Transplants of Adrenal Medullary Chromaffin Cells Reduce Forelimb and Hindlimb Allodynia in a Rodent Model of Chronic Central Pain after Spinal Cord Hemisection Injury

Hains, Bryan C.; Chastain, Kathy M.; Everhart, Alex W.; McAdoo, David J.; Hulsebosch, Claire E.

doi:10.1006/exnr.2000.7439

Cited by 62 publications

(31 citation statements)

References 88 publications

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“…For example, Christensen and colleagues reported that unilateral hemisection at T13 produced mechanical and thermal allodynia and hyperalgesia in both the ipsilateral and contralateral forelimbs and hindlimbs (Christensen et al, 1996). Since that study, there have been several reports of hyperresponsiveness of the forelimbs following SCI (Hulsebosch et al, 1998;Bennett et al, 2000a,b;Hains et al, 2000Hains et al, , 2001. Therefore, it is possible that our animals may also experience a hyperresponsiveness to stimulation of the face and whisker barrels.…”

Section: Discussionmentioning

confidence: 87%

Differences in forebrain activation in two strains of rat at rest and after spinal cord injury

Paulson

Gorman²,

Yezierski

et al. 2005

Experimental Neurology

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Forebrain activation patterns in normal and spinal-injured Sprague-Dawley (SD) rats were determined by measuring regional cerebral blood flow as an indicator of neuronal activity. Data are compared to our previously published findings from normal and spinal-injured Long-Evans (LE) rats and reveal a striking degree of overlap, as well as differences, between strains in the basal (unstimulated) forebrain activation in normal animals. Specifically, 81% of the structures sampled showed similar activation in both strains, suggesting a consistent and identifiable pattern of basal cerebral activation in the rat. LE controls showed significantly greater basal activation in the remaining structures compared to SD control group, including the anterior dorsal thalamus, basolateral amygdala, SII cortex, and the hypothalamic paraventricular nucleus. In contrast, spinal cord injury (SCI) resulted in strain-specific changes in forebrain activation categorized by structures that showed significant increases in: (1) only LE SCI rats (posterior, ventrolateral, and ventroposterolateral thalamic nuclei); (2) only SD SCI rats (anterior-dorsal and medial thalamus, basolateral amygdala, cingulate and retrosplenial cortex, habenula, interpeduncular nucleus, hypothalamic paraventricular nucleus, periaqueductal gray); or (3) both strains (arcuate nucleus, ventroposteromedial thalamus, SI and SII somatosensory cortex). These results provide information related to the remote, i.e. supraspinal, effects of spinal cord injury and suggest that genetic differences play an important part in the forebrain response to such injury. Brain activation studies therefore provide a useful tool in understanding the full extent of secondary consequences following spinal injury and for identifying potential central mechanism responsible for the development of pain.

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Section: Discussionmentioning

confidence: 87%

Differences in forebrain activation in two strains of rat at rest and after spinal cord injury

Paulson

Gorman²,

Yezierski

et al. 2005

Experimental Neurology

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“…Using less intense stimuli, we showed that both groups of operated rats demonstrated the reduced latency that has been shown in other studies of SCI. (Hains et al, 2000(Hains et al, , 2002a(Hains et al, ,b, 2003bLindsey et al, 2000;Coumans et al, 2001;Shumsky et al, 2003;Gwak et al, 2004). NRP/GRP rats, however, recovered near normal latencies, consistent with a decrease in lesion-related hypersensitivity or pain.…”

Section: Recovery Of Sensorimotor Functionmentioning

confidence: 88%

“…The last four trials were averaged to provide the mean latency of withdrawal. This test has been shown to reveal a reduced latency to foot or tail withdrawal to thermal stimuli in rats with midthoracic hemisections (Hains et al, 2000;Coumans et al, 2001;Hains et al, 2002aHains et al, ,b, 2003bGwak et al, 2004) and cervical partial hemisections (Shumsky et al, 2003) and has been used as a model for neuropathic pain.…”

Section: Immunosuppression With Cyclosporine Amentioning

confidence: 99%

“…Withdrawal of limb or tail during noxious stimulation is an animal model for neuropathic pain (Hains et al, 2000;Lindsey et al, 2000;Coumans et al, 2001;Hains et al, 2002aHains et al, ,b, 2003bShumsky et al, 2003;Gwak et al, 2004), although it is recognized that hyperreflexia is difficult to differentiate from perception of pain in animals. When intense noxious stimulation is used in animals with incomplete lesions, vocalization is often evoked that provides behavioral support for the validity of this model.…”

Section: Recovery Of Sensorimotor Functionmentioning

confidence: 99%

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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

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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.

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“…Thermal Sensitivity-Because contusion and hemisection 34,[49][50][51] injuries have induced hypersensitivity to thermal stimuli applied to the hindlimb, we tested whether the more restricted lesion that we used would also increase sensitivity. We found increased sensitivity compared to baseline only in the op-control group and only at 2 weeks.…”

Section: Recovery Of Functionmentioning

confidence: 99%

Nogo-66 Receptor Antagonist Peptide (NEP1-40) Administration Promotes Functional Recovery and Axonal Growth After Lateral Funiculus Injury in the Adult Rat

Cao

Shumsky

Sabol

et al. 2008

Neurorehabil Neural Repair

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Objective-The myelin protein Nogo inhibits axon regeneration by binding to its receptor (NgR) on axons. Intrathecal delivery of an NgR antagonist (NEP1-40) promotes growth of injured corticospinal axons and recovery of motor function following a dorsal hemisection. The authors used a similar design to examine recovery and repair after a lesion that interrupts the rubrospinal tract (RST).Methods-Rats received a lateral funiculotomy at C4 and NEP1-40 or vehicle was delivered to the cervical spinal cord for 4 weeks. Outcome measures included motor and sensory tests and immunohistochemistry.Results-Gait analysis showed recovery in the NEP1-40-treated group compared to operated controls, and a test of forelimb usage also showed a beneficial effect. The density of labeled RST axons increased ipsilaterally in the NEP1-40 group in the lateral funiculus rostral to the lesion and contralaterally in both gray and white matter. Thus, rubrospinal axons exhibited diminished dieback and/or growth up to the lesion site. This was accompanied by greater density of 5 HT and calcitonin gene-related peptide axons adjacent to and into the lesion/matrix site in the NEP1-40 group.Conclusions-NgR blockade after RST injury is associated with axonal growth and/or diminished dieback of severed RST axons up to but not into or beyond the lesion/matrix site, and growth of serotonergic and dorsal root axons adjacent to and into the lesion/matrix site. NgR blockade also supported partial recovery of function. The authors' results indicate that severed rubrospinal axons respond to NEP1-40 treatment but less robustly than corticospinal, raphe-spinal, or dorsal root axons. Keywords Spinal cord injury; Rubrospinal tract; NEP1-40Adult mammalian central nervous system (CNS) neurons do not spontaneously regenerate their axons. Contributors to this failure include the local environment of both the normal and injured adult CNS, which contains inhibitors that constitute a biochemical and physical barrier to regeneration. 1 Three molecules associated with myelin have been identified: NogoA, [2][3][4][5] Address correspondence to Yang Cao, Dept of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129. yc94@drexel.edu. NIH Public Access Author ManuscriptNeurorehabil Neural Repair. Author manuscript; available in PMC 2010 April 12. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript myelin-associated glycoprotein (MAG), 6,7 and oligodendrocyte-myelin glycoprotein (OMgp). 8,9 Nogo has 3 variants: NogoA, NogoB, and NogoC. NogoA is mainly expressed in the CNS, whereas the other 2 are more widely expressed outside the CNS. NogoA possesses a transmembrane loop region, Nogo66, which inhibits neurite outgrowth. 10,11 The Nogo-66 receptor, NgR1, 12 is a glycosylphosphatidylinositol-linked cell surface receptor that contains a leucine-rich repeat motif that also interacts with MAG [13][14][15] and OMgp. 15,16 All 3 myelin molecules bind to NgR1 in a complex with p75 neurotrophin receptor and a leucine-...

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Transplants of Adrenal Medullary Chromaffin Cells Reduce Forelimb and Hindlimb Allodynia in a Rodent Model of Chronic Central Pain after Spinal Cord Hemisection Injury

Cited by 62 publications

References 88 publications

Differences in forebrain activation in two strains of rat at rest and after spinal cord injury

Differences in forebrain activation in two strains of rat at rest and after spinal cord injury

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

Nogo-66 Receptor Antagonist Peptide (NEP1-40) Administration Promotes Functional Recovery and Axonal Growth After Lateral Funiculus Injury in the Adult Rat

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