Articles: neuralgia.
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Plasticity of inhibitory transmission in the spinal dorsal horn (SDH) is believed to be a key mechanism responsible for pain hypersensitivity in neuropathic pain syndromes. We evaluated this plasticity by recording responses to mechanical stimuli in silent neurons (nonspontaneously active [NSA]) and neurons showing ongoing activity (spontaneously active [SA]) in the SDH of control and nerve-injured mice (cuff model). The SA and NSA neurons represented 59% and 41% of recorded neurons, respectively, and were predominantly wide dynamic range (WDR) in naive mice. ⋯ Pharmacological blockade of spinal inhibition with a mixture of GABAA and glycine receptor antagonists significantly increased responses to innocuous mechanical stimuli in SA and NSA neurons from sham animals, but had no effect in sciatic nerve-injured animals, revealing a dramatic loss of spinal inhibitory tone in this situation. Moreover, in nerve-injured mice, local spinal administration of acetazolamide, a carbonic anhydrase inhibitor, restored responses to touch similar to those observed in naive or sham mice. These results suggest that a shift in the reversal potential for anions is an important component of the abnormal mechanical responses and of the loss of inhibitory tone recorded in a model of nerve injury-induced neuropathic pain.
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Am J Hosp Palliat Care · Jul 2016
Observational StudyThe Prevalence of Neuropathic Pain in Terminally Ill Patients With Cancer Admitted to a Palliative Care Unit: A Prospective Observational Study.
The primary aim of this study was to determine the prevalence of neuropathic pain (NP) in patients with cancer receiving palliative care. ⋯ The prevalence of NP in terminally ill patients with cancer in Japanese palliative care units was 18.6%.
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Neurobiology of disease · Jul 2016
Reversal of neurochemical alterations in the spinal dorsal horn and dorsal root ganglia by Mas-related gene (Mrg) receptors in a rat model of spinal nerve injury.
The rodent Mas-related gene (Mrg) receptor subtype C has been demonstrated to inhibit pathological pain. This study investigated the mechanisms underlying the reversal of pain hypersensitivity by the selective MrgC receptor agonist bovine adrenal medulla 8-22 (BAM8-22) in a rat model of L5 spinal nerve ligation (SNL). Intrathecal (i.t.) administration of BAM8-22 (0.1-10nmol) attenuated mechanical allodynia in a dose-dependent manner on day 10 after SNL. ⋯ Furthermore, the BAM8-22 exposure suppressed the lipopolysaccharide (LPS)-induced increase of nNOS and IL-1β in the DRG explant cultures and the BAM8-22-induced suppression disappeared in the presence of MrgC receptor antibody. The present study provides evidence that activation of MrgC receptors inhibits nerve injury-induced increase of pronociceptive molecules in DRG neurons, suppressing astrocyte activation, the upregulation of excitatory mediators and phosphorylation of transcription factors in the spinal dorsal horn. As MrgC receptors are unequally expressed in the dorsal root and trigeminal ganglia, this study suggests that targeting MrgC receptors could be a new therapy for neuropathic pain with limited unwanted effects.
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Neuropathic pain represents a substantial clinical challenge; understanding the underlying neural mechanisms and back-translation of therapeutics could aid targeting of treatments more effectively. The ventral posterior thalamus (VP) is the major termination site for the spinothalamic tract and relays nociceptive activity to the somatosensory cortex; however, under neuropathic conditions, it is unclear how hyperexcitability of spinal neurons converges onto thalamic relays. This study aimed to identify neural substrates of hypersensitivity and the influence of pregabalin on central processing. ⋯ Additionally, WDR, but not NS, neurons in SNL rats exhibited substantially higher rates of spontaneous firing, which may correlate with ongoing pain. The ratio of WDR-to-NS neurons was comparable between SNL and naive/sham groups, suggesting relatively few NS neurons gain sensitivity to low-intensity stimuli leading to a "WDR phenotype." After neuropathy was induced, the proportion of cold-sensitive WDR and NS neurons increased, supporting the suggestion that changes in frequency-dependent firing and population coding underlie cold hypersensitivity. In SNL rats, pregabalin inhibited mechanical and heat responses but not cold-evoked or elevated spontaneous activity.
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Matrix metalloproteinase (MMPs) and endothelin-1 may prove to be important in the generation of pain induced by inflammation and nerve lesion. This study aimed to investigate the relationship between endothelin receptors and MMPs. ⋯ In this study, CGS-26303 can attenuate SNL-induced neuropathic pain by down-regulating MMP-9, MMP-2, and ETAR expressions in the DRG and by glia cell activation in the SDH.