Articles: neuropathic-pain.
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Spinal nociception can be facilitated by 5-HT2 receptors in neuropathic pain. We investigated the involvement of glutamate receptors in dorsal neuron hyperexcitation that is promoted by 5-HT2B receptor (5-HT2BR) after spinal nerve ligation (SNL) in the rat. Augmentation of C-fiber-evoked potentials by spinal superfusion with 5-HT2BR agonist BW 723C86 in nerve-ligated rats was impeded by co-administration of NMDA receptor (NMDAR) antagonist D-AP5, but not by mGluR1/5 antagonist AIDA or mGluR2/3 antagonist LY 341495. ⋯ Chronic blockade of 5-HT2BR with selective antagonist SB 204741 after SNL bilaterally decreased the following: (i) PKCγ up-regulation in synaptic fraction, (ii) phosphorylation of NMDAR subunit NR1 (serine 889) in synaptic fraction, and (iii) co-localization of both PKCγ and phosphorylated NR1 with postsynaptic marker PSD-95. Chronic delivery of SB 204741 bilaterally attenuated thermal and mechanical allodynia occurring after SNL, particularly at day 2 post injury. These findings suggest that transient activation of the PKCγ/NMDAR pathway is critically involved in 5-HT2BR-mediated facilitation in the SNL model of neuropathic pain.
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Neuropathic pain resulting from spinal hemisection or selective spinal nerve ligation is characterized by an increase in membrane-bound tumor necrosis factor-alpha (mTNFα) in spinal microglia without detectable release of soluble TNFα (sTNFα). In tissue culture, we showed that a full-length transmembrane cleavage-resistant TNFα (CRTNFα) construct can act through cell-cell contact to activate neighboring microglia. We undertook the current study to test the hypothesis that mTNFα expressed in microglia might also affect the phenotype of primary sensory afferents, by determining the effect of CRTNFα expressed from COS-7 cells on gene expression in primary dorsal root ganglia (DRG) neurons. ⋯ Exposure to sTNFα produced an increase only in CCL2 expression and release. Treatment of the cells with an siRNA against tumor necrosis factor receptor 2 (TNFR2) significantly reduced CRTNFα-induced gene expression changes in DRG neurons, whereas administration of CCR2 inhibitor had no significant effect on CRTNFα-induced increase in gene expression and CCL2 release in DRG neurons. Taken together, the results of this study suggest that mTNFα expressed in spinal microglia can facilitate pain signaling by up-regulating the expression of cation channels and CCL2 in DRG neurons in a TNFR2-dependent manner.
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Neurorehabil Neural Repair · Sep 2013
Randomized Controlled Trial Comparative StudyEffect of single-session repetitive transcranial magnetic stimulation applied over the hand versus leg motor area on pain after spinal cord injury.
Neuropathic pain often follows spinal cord injury (SCI). ⋯ rTMS applied over the hand or leg motor cortex decreased neuropathic pain regardless of any change in cortical excitability, suggesting that the analgesic effect is not associated with local changes at the motor cortex level itself.
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SUMMARY Neuropathic pain is typically caused by a lesion or dysfunction in the nervous system that results in both negative (i.e., reduced sensitivity) and positive symptoms (i.e., paraesthesia, spontaneous ongoing pain with shooting, electric shock-like sensations and abnormal responses to evoked pain). Intriguingly, chronic pain disorders manifest profound alterations in brain structure and function, and thus, modern nuclear magnetic resonance (NMR) techniques have allowed us to begin to dissect the complexities of how neuropathic pain affects the brain. NMR approaches can be used as an independent measure to improve our understanding of key changes in brain structure, function and chemistry in chronic neuropathic pain. ⋯ Additionally, although at an early stage, NMR methods can also be useful to define clinical metrics to predict chronification of neuropathic pain and responses to drugs. This article provides a review of NMR techniques and their capacity to study spontaneous pain and evoked pain, as well as structural, functional and neurochemical alterations that have repeatedly been associated with chronic neuropathic pain. Finally, the importance for quantifying disease state and treatment efficacy in neuropathic pain using NMR techniques is discussed.
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Although hyperalgesia to mechanical stimuli is a frequent sign in patients with inflammation or neuropathic pain, there is to date no objective electrophysiological measure for its evaluation in the clinical routine. Here we describe a technique for recording the electroencephalographic (EEG) responses elicited by mechanical stimulation with a flat-tip probe (diameter 0.25 mm, force 128 mN). Such probes activate Aδ nociceptors and are widely used to assess the presence of secondary hyperalgesia, a psychophysical correlate of sensitization in the nociceptive system. ⋯ Such stimulation also resulted in a significant increase of the N-wave amplitude (+92.9%, P < 0.005), but not of the P wave (+6.6%, P = 0.61). In the patient, PEPs during stimulation of the hypoalgesic side were reduced. These results indicate that PEPs 1) reflect cortical activities triggered by somatosensory input transmitted in Aδ primary sensory afferents and spinothalamic projection neurons, 2) allow quantification of experimentally induced secondary mechanical hyperalgesia, and 3) have the potential to become a diagnostic tool to substantiate mechanical hyperalgesia in patients with presumed central sensitization.