Articles: neuropathic-pain.
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Annexin A2 (ANX2) is a calcium (Ca(2+))-binding protein that binds to acidic phospholipids and is known to play a crucial role in many cellular regulatory processes. In particular, ANX2 has been described as a crucial receptor for thrombolysis by the tissue-type plasminogen activator (tPA) and plasmin system. In the nervous system, tPA is involved in processes of neuronal plasticity such as hippocampal long-term potentiation (LTP) and in the dorsal horn pain in several pain models. ⋯ Double-labeling analysis revealed the co-localization of ANX2 with tPA in the axons of primary afferents in the dorsal horn. Experimental inhibition of ANX2 and tPA interaction by intrathecal administration of homocysteine significantly prevented and reversed SNI-induced mechanical allodynia. Thus, alterations of ANX2 may be involved in tPA-dependent plasticity after peripheral nerve injury and have an important role in neuropathic pain.
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We investigated functional alterations of voltage-gated calcium channels (VGCCs) in excitatory synaptic transmission from primary afferent A- and C-fibers after peripheral nerve injury. Patch-clamp recordings were performed on substantia gelatinosa (SG) neurons of spinal cord slices with an attached dorsal root, prepared from L5 spinal nerve-ligated (SNL) rats. The effects of neuronal VGCC blockers, ω-conotoxin GVIA (ω-CgTX) for N-type channels and ω-agatoxin IVA (ω-AgaIVA) for P/Q-type channels, on evoked excitatory postsynaptic currents (eEPSCs) by stimulation of A- or C-fibers were studied. ⋯ In terms of A-fiber eEPSCs, ω-CgTX elicited similar inhibition in nerve-injured and sham-operated rats. ω-AgaIVA (0.1μM) had less effect on A- or C-fiber eEPSCs. These results indicate that N-type, but not P/Q-type, VGCCs mainly contribute to excitatory synaptic transmission from A- and C-fibers in the spinal dorsal horn. More importantly, following nerve injury, the functional contribution of N-type VGCCs to nociceptive transmission is increased in the pre-synaptic terminals of injured C-fibers.
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Here we studied whether and through which mechanisms spinal administration of histamine dihydrochloride (histamine) attenuates pain behavior in neuropathic animals. Experiments were performed in rats with spinal nerve ligation-induced neuropathy and a chronic intrathecal catheter for spinal drug delivery. Mechanical hypersensitivity was assessed with monofilaments while radiant heat was used for assessing nociception. ⋯ Additionally, histamine prevented central (presumably postsynaptically-induced) facilitation of hypersensitivity induced by N-methyl-d-aspartate. The results indicate that spinal histamine at the dose range of 0.1-10µg selectively attenuates mechanical hypersensitivity and ongoing pain in neuropathy. The spinal histamine-induced antihypersensitivity effect involves histamine H2 and GABA(A) receptors and (presumably neuropathy-induced) co-activation of spinal α1-adrenoceptors.
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Upper extremity neuropathic pain states greatly impact patient functionality and quality of life, despite appropriate surgical intervention. This article focuses on the advanced therapies that may improve pain care, including advanced treatment strategies that are available. The article also surveys therapies on the immediate horizon, such as spinal cord stimulation, peripheral nerve stimulation, and dorsal root ganglion spinal cord stimulation. As these therapies evolve, so too will their placement within the pain care algorithm grounded by a foundation of evidence to improve patient safety and management of patients with difficult neuropathic pain.
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The treatment of neuropathic pain by neuromodulation is an objective for more than 40 years in modern clinical practice. With respect to spinal cord and deep brain structures, the cerebral cortex is the most recently evaluated target of invasive neuromodulation therapy for pain. In the early 90s, the first successes of invasive epidural motor cortex stimulation (EMCS) were published. ⋯ It is therefore important to know the principles and to assess the merit of these techniques on the basis of a rigorous assessment of the results, to avoid fad. Various types of chronic neuropathic pain syndromes can be significantly relieved by EMCS or repeated daily sessions of high-frequency (5-20 Hz) rTMS or anodal tDCS over weeks, at least when pain is lateralized and stimulation is applied to the motor cortex contralateral to pain side. However, cortical stimulation therapy remains to be optimized, especially by improving EMCS electrode design, rTMS targeting, or tDCS montage, to reduce the rate of nonresponders, who do not experience clinically relevant effects of these techniques.