this relationship was enhanced following partial ligation of L5 (pSNL). In behaving animals, apex size was correlated to time spent on each surface following pSNL, but not with sham. Morphine normalized the discriminatory behavior following pSNL. These data indicate that noxious mechanical activation of AHTMR upon normal movement predicts behavior using paradigms that do not rely on reflexive withdrawal responses suggesting that AHTMR activation and central nervous system input contribute to higher order pain behavior after nerve injury beyond the immediate early pain input long attributed to these neurons.

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Section: Resultsmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Nerve injury induced activation of fast-conducting high threshold mechanoreceptors predicts non-reflexive pain related behavior

Boada

Martin

Ririe

2016

Neuroscience Letters

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“…Further investigations from our group will focus on the representation of corneal afferent fibers in a cleared brain using a mixture of tracers that discriminate between myelinated and unmyelinated fibers. It is well known that each fiber type projects preferentially to different laminae of the dorsal horns of the medulla and spinal cord; CTB mainly labels terminals in laminae I and IIIeV, but not in lamina II (Baseer et al, 2014;Shehab and Hughes, 2011). The full range of ocular surface afferents has been previously described from animals whose corneas were treated with a mixture of HRP-CTB and HRP-WGA, using classical histological methods (Panneton et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Combined 3DISCO clearing method, retrograde tracer and ultramicroscopy to map corneal neurons in a whole adult mouse trigeminal ganglion

Launay

Godefroy

Khabou

et al. 2015

Experimental Eye Research

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Tissue clearing and subsequent imaging of intact transparent tissues have provided an innovative way to analyze anatomical pathways in the nervous system. In this study, we combined a recent 3-dimensional imaging of solvent cleared organ (3DISCO) procedure, light-sheet microscopy, fluorescent retrograde tracer, and Imaris software to 3D map corneal sensory neurons within a whole adult mouse trigeminal ganglion (TG). We first established the optimized steps to easily and rapidly clear a fixed TG. We found that the 3DISCO procedure gave excellent results and took less than 3 h to clear the TG. In a second set of experiments, a retrograde tracer (cholera toxin B Alexa 594-conjugated) was applied to de-epithelialized cornea to retrograde-labeled corneal sensory neurons. Two days later, TGs were cleared by the 3DISCO method and serial imaging was performed using light-sheet ultramicroscopic technology. High-resolution images of labeled neurons can be easily and rapidly obtained from a 3D reconstructed whole mouse TG. We then provided a 3D reconstruction of corneal afferent neurons and analyzed their precise localization in the TG. Thus, we showed that neurons supplying corneal sensory innervation exhibit a highly specific limited dorsomedial localization within the TG. We report that our combined method offers the possibility to perform manual (on 20 μm sections) and automated (on 3D reconstructed TG) counting of labeled cells in a cleared mouse TG. To conclude, we illustrate that the combination of the 3DISCO clearing method with light-sheet microscopy, retrograde tracer, and automatic counting represents a rapid and reliable method to analyze a subpopulation of neurons within the peripheral and central nervous system.

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“…Myelinated nociceptive Ad fibers are known to project into superficial lamina I and deeper lamina V whereas mechanoreceptive Ad fibers are mostly distributed in laminae III-V (Light & Perl, 1979;Robertson & Grant, 1985). Several previous reports showed myelinated A fibers presumed to be nociceptive Ad fibers at the marginal dorsal horn (lamina I) with CTB injections into the sciatic nerve (Baseer, Al-Baloushi, Watanabe, Shehab, & Todd, 2014;Rivero-Melian, Rosario, & Grant, 1992;Tong et al, 1999) or into the L5 DRG (Robertson & Grant, 1985). We have seen, however, only little CTB labeling in the superfi- consideration is an immunohistochemical artifact as discussed in a previous study (Rivero-Melian et al, 1992) showing that the intensity of CTB detection varied with different combinations of primary and secondary antibodies.…”

Section: Central Projection Patterns Of a And C Fibers From Dcnsmentioning

confidence: 99%

Peripheral and central anatomical organization of cutaneous afferent subtypes in a rat nociceptive intersegmental spinal reflex

Lee

White

Chung

et al. 2017

J of Comparative Neurology

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Stimulation of rat segmental dorsal cutaneous nerves (DCNs) evokes the nociceptive intersegmental cutaneus trunci muscle (CTM) reflex. The reflex consists of early and late responses, mediated by Aδ and C fibers, respectively, based on required stimulation strengths, and shows segmental differences in terms of amplitude and duration. We have now investigated whether the peripheral or central anatomy of nociceptive afferent subtypes in different DCNs also vary in a segmental manner. The numbers of different axon subtypes, determined by axon diameter, were analyzed across peripheral DCNs from T6 to L1. The central projections of T7 and T13 DCN afferents were traced using DCN injections of cholera toxin subunit B (CTB) for myelinated A fibers and isolectin B4 (IB4) for unmyelinated C fibers and both labels were quantified in the dorsal horns. Peripheral axon subtype numbers did not differ significantly across DCNs. Centrally, IB4 , but not CTB , projection areas were different between T7 and T13, consistent with different segmental CTM neurogram responses. At both levels, A fibers projected to deeper layers of the dorsal horn than did C fibers. These termination sites are consistent with both mono- and polysynaptic connections between these afferents and the ascending propriospinal interneurons of the reflex. Also analyzed were the spatial distribution, the synaptic termination, and the glutamatergic transporter profiles of DCN A and C fibers and their relationship to calcitonin gene-related peptide (CGRP) staining in the dorsal horn.

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Selective innervation of NK1 receptor–lacking lamina I spinoparabrachial neurons by presumed nonpeptidergic Aδ nociceptors in the rat

Abstract: SummaryThis study provides evidence that nonpeptidergic Aδ nociceptive primary afferents selectively innervate lamina I spinoparabrachial projection neurons that lack the neurokinin 1 receptor.

Cited by 9 publications

References 71 publications

Nerve injury induced activation of fast-conducting high threshold mechanoreceptors predicts non-reflexive pain related behavior

Nerve injury induced activation of fast-conducting high threshold mechanoreceptors predicts non-reflexive pain related behavior

Combined 3DISCO clearing method, retrograde tracer and ultramicroscopy to map corneal neurons in a whole adult mouse trigeminal ganglion

Peripheral and central anatomical organization of cutaneous afferent subtypes in a rat nociceptive intersegmental spinal reflex

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