Effects of spinal nerve ligation on immunohistochemically identified neurons in the L4 and L5 dorsal root ganglia of the rat

Hammond, Donna L.; Ackerman, Laurie L.; Holdsworth, Ryan; Elzey, Brian

doi:10.1002/cne.20209

Cited by 82 publications

(110 citation statements)

References 76 publications

(105 reference statements)

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“…In agreement with our findings, TRPV1 transcripts and protein are selectively increased in uninjured ipsilateral L4 DRG neurons after SNL (Hudson et al, 2001;Fukuoka et al, 2002). In the injured ipsilateral L5 DRG we find significantly decreased IB4 and CGRP labeling and a trend to decreased TRPV1 and NR2C/ D. Similar decreases in IB4 and CGRP but not N52 labeling were demonstrated after SNL (Hammond et al, 2004). Profoundly altered gene expression of various receptors, neuropeptides and ion channels occurs in both injured L5 and uninjured L4 DRG .…”

Section: Increased Cb 1 R Transcripts and Protein In Uninjured L4 Drgsupporting

confidence: 91%

Site-specific increases in peripheral cannabinoid receptors and their endogenous ligands in a model of neuropathic pain

Mitrirattanakul

Ramakul

Guerrero

et al. 2006

Pain

185

143

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Selective activation of the peripheral cannabinoid receptor 1 (CB 1 R) has been shown to suppress neuropathic pain symptoms in rodents. However, relatively little is known about changes in CB 1 R and its endogenous ligands during development or maintenance of neuropathic pain. Using immunohistochemistry, Western blot, real-time reverse transcription polymerase chain reaction, as well as liquid chromatography/mass spectrometry, we studied the changes in CB 1 Rs and endocannabinoids N-arachidonoylethanolamine/anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in rat lumbar (L4 and L5) dorsal root ganglia (DRG) after neuropathic pain induction (L5 spinal nerve ligation: SNL). Immunohistochemistry revealed that in control rats, CB 1 R is expressed in the majority (76-83%) of nociceptive neurons as indicated by co-labeling with isolectin B4 (IB4) or antibodies recognizing transient receptor potential vanilloid (TRPV1), calcitonin gene related peptide (CGRP), and the NR2C/2D subunits of the N-methyl-D-aspartate receptor. After L5 SNL, CB 1 R mRNA and protein increases in the ipsilateral uninjured L4 DRG whereas the percentages of CB 1 R immunoreactive (CB 1 R-ir) neurons remain unchanged in L4 and L5 DRG. However, for these CB 1 R-ir neurons, we observe significant increases in percentage of TRPV1-ir cells in ipsilateral L4 DRG, and decreases in percentage of IB4-and CGRP-co-labeled cells in ipsilateral L5 DRG. Levels of both AEA and 2-AG increase significantly only in the ipsilateral L5 DRG. These results are consistent with the preserved analgesic effects of cannabinoids in neuropathic pain and provide a rational framework for the development of peripherally acting endocannabinoid-based therapeutic interventions for neuropathic pain.

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Section: Increased Cb 1 R Transcripts and Protein In Uninjured L4 Drgsupporting

confidence: 91%

Site-specific increases in peripheral cannabinoid receptors and their endogenous ligands in a model of neuropathic pain

Mitrirattanakul

Ramakul

Guerrero

et al. 2006

Pain

185

143

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“…Anti-NF200 specifically recognizes the neurofilaments with a molecular weight of 200 kDa on immunoblots from rat spinal cord and does not crossreact with other intermediate filament proteins (manufacturer's technical information). Anti-NF200 has been established as a marker of DRG neurons having (Hammond et al, 2004;Lawson and Waddell, 1991;Ruscheweyh et al, 2007). The pattern of staining obtained in our experiments with this antibody was similar to that previously reported for DRG from other studies (Chao et al, 2008;Keast et al, 2010;Ruscheweyh et al, 2007;Schumacher et al, 1999).…”

Section: Primary Antibody Characterizationsupporting

confidence: 77%

Morphological and functional characterization of cholinergic interneurons in the dorsal horn of the mouse spinal cord

Mesnage

Gaillard

Godin

et al. 2011

J of Comparative Neurology

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Endogenous acetylcholine is an important modulator of sensory processing, especially at the spinal level, where nociceptive (pain-related) stimuli enter the central nervous system and are integrated before being relayed to the brain. To decipher the organization of the local cholinergic circuitry in the spinal dorsal horn, we used transgenic mice expressing enchanced green fluorescent protein specifically in cholinergic neurons (ChAT::EGFP) and characterized the morphology, neurochemistry, and firing properties of the sparse population of cholinergic interneurons in this area. Three-dimensional reconstruction of lamina III ChAT::EGFP neurons based either on their intrinsic fluorescence or on intracellular labeling in live tissue demonstrated that these neurons have long and thin processes that grow preferentially in the dorsal direction. Their dendrites and axon are highly elongated in the rostrocaudal direction, beyond the limits of a single spinal segment. These unique morphological features suggest that dorsal horn cholinergic interneurons are the main contributors to the plexus of cholinergic processes located in lamina IIi, just dorsal to their cell bodies. In addition, immunostainings demonstrated that dorsal horn cholinergic interneurons in the mouse are γ-aminobutyric acidergic and express nitric oxide synthase, as in rats. Finally, electrophysiological recordings from these neurons in spinal cord slices demonstrate that two-thirds of them have a repetitive spiking pattern with frequent rebound spikes following hyperpolarization. Altogether our results indicate that, although they are rare, the morphological and functional features of cholinergic neurons enable them to collect segmental information in superficial layers of the dorsal horn and to modulate it over several segments.

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“…The presence of tetramethylrhodamine dextran in large diameter DRG neurons is consistent with direct projections of Aβ fibers to the n. gracilis. These cell bodies do not express substance P or CGRP in either the basal or injured state (Ma and Bisby, 1998;Macdonald et al 2001;Hammond et al 2004). …”

Section: Discussionmentioning

confidence: 99%

Nerve injury-induced tactile allodynia is present in the absence of FOS labeling in retrogradely labeled post-synaptic dorsal column neurons

Zhang

Ossipov

Zhang

et al. 2007

Pain

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The dorsal column pathway consists of direct projections from primary afferents and of ascending fibers of the post-synaptic dorsal column (PSDC) cells. This pathway mediates touch but may also mediate allodynia after nerve injury. The role of PSDC neurons in nerve injury-induced mechanical allodynia is unknown. Repetitive gentle, tactile stimulus or noxious pinch was applied to the ipsilateral hindpaw of rats with spinal nerve ligation (SNL) or sham surgery that had previously received tetramethylrhodamine dextran in the ipsilateral n. gracilis. Both touch and noxious stimuli produced marked increases in FOS expression in other cells throughout all laminae of the ipsilateral dorsal horn after nerve injury. However, virtually none of the identified PSDC cells expressed FOS immunofluorescence in response to repetitive touch or pinch in either the nerve-injured or sham groups. In contrast, labeled PSDC cells expressed FOS in response to ureter ligation and labeled spinothalamic tract (STT) cells expressed FOS in response to noxious pinch. Identified PSDC neurons from either sham-operated or SNL rats did not express immunoreactivity to substance P, CGRP, NPY, PKCg, MOR, the NK1 and the NPY-Y1 receptor. Retrogradely labeled DRG cells of nerve injured rats were large diameter neurons, which expressed NPY, but no detectable CGRP or substance P. Spinal nerve injury sensitizes neurons in the spinal dorsal horn to repetitive light touch but PSDC neurons apparently do not participate in touch-evoked allodynia. Sensitization of these non-PSDC neurons may result in activation of projections integral to the spinal/supraspinal processing of enhanced pain states and of descending facilitation, thus priming the central nervous system to interpret tactile stimuli as being aversive.

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Effects of spinal nerve ligation on immunohistochemically identified neurons in the L4 and L5 dorsal root ganglia of the rat

Cited by 82 publications

References 76 publications

Site-specific increases in peripheral cannabinoid receptors and their endogenous ligands in a model of neuropathic pain

Site-specific increases in peripheral cannabinoid receptors and their endogenous ligands in a model of neuropathic pain

Morphological and functional characterization of cholinergic interneurons in the dorsal horn of the mouse spinal cord

Nerve injury-induced tactile allodynia is present in the absence of FOS labeling in retrogradely labeled post-synaptic dorsal column neurons

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