Morphological identification of thoracolumbar spinal afferent nerve endings in mouse uterus

Dodds, Kelsi N.; Kyloh, Melinda; Travis, Lee Edward; Beckett, Elizabeth; Spencer, Nick J.

doi:10.1002/cne.25070

Cited by 6 publications

(10 citation statements)

References 32 publications

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“…In any case, the present study replicated a separate finding from the rat, in that CGRPexpressing nerve fibers were intrinsically more concentrated within the cranial region of the uterine horn, compared to the middle and caudal portions (Zoubina et al, 1998). Use of CGRP as a sensory marker is in line with our recent study that identified spinal afferent nerve endings in the mouse uterus for the first time (Dodds et al, 2021). Other neurochemical markers that label sensory neurons (such as substance P) may reveal a different pattern innervation to the mouse uterine horn following DRG removal.…”

Section: Discussionsupporting

confidence: 91%

“…Here, we demonstrate that CGRP-expressing lumbosacral spinal afferent neurons supply relatively minor innervation across the mouse uterine horn. Subsequent retrograde neuronal tracing confirmed that few lumbosacral spinal afferent neurons innervate the caudal uterine horn, with a greater proportion arising from thoracolumbar DRG; consistent with tracing from the mid and whole uterus (Herweijer et al, 2014;Dodds et al, 2021). Collectively, these findings suggest that sensory information between the mouse uterine horn and central nervous system is primarily relayed via thoracolumbar spinal afferent neurons.…”

Section: Discussionsupporting

confidence: 60%

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Anatomical distribution of CGRP-containing lumbosacral spinal afferent neurons in the mouse uterine horn

Dodds

Kyloh²,

Travis³

et al. 2022

Front. Neurosci.

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Sensory stimuli from the uterus are detected by spinal afferent neurons whose cell bodies arise from thoracolumbar and lumbosacral dorsal root ganglia (DRG). Using an in vivo survival surgical technique developed in our laboratory to remove select DRG from live mice, we recently quantified the topographical distribution of thoracolumbar spinal afferents innervating the mouse uterine horn, revealed by loss of immunoreactivity to calcitonin gene-related peptide (CGRP). Here, we used the same technique to investigate the distribution of lumbosacral uterine spinal afferents, in which L5-S1 DRG were unilaterally removed from adult female C57BL/6J mice (N = 6). Following 10–12 days recovery, CGRP immunoreactivity was quantified along the length of uterine horns using fluorescence immunohistochemistry. Relative to myometrial thickness, overall CGRP density in uterine tissues ipsilateral to L5-S1 DRG removal was reduced compared to the DRG-intact, contralateral side (P = 0.0265). Regionally, however, myometrial CGRP density was unchanged in the cranial, mid, and caudal portions. Similarly, CGRP-expressing nerve fiber counts, network lengths, junctions, and the proportion of area occupied by CGRP immunoreactivity were unaffected by DRG removal (P ≥ 0.2438). Retrograde neuronal tracing from the caudal uterine horn revealed fewer spinal afferents here arise from lumbosacral than thoracolumbar DRG (P = 0.0442) (N = 4). These data indicate that, unlike thoracolumbar DRG, lumbosacral spinal afferent nerves supply relatively modest sensory innervation across the mouse uterine horn, with no regional specificity. We conclude most sensory information between the mouse uterine horn and central nervous system is likely relayed via thoracolumbar spinal afferents.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 60%

Anatomical distribution of CGRP-containing lumbosacral spinal afferent neurons in the mouse uterine horn

Dodds

Kyloh²,

Travis³

et al. 2022

Front. Neurosci.

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“…Sensory innervation to the mouse uterus is predominantly supplied by spinal afferents arising from T13-L2 DRG, with a minority arising from L6-S1 21 , 22 . The lateralisation of this organ affords the opportunity for internal controls with unilateral DRG lesions.…”

Section: Resultsmentioning

confidence: 99%

“…Obviously, the difference between the two techniques is we do not remove the DRG, once we have injected DRGs with tracers. By injecting minute quantities of neuronal tracer into single DRG, it has been demonstrated we can readily identify the nerve endings that arise from a single DRG neuron 22 , 27 , 28 . This cannot be achieved using transgenic reporter or cre-induced expression of fluorescent reporters, which label large populations of axons whose spatial fields overlap extensively; see ref.…”

Section: Discussionmentioning

confidence: 99%

Disengaging spinal afferent nerve communication with the brain in live mice

et al. 2022

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Our understanding of how abdominal organs (like the gut) communicate with the brain, via sensory nerves, has been limited by a lack of techniques to selectively activate or inhibit populations of spinal primary afferent neurons within dorsal root ganglia (DRG), of live animals. We report a survival surgery technique in mice, where select DRG are surgically removed (unilaterally or bilaterally), without interfering with other sensory or motor nerves. Using this approach, pain responses evoked by rectal distension were abolished by bilateral lumbosacral L5-S1 DRG removal, but not thoracolumbar T13-L1 DRG removal. However, animals lacking T13-L1 or L5-S1 DRG both showed reduced pain sensitivity to distal colonic distension. Removal of DRG led to selective loss of peripheral CGRP-expressing spinal afferent axons innervating visceral organs, arising from discrete spinal segments. This method thus allows spinal segment-specific determination of sensory pathway functions in conscious, free-to-move animals, without genetic modification.

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“…Neuroanatomical studies performed in rodents show sensory afferents innervating the urogenital organs and colon are predominantly peptidergic (containing substance P, calcitonin gene-related peptide) [56][57][58]. There is also strong evidence for convergence of bladder and colon sensory innervation at the level of primary afferents, and peripheral sensitization of urinary bladder and pelvic nerve afferents in the setting of colonic irritation, which potentially contribute to disorders characterized by chronic pelvic pain [57,59].…”

Section: Antinociceptive Effects In Animal Models Of Bladder Pain Syndrome and Endometriosismentioning

confidence: 99%

Guanylate cyclase-C agonists as peripherally acting treatments of chronic visceral pain

Brierley

Grundy

Castro

et al. 2022

Trends in Pharmacological Sciences

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Morphological identification of thoracolumbar spinal afferent nerve endings in mouse uterus

Cited by 6 publications

References 32 publications

Anatomical distribution of CGRP-containing lumbosacral spinal afferent neurons in the mouse uterine horn

Anatomical distribution of CGRP-containing lumbosacral spinal afferent neurons in the mouse uterine horn

Disengaging spinal afferent nerve communication with the brain in live mice

Guanylate cyclase-C agonists as peripherally acting treatments of chronic visceral pain

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