Articles: peripheral-nerve-injuries-physiopathology.
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To gain insight into the epigenetic regulation of CC-chemokine ligand (CCL) 2 and CCL3, key players in the peripheral sensitization leading to neuropathic pain, we examined the relationship between histone H3 modification and the upregulation of these molecules using a mouse model of neuropathic pain after partial sciatic nerve ligation (PSL). We found that circuiting bone marrow (BM)-derived macrophages infiltrated into the injured sciatic nerve (SCN) using enhanced green fluorescent protein chimeric mice. The mRNA levels of CCL2, CCL3 and their receptors (CCR2 and CCR1/CCR5, respectively) were increased in the injured SCN. ⋯ Furthermore, upregulation of CCLs and CCRs were suppressed by histone acetyltransferase inhibitor, anacardic acid. Taken together, our findings demonstrate that CCL2 and CCL3 are upregulated in the injured peripheral nerve through epigenetic histone modification in infiltrating immune cells such as macrophages. These chemokine cascades may subsequently elicit chronic neuroinflammation following nerve injury.
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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. ⋯ 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.
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J Biomed Nanotechnol · Jun 2013
Fabrication of seamless electrospun collagen/PLGA conduits whose walls comprise highly longitudinal aligned nanofibers for nerve regeneration.
An ideal nerve scaffold should supply structural guidance and trophic support to facilitate nerve regeneration. Aligned electrospun nanofibers have shown considerable promise for the precise guidance of regenerating axons in vitro and in vivo. Therefore, uniaxially aligned three-dimension (3D) nanofiberous scaffolds may allow regenerating axons to traverse large gaps to treat severe nerve injuries. ⋯ To test the effectiveness of these scaffolds at restoring neuronal connections, they were implanted into adult rats across a 13 mm sciatic nerve defect. Tests of, motor function, nerve conduction, axonal and Schwann cell morphology, and marker expression all revealed that uniaxially aligned seamless 3D electrospun collagen/PLGA NCs were superior to randomly oriented NCs and inferior to autografts for promoting axon regeneration, myelination, action potential propagation, neuromuscular transmission, and functional recovery. These uniaxially aligned seamless 3D electrospun collagen/PLGA nerve guides can also incorporate signaling molecules and additional structural cues to guide nerve growth, and so may be a promising substitute for autogenous nerve grafts.
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Biochem. Biophys. Res. Commun. · May 2013
Nerve injury-induced upregulation of miR-21 in the primary sensory neurons contributes to neuropathic pain in rats.
Neuropathic pain is intractable chronic pain caused by damage to the somatosensory system. Peripheral nerve injury of the primary sensory neurons changes expressions of multiple microRNAs that affect many aspects of cellular functions by regulating specific gene expressions. miR-21, a well-characterized oncogenic miRNA, is consistently upregulated after peripheral nerve injury in the dorsal root ganglion (DRG), where cell bodies of primary sensory neurons exist. However, their causal relationship to the pain is fully unknown. ⋯ Intrathecal administration of interleukin-1β also increased the miR-21 expression in the DRG. Both mechanical allodynia and thermal hyperalgesia in the neuropathic pain were attenuated by intrathecal administration of miR-21 inhibitor. miR-21 is specifically upregulated in the injured DRG neurons and causally involved in the late phase of neuropathic pain. Therefore, miR-21 and its modulatory system may be a therapeutic target for intractable chronic neuropathic pain.
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The treatment of global brachial plexus avulsion is a demanding field of hand and upper extremity surgery. The recent development of functional and quality-of-life (QOL) assessment tools has improved quantifying these functional outcomes after surgery. ⋯ This study validated the effect of nerve transfers for global brachial plexus avulsions from objective MRC grading combining with patients' self-assessments. Neurolysis after neurotisations correlated positively with functional outcomes.