scholarly journals Contralateral Metabolic Activation Related to Plastic Changes in the Spinal Cord after Peripheral Nerve Injury in Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Ran Won ◽  
Bae Hwan Lee
Keyword(s):  
Spinal Cord ◽  
Nerve Injury ◽  
Mechanical Allodynia ◽  
Metabolic Activation ◽  
Ventral Horn ◽  
Withdrawal Reflex ◽  
Plastic Changes ◽  
Metabolic Activities ◽  
Unilateral Nerve Injury ◽  
Stimulation Of

We have previously reported the crossed-withdrawal reflex in which the rats with nerve injury developed behavioral pain responses of the injured paw to stimuli applied to the contralateral uninjured paw. This reflex indicates that contralateral plastic changes may occur in the spinal cord after unilateral nerve injury. The present study was performed to elucidate the mechanisms and morphological correlates underlying the crossed-withdrawal reflex by using quantitative14C-2-deoxyglucose (2-DG) autoradiography which can examine metabolic activities and spatial patterns simultaneously. Under pentobarbital anesthesia, rats were subjected to unilateral nerve injury. Mechanical allodynia was tested for two weeks after nerve injury. After nerve injury, neuropathic pain behaviors developed progressively. The crossed-withdrawal reflex was observed at two weeks postoperatively. Contralateral enhancement of 2-DG uptake in the ventral horn of the spinal cord to electrical stimulation of the uninjured paw was observed. These results suggest that the facilitation of information processing from the uninjured side to the injured side may contribute to the crossed-withdrawal reflex by plastic changes in the spinal cord of nerve-injured rats.

Sortilins in neuropathic pain

2012 ◽  
Vol 3 (3) ◽  
pp. 183-184
Author(s):  
M. Richner ◽  
O.J. Bjerrum ◽  
Y. De Koninck ◽  
A. Nykjaer ◽  
C.B. Vaegter
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Mechanical Allodynia ◽  
Molecular Mechanisms ◽  
Intrathecal Injection ◽  
Ion Concentration ◽  
Down Regulation

AbstractBackground/aimsThe molecular mechanisms underlying neuropathic pain are incompletely understood, but recent data suggest that down-regulation of the chloride extruding co-transporter KCC2 in spinal cord sensory neurons is critical: Following peripheral nerve injury, activated microglia in the spinal cord release BDNF, which stimulates neuronal TrkB receptors and ultimately results in the reduction of KCC2 levels. Consequently, neuronal intracellular chloride ion concentration increases, impairing GABAA-receptor mediated inhibition. We have previously described how the receptor sortilin modulates neurotrophin signaling by facilitating anterograde transport of Trk receptors. Unpublished data further link SorCS2, another member of the Sortilins family of sorting receptors (sortilin, SorLA and SorCS1–3) to BDNF signaling by regulating presynaptic TrkB trafficking. The purpose of this study is to explore the involvement of Sortilins in neuropathic pain.MethodsWe subjected wild-type (wt), sortilin knockout (Sort1-/-) and SorCS2 knockout (SorCS2-/-) mice to the Spared Nerve Injury (SNI) model of peripheral nerve injury. Mechanical allodynia was measured by von Frey filaments using the up-down-up method and a 3-out-of-5 thresshold.ResultsAs previously described by several groups, wt mice developed significant mechanical allodynia following SNI. Interestingly however, mice lacking sortilin or SorCS2 were fully protected from development of allodynia and did not display KCC2 down-regulation following injury. In addition, a single intrathecal injection of antibodies against sortilin or SorCS2 could delay or rescue mechanical allodynia in wt SNI mice for 2-3 days. Finally, neither sortilin nor SorCS2 deficient mice responded to intrathecal injection of BDNF, in contrast to wt mice which developed transient mechanical allodynia.ConclusionWe hypothesize that sortilin and SorCS2 are involved in neuropathic pain development by regulating TrkB signaling. Alternatively, Sortilins may directly influence the regulation of KCC2 membrane levels following injury. Both hypotheses are currently being investigated by our group.

scholarly journals Suppression of Superficial Microglial Activation by Spinal Cord Stimulation Attenuates Neuropathic Pain Following Sciatic Nerve Injury in Rats

2020 ◽  
Vol 21 (7) ◽  
pp. 2390
Author(s):  
Masamichi Shinoda ◽  
Satoshi Fujita ◽  
Shiori Sugawara ◽  
Sayaka Asano ◽  
Ryo Koyama ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Electrical Stimulation ◽  
Dorsal Horn ◽  
Nerve Injury ◽  
Spinal Cord Stimulation ◽  
Microglial Activation ◽  
In Vivo Optical Imaging ◽  
Stimulation Of

We evaluated the mechanisms underlying the spinal cord stimulation (SCS)-induced analgesic effect on neuropathic pain following spared nerve injury (SNI). On day 3 after SNI, SCS was performed for 6 h by using electrodes paraspinally placed on the L4-S1 spinal cord. The effects of SCS and intraperitoneal minocycline administration on plantar mechanical sensitivity, microglial activation, and neuronal excitability in the L4 dorsal horn were assessed on day 3 after SNI. The somatosensory cortical responses to electrical stimulation of the hind paw on day 3 following SNI were examined by using in vivo optical imaging with a voltage-sensitive dye. On day 3 after SNI, plantar mechanical hypersensitivity and enhanced microglial activation were suppressed by minocycline or SCS, and L4 dorsal horn nociceptive neuronal hyperexcitability was suppressed by SCS. In vivo optical imaging also revealed that electrical stimulation of the hind paw-activated areas in the somatosensory cortex was decreased by SCS. The present findings suggest that SCS could suppress plantar SNI-induced neuropathic pain via inhibition of microglial activation in the L4 dorsal horn, which is involved in spinal neuronal hyperexcitability. SCS is likely to be a potential alternative and complementary medicine therapy to alleviate neuropathic pain following nerve injury.

Comprehensive analysis of neurobehavior associated with histomorphological alterations in a chronic constrictive nerve injury model through use of the CatWalk XT system

2014 ◽  
Vol 120 (1) ◽  
pp. 250-262 ◽  
Author(s):  
Chien-Yi Chiang ◽  
Meei-Ling Sheu ◽  
Fu-Chou Cheng ◽  
Chun-Jung Chen ◽  
Hong-Lin Su ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Nerve Injury ◽  
Mechanical Allodynia ◽  
S100 Protein ◽  
Thermal Hyperalgesia ◽  
Nerve Damage ◽  
Dorsal Spinal Cord ◽  
Sensory Evoked ◽  
Dorsal Spinal

Object Neuropathic pain is debilitating, and when chronic, it significantly affects the patient physically, psychologically, and socially. The neurobehavior of animals used as a model for chronic constriction injury seems analogous to the neurobehavior of humans with neuropathic pain. However, no data depicting the severity of histomorphological alterations of the nervous system associated with graded changes in neurobehavior are available. To determine the severity of histomorphological alteration related to neurobehavior, the authors created a model of chronic constrictive injury of varying intensity in rats and used the CatWalk XT system to evaluate neurobehavior. Methods A total of 60 Sprague-Dawley rats, weighing 250–300 g each, were randomly assigned to 1 of 5 groups that would receive sham surgery or 1, 2, 3, or 4 ligatures of 3-0 chromic gut loosely ligated around the left sciatic nerve. Neurobehavior was assessed by CatWalk XT, thermal hyperalgesia, and mechanic allodynia before injury and periodically after injury. The nerve tissue from skin to dorsal spinal cord was obtained for histomorphological analysis 1 week after injury, and brain evoked potentials were analyzed 4 weeks after injury. Results. Significant differences in expression of nerve growth factor existed in skin, and the differences were associated with the intensity of nerve injury. After injury, expression of cluster of differentiation 68 and tumor necrosis factor–α was increased, and expression of S100 protein in the middle of the injured nerve was decreased. Increased expression of synaptophysin in the dorsal root ganglion and dorsal spinal cord correlated with the intensity of injury. The amplitude of sensory evoked potential increased with greater severity of nerve damage. Mechanical allodynia and thermal hyperalgesia did not differ significantly among treatment groups at various time points. CatWalk XT gait analysis indicated significant differences for print areas, maximum contact maximum intensity, stand phase, swing phase, single stance, and regular index, with sham and/or intragroup comparisons. Conclusions. Histomorphological and electrophysiological alterations were associated with severity of nerve damage. Subtle neurobehavioral differences were detected by the CatWalk XT system but not by mechanical allodynia or thermal hyperalgesia. Thus, the CatWalk XT system should be a useful tool for monitoring changes in neuropathic pain, especially subtle alterations.

scholarly journals Effects of antidromic stimulation of the ventral root on glucose utilization in the ventral horn of the spinal cord in the rat.

1987 ◽  
Vol 84 (15) ◽  
pp. 5492-5495 ◽  
Author(s):  
M. Kadekaro ◽  
W. H. Vance ◽  
M. L. Terrell ◽  
H. Gary ◽  
H. M. Eisenberg ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Glucose Utilization ◽  
Ventral Horn ◽  
Ventral Root ◽  
Antidromic Stimulation ◽  
Stimulation Of

scholarly journals Polyamidoamine dendrimer-conjugated triamcinolone acetonide attenuates nerve injury-induced spinal cord microglia activation and mechanical allodynia

2017 ◽  
Vol 13 ◽  
pp. 174480691769700 ◽  
Author(s):  
Hwisung Kim ◽  
Boomin Choi ◽  
Hyoungsub Lim ◽  
Hyunjung Min ◽  
Jae Hoon Oh ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Triamcinolone Acetonide ◽  
Nerve Injury ◽  
Mechanical Allodynia ◽  
Microglia Activation ◽  
Polyamidoamine Dendrimer

Effects of reversible spinalization on the visceral input to viscerosomatic neurons in the lower thoracic spinal cord of the cat

1986 ◽  
Vol 56 (3) ◽  
pp. 785-796 ◽  
Author(s):  
J. E. Tattersall ◽  
F. Cervero ◽  
B. M. Lumb
Keyword(s):  
Spinal Cord ◽  
Background Activity ◽  
Ventral Horn ◽  
Descending Inhibition ◽  
Thoracic Spinal Cord ◽  
Thoracic Spinal ◽  
Afferent Fibers ◽  
Biliary Pressure ◽  
Subcutaneous Tissues ◽  
Stimulation Of

Single-unit electrical activity has been recorded from 122 viscerosomatic neurons in the T9 and T11 segments of the cat's spinal cord. These neurons were excited by electrical and/or natural stimulation of visceral and somatic afferent fibers. The majority of viscerosomatic neurons (72%) received somatic nociceptive inputs, either exclusively or together with low-threshold somatic inputs. Many of these neurons were excited most strongly by intense mechanical stimulation of subcutaneous tissues, particularly by pinching or squeezing muscle. Twelve viscerosomatic neurons were excited by distensions of the biliary system at levels of biliary pressure greater than 25 mmHg. These intensities of biliary stimulation evoked transient increases in blood pressure, which suggest that the visceral stimuli were of nociceptive nature. The effects of reversible spinalization by cold block were tested on 98 viscerosomatic neurons. Three subgroups of viscerosomatic neurons were distinguished depending on whether their responses to visceral afferent stimulation were increased, decreased, or unchanged in the spinal state. Forty percent of all neurons tested increased the intensity of their responses to visceral stimulation in the spinal state. In addition, many of these neurons developed or increased their background activity and increased their somatic responses in the spinal state. It is concluded that these neurons were subjected to tonic descending inhibition of both somatic and visceral afferent inputs. More than 40% of the neurons in this group were located in or close to lamina V of the dorsal horn. In 44% of all neurons tested the response to visceral stimulation was reduced or abolished by spinalization. The background activity was not affected in the same manner and sometimes even increased during spinalization. The responses to somatic stimuli were fully tested in 11 neurons of this group and were found to be decreased, but not abolished, in nine neurons, unchanged in one cell, and increased in another one. Many of the neurons in this group were located in the ventral horn (laminae VII and VIII). Sixteen percent of all viscerosomatic neurons tested showed no change in their responses to visceral stimulation during spinalization. It is concluded that the visceral input to viscerosomatic neurons in the lower thoracic spinal cord is under considerable descending control, which includes excitation as well as tonic inhibition of visceral afferent information. This may represent part of the widespread effects of visceral nociceptive stimulation.

scholarly journals Downstream projection of Barrington's nucleus to the spinal cord in mice

2021 ◽  
Author(s):  
Masahiro Kawatani ◽  
William deGroat ◽  
Keiichi Itoi ◽  
Katsuya Uchida ◽  
Kenji Sakimura ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Ventral Horn ◽  
Projection Neurons ◽  
Patch Clamp Recording ◽  
Synaptic Currents ◽  
Lumbosacral Spinal Cord ◽  
Neuronal Populations ◽  
Adult Mice ◽  
Spinal Circuitry ◽  
Stimulation Of

Barrington's nucleus (Bar) which controls micturition behavior through downstream projections to the spinal cord contains two types of projection neurons BarCRH and BarESR1 that have different functions and target different spinal circuitry. Both types of neurons project to the L6-S1 spinal intermediolateral (IML) nucleus while BarESR1 neurons also project to the dorsal commissural nucleus (DCN). To obtain more information about the spinal circuits targeted by Bar, we used patch-clamp recording in spinal slices from adult mice in combination with optogenetic stimulation of Bar terminals. Recording of opto-evoked excitatory post synaptic currents (oEPSCs) in DiI-labeled lumbosacral preganglionic neurons (LS-PGN) revealed that both Bar neuronal populations make strong glutamatergic monosynaptic connections with LS-PGN, while BarESR1 neurons also elicited smaller amplitude glutamatergic polysynaptic oEPSCs or polysynaptic inhibitory post synaptic currents (oIPSCs) in some LS-PGN. Optical stimulation of BarCRH and BarESR1 terminals also elicited monosynaptic oEPSCs and polysynaptic oIPSCs in sacral DCN neurons, some of which must include interneurons projecting either to the IML or ventral horn. Application of capsaicin increased opto-evoked firing during repetitive stimulation of Bar terminals through the modulation of spontaneous post synaptic currents in LS-PGN. In conclusion, our experiments have provided insights into the synaptic mechanisms underlying the integration of inputs from Bar to autonomic circuitry in the lumbosacral spinal cord that may control micturition.

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