Noradrenergic projections to the spinal cord of the rat

Westlund, Karin N.; Bowker, Robert M.; Ziegler, Michael G.; Coulter, J.D.

doi:10.1016/0006-8993(83)91196-4

Cited by 468 publications

(165 citation statements)

References 56 publications

Supporting

Mentioning

146

Contrasting

Unclassified

Order By: Relevance

“…The noradrenergic descending inhibitory pathway is known to play an important role in endogenous analgesic systems, which project from A5 and A7 cell groups of the pons to the spinal dorsal horn (24). Therefore, we examined the involvement of the descending noradrenergic system in the regulation of chronic arthritic pain and analgesic effect of Neurotropin.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of Analgesic Action of Neurotropin on Chronic Pain in Adjuvant-Induced Arthritic Rat: Roles of Descending Noradrenergic and Serotonergic Systems

et al. 2005

View full text Add to dashboard Cite

Abstract. Neurotropin ® , a non-protein extract from the inflamed skin of rabbits inoculated with vaccinia virus, has been clinically used as an analgesic drug for treatment of chronic pain. In this study, we investigated the analgesic mechanisms of Neurotropin in the adjuvant-induced arthritic rat, a chronic pain model with inflammation. Neurotropin caused dose-dependent inhibition of hyperalgesia in the adjuvant-induced arthritic rat after single intravenous (10 -100 NU / kg) and oral (30 -200 NU / kg) administration. The analgesic effect of Neurotropin (intravenous 100 NU / kg and oral 200 NU/ kg) was significantly inhibited by intrathecal injections of the a 2 -adrenoceptor antagonist yohimbine (30 nmol / animal) and the selective 5-HT 3 serotonin receptor antagonist MDL72222 (30 nmol / animal), and slightly inhibited by the non-selective serotonin receptor antagonist methysergide (100 nmol / animal). The results suggest that the analgesic action of Neurotropin is at least in part due to the enhancement of noradrenergic and serotonergic descending pain inhibitory pathways. Neurotropin may be useful for the clinical management of chronic pain diseases such as a rheumatoid arthritis and osteoarthritis.

show abstract

Section: Discussionmentioning

confidence: 99%

Mechanisms of Analgesic Action of Neurotropin on Chronic Pain in Adjuvant-Induced Arthritic Rat: Roles of Descending Noradrenergic and Serotonergic Systems

et al. 2005

View full text Add to dashboard Cite

show abstract

“…Noradrenergic axons from the brainstem project to the lumbosacral spinal cord innervating the lower urinary tract (Westlund et al, 1983;Vizzard et al, 1995;Marson, 1997), including the SPN. These inputs, particularly from the locus ceruleus, have been implicated in the supraspinal control of micturition.…”

Section: Descending Modulatory Pathwaysmentioning

confidence: 99%

Transplantation of Neuronal and Glial Restricted Precursors into Contused Spinal Cord Improves Bladder and Motor Functions, Decreases Thermal Hypersensitivity, and Modifies Intraspinal Circuitry

Mitsui¹,

Shumsky²,

Lepore³

et al. 2005

J. Neurosci.

170

187

View full text Add to dashboard Cite

Transplanting neuronal and glial restricted precursors (NRP/GRP) into a midthoracic injury 9 d after contusion improved bladder and motor function, diminished thermal hypersensitivity, and modified lumbosacral circuitry compared with operated controls (OPcontrols). Histological analysis showed that NRP/GRP survived, filled the lesion site, differentiated into neurons and glia, and migrated selectively. Volume of spinal cord spared was increased in NRP/GRP recipients, suggesting local protection. Bladder areflexia developed in both operated groups, but NRP/GRP recipients exhibited an accelerated recovery, with decreased micturition pressure and fewer episodes of detrusor hyperreflexia. Because noradrenergic receptors proliferate after spinal injury and descending noradrenergic pathways contribute to regulation of bladder control, we examined the effects of administering an ␣-1A-adrenergic antagonist, Tamsulosin, on urodynamics. This improved all cystometric parameters in both operated groups, and micturition pressure in NRP/GRP rats recovered to normal levels. Both operated groups initially showed increased sensitivity to a thermal stimulus applied to the tail; the NRP/GRP rats showed significant improvement over time. NRP/GRP grafts also produced greater recovery of hindlimb function in several tests, although both groups showed persistent and similar deficits in locomotion on a grid.Because bladder, hindlimb, and tail sensory and motor functions are organized through lumbosacral cord, we examined descending and primary afferent projections at L6 -S1. The density of serotonergic, noradrenergic, and corticotrophin releasing factor-positive fibers increased in the NRP/GRP group compared with OP-controls, suggesting some sparing and/or sprouting of these modulatory pathways. Immunocytochemical staining density of dorsal root axons in the dorsal horn increased in the OP-controls but appeared normal in the NRP/GRP group. Synaptophysin immunoreactivity in the lumbosacral dorsal horn was similar among groups, consistent with restoration of synaptic density in both groups of operated animals but by different pathways. We suggest that local protection provided by NRP/GRP resulted in increased sparing/sprouting of descending pathways, which prevented sprouting by dorsal root axons, and that this modification in lumbosacral circuitry contributes to the recovery of function.

show abstract

“…5,6 Brainstem-spinal noradrenergic axons project to the lumbosacral spinal cord including the sacral parasympathetic nucleus (SPN) whose axons innervate the LUT. 5,7 In SCI, disruption of these modulatory descending pathways induces sprouting of the small-diameter dorsal root afferents, for example, calcitonin gene-related peptide (CGRP)-positive fibers 3 in the DH. If the descending fibers are partially preserved even in a clinically compete injury of the spinal cord, they could offer targets for LUT treatment even after severe SCI.…”

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Lower urinary tract function in spinal cord-injured rats: midthoracic contusion versus transection

2014

View full text Add to dashboard Cite

Objectives: To compare changes in lower urinary tract (LUT) function with modifications in pathways that regulate LUT function using two different animal models (incomplete and complete) of spinal cord injury (SCI). Methods: Female Sprague-Dawley rats were used. SCI was made at Th8/9 by a contusion injury (contusion, n ¼ 9) or a complete transection (transection, n ¼ 9). Unoperated rats were used as normal controls (normal, n ¼ 6). LUT function was evaluated by micturition behavior in metabolic cages for 24 h and cystometry in awake animals. Immunocytochemical staining at the L6 spinal cord, spinal areas associated with LUT, was performed to identify descending modulatory fibers and dorsal root afferents that project to the L6 spinal cord. Results: Volume/micturition in metabolic cages gradually increased in both contusion and transection groups compared with normals, and operated groups did not differ from each other. Urodynamic parameters from cystometry were significantly different in contusion and transection groups compared with normals, but again there was no significant difference between contusion and transection groups. Immunocytochemical analyses at the L6 spinal cord showed no serotonergic or noradrenergic fibers in transection group, but some descending fibers remained in contusion group, indicating sparing. Small dorsal root afferents were denser in both contusion and transection groups than in normals, indicating sprouting. Conclusions: Although differences were not found in LUT function in operated animals, supraspinal and dorsal root projections to the L6 spinal cord responded differently to contusion and transection. This suggests that the benefits of pharmacologic treatments may be different in two lesion models. Spinal Cord (2014) 52, 658-661; doi:10.1038/sc.2014.114; published online 15 July 2014 INTRODUCTION Spinal cord injury (SCI) is classified clinically into complete injuries,where function below the level of a injury is lost, and incomplete injuries where some sensory and/or motor function is retained. Nevertheless, it is known that some descending pathways are spared in many cases of clinically complete injuries. 1 Lower urinary tract (LUT) dysfunction in SCI results from damage to descending modulatory pathways and increased sensory input through sprouting of primary afferent pathways. A contusion injury that we use destroys the dorsal spinal cord in the thoracic region, including the dorsal columns, the corticospinal tract and the dorsolateral (DL) funiculus, damages the dorsal horn (DH) and impinges on the intermediolateral column. 2-4 Thus, the ventral funiculi and the ventral portions of the lateral funiculi, which contain descending modulatory pathways, were partially spared in contusion injuries, but not in transection injuries.Serotonergic axons project to the DL nucleus in the spinal cord, which has been implicated in the central control of the bladder and the urethra and recovery of bladder-external urethral sphincter coordination in SCI rats. 5,6 Brainstem-spinal noradrenerg...

show abstract

Noradrenergic projections to the spinal cord of the rat

Cited by 468 publications

References 56 publications

Mechanisms of Analgesic Action of Neurotropin on Chronic Pain in Adjuvant-Induced Arthritic Rat: Roles of Descending Noradrenergic and Serotonergic Systems

Mechanisms of Analgesic Action of Neurotropin on Chronic Pain in Adjuvant-Induced Arthritic Rat: Roles of Descending Noradrenergic and Serotonergic Systems

Transplantation of Neuronal and Glial Restricted Precursors into Contused Spinal Cord Improves Bladder and Motor Functions, Decreases Thermal Hypersensitivity, and Modifies Intraspinal Circuitry

Lower urinary tract function in spinal cord-injured rats: midthoracic contusion versus transection

Contact Info

Product

Resources

About