scholarly journals Gabapentin loses efficacy over time after nerve injury in rats

Pain ◽  
2016 ◽  
Vol 157 (9) ◽  
pp. 2024-2032 ◽  
Author(s):  
Masafumi Kimura ◽  
James C. Eisenach ◽  
Ken-ichiro Hayashida
Keyword(s):  
Pain ◽  
2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Carmen Camarena-Delgado ◽  
Meritxell Llorca-Torralba ◽  
Irene Suárez-Pereira ◽  
Lidia Bravo ◽  
Carolina López-Martín ◽  
...  

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Benjamin M. Davis ◽  
Li Guo ◽  
Nivedita Ravindran ◽  
Ehtesham Shamsher ◽  
Veerle Baekelandt ◽  
...  

AbstractIdentifying disease-specific patterns of retinal cell loss in pathological conditions has been highlighted by the emergence of techniques such as Detection of Apoptotic Retinal Cells and Adaptive Optics confocal Scanning Laser Ophthalmoscopy which have enabled single-cell visualisation in vivo. Cell size has previously been used to stratify Retinal Ganglion Cell (RGC) populations in histological samples of optic neuropathies, and early work in this field suggested that larger RGCs are more susceptible to early loss than smaller RGCs. More recently, however, it has been proposed that RGC soma and axon size may be dynamic and change in response to injury. To address this unresolved controversy, we applied recent advances in maximising information extraction from RGC populations in retinal whole mounts to evaluate the changes in RGC size distribution over time, using three well-established rodent models of optic nerve injury. In contrast to previous studies based on sampling approaches, we examined the whole Brn3a-positive RGC population at multiple time points over the natural history of these models. The morphology of over 4 million RGCs was thus assessed to glean novel insights from this dataset. RGC subpopulations were found to both increase and decrease in size over time, supporting the notion that RGC cell size is dynamic in response to injury. However, this study presents compelling evidence that smaller RGCs are lost more rapidly than larger RGCs despite the dynamism. Finally, using a bootstrap approach, the data strongly suggests that disease-associated changes in RGC spatial distribution and morphology could have potential as novel diagnostic indicators.


2013 ◽  
Vol 110 (7) ◽  
pp. 1663-1671 ◽  
Author(s):  
Hongmei Zhang ◽  
Haijun Zhang ◽  
Patrick M. Dougherty

Nerve injury-induced central sensitization can manifest as an increase in excitatory synaptic transmission and/or as a decrease in inhibitory synaptic transmission in spinal dorsal horn neurons. Cytokines such as tumor necrosis factor-α (TNF-α) are induced in the spinal cord under various injury conditions and contribute to neuropathic pain. In this study we examined the effect of TNF-α in modulating excitatory and inhibitory synaptic input to spinal substantia gelatinosa (SG) neurons over time in mice following chronic constriction injury (CCI) of the sciatic nerve. Whole cell patch-clamp studies from SG neurons showed that TNF-α enhanced overall excitability of the spinal cord early in time following nerve injury 3 days after CCI compared with that in sham control mice. In contrast, the effects of TNF were blunted 14 days after CCI in nerve-injured mice compared with sham surgery mice. Immunohistochemical staining showed that the expression of TNF-α receptor 1 (TNFR1) was increased at 3 days but decreased at 14 days following CCI in the ipsilateral vs. the contralateral spinal cord dorsal horn. These results suggest that TNF-α acting at TNFR1 is important in the development of neuropathic pain by facilitating excitatory synaptic signaling in the acute phases after nerve injury but has a reduced effect on spinal neuron signaling in the later phases of nerve injury-induced pain. Failure of the facilatory effects of TNF-α on excitatory synaptic signaling in the dorsal horn to resolve following nerve injury may be an important component in the transition between acute and chronic pain conditions.


2006 ◽  
Vol 10 (03) ◽  
pp. 131-140 ◽  
Author(s):  
Yasushi Morisawa ◽  
Shinichiro Takayama ◽  
Kazuhiko Okushi ◽  
Toshiyasu Nakamura ◽  
Keiichi Fukuda ◽  
...  

Peripheral nerve injury changes the kinetics of neurotrophins. The production of several neurotrophins increases at the site of injury. Although numerous reports have described changes in neurotrophins over time in areas of nerve injury, neurotrophin mRNA is present at very low levels in target tissues, making accurate quantitation difficult. We developed a reverse transcription–polymerase chain reaction/high-performance liquid chromatography (RT-PCR/HPLC) method that enables accurate quantitation of neurotrophin mRNA. We then attempted to quantitate mRNA levels for nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) produced by skeletal muscle innervated by the sciatic nerve following transection and reattachment of the nerve in mice. In addition, wet weights of the muscle were measured and changes in weight over time were determined. The results indicated that neurotrophin production in muscle increases as a result of peripheral nerve denervation due to transection, and decreases with nerve regeneration and reinnervation resulting from reattachment.


eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Margarita Calvo ◽  
Natalie Richards ◽  
Annina B Schmid ◽  
Alejandro Barroso ◽  
Lan Zhu ◽  
...  

Neuropathic pain following peripheral nerve injury is associated with hyperexcitability in damaged myelinated sensory axons, which begins to normalise over time. We investigated the composition and distribution of shaker-type-potassium channels (Kv1 channels) within the nodal complex of myelinated axons following injury. At the neuroma that forms after damage, expression of Kv1.1 and 1.2 (normally localised to the juxtaparanode) was markedly decreased. In contrast Kv1.4 and 1.6, which were hardly detectable in the naïve state, showed increased expression within juxtaparanodes and paranodes following injury, both in rats and humans. Within the dorsal root (a site remote from injury) we noted a redistribution of Kv1-channels towards the paranode. Blockade of Kv1 channels with α-DTX after injury reinstated hyperexcitability of A-fibre axons and enhanced mechanosensitivity. Changes in the molecular composition and distribution of axonal Kv1 channels, therefore represents a protective mechanism to suppress the hyperexcitability of myelinated sensory axons that follows nerve injury.


2021 ◽  
Vol 21 (2) ◽  
pp. 1259-1265
Author(s):  
Xuan Chen ◽  
Haiyang Zhao ◽  
Ye Li

At present, surgical suture treatment can be performed for spinal patients after nerve injury, but nerve regeneration and functional recovery require comprehensive treatment including drug treatment. However, there is still a lack of adjuvant therapeutic drugs that can effectively promote nerve regeneration and functional recovery. Drug treatment after nerve injury is the basis of nerve injury treatment and an important supplement to surgical treatment. Finding an effective method for treating spinal nerve injury and studying its mechanism of action may have important basic and clinical significance. The nanofiber catheter material simulates the nano/sub-micron level collagen fiber bundle structure of cells in the body, so it has been more and more widely used in the field of tissue engineering. Therefore, in this study, PHBV nanofiber catheter was successfully prepared by electrostatic spinning method, and the nanofiber catheter was characterized by SEM and DSC tests. The PHBV nanofiber catheter prepared by this research method has excellent characteristics such as porosity, large specific surface area, stable structure, thermal stability, and good mechanical properties. At the same time, adult male SD rats were selected to establish an animal model of cervical spine injury in this experiment. The expressions of three inflammation-related factors (IL-1α, IL-10 and TNF-1) were analyzed by ELISA. The results showed that in the spinal injury group, the expression of the three inflammatory factors all showed a significant increase over time and then reached a peak, then decreased and stabilized. This showed that the PHBV nanofiber catheter repairs cervical spine injury by affecting the inflammatory response, which is conducive to repairing cervical spine injury. RT-PCR was used to detect the expression of CNTF, GAP-43, and Tubulin-related proteins. During the neural regeneration process in rats, the expressions of both backbone proteins continued to be expressed, and they were first up-regulated and then flattened. This indicated that in the early stage of neural regeneration, a large number of skeletal proteins are synthesized, and they continue to be expressed at low levels over time, laying a foundation for the axon skeleton reconstruction.


2018 ◽  
Vol 41 ◽  
Author(s):  
David Hirshleifer ◽  
Siew Hong Teoh

AbstractEvolved dispositions influence, but do not determine, how people think about economic problems. The evolutionary cognitive approach offers important insights but underweights the social transmission of ideas as a level of explanation. The need for asocialexplanation for the evolution of economic attitudes is evidenced, for example, by immense variations in folk-economic beliefs over time and across individuals.


1988 ◽  
Vol 19 (3) ◽  
pp. 251-258 ◽  
Author(s):  
Virginia I. Wolfe ◽  
Suzanne D. Blocker ◽  
Norma J. Prater

Articulatory generalization of velar cognates /k/, /g/ in two phonologically disordered children was studied over time as a function of sequential word-morpheme position training. Although patterns of contextual acquisition differed, correct responses to the word-medial, inflected context (e.g., "picking," "hugging") occurred earlier and exceeded those to the word-medial, noninflected context (e.g., "bacon," "wagon"). This finding indicates that the common view of the word-medial position as a unitary concept is an oversimplification. Possible explanations for superior generalization to the word-medial, inflected position are discussed in terms of coarticulation, perceptual salience, and the representational integrity of the word.


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