Articles: neuralgia.
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Data from preclinical research have been suggested to suffer from a lack of inherent reproducibility across laboratories. The goal of our study was to replicate findings from a previous report that demonstrated positive effects of Meteorin, a novel neurotrophic factor, in a rat model of neuropathic pain induced by chronic constriction injury (CCI). Notably, 5 to 6 intermittent subcutaneous (s.c.) injections of Meteorin had been reported to produce reversal of mechanical allodynia/thermal hyperalgesia after injury, wherein maximum efficacy of Meteorin was reached slowly and outlasted the elimination of the compound from the blood by several weeks. ⋯ Systemic administration of recombinant mouse Meteorin (0.5 and 1.8 mg/kg, s.c.) at days 10, 12, 14, 17, and 19 after CCI produced a prolonged reversal of neuropathic hypersensitivity with efficacy comparable with that obtained with gabapentin (100 mg/kg, orally). Despite some protocol deviations (eg, nociceptive endpoint, animal vendor, testing laboratory, investigator, etc.) being incurred, these did not affect study outcome. By paying careful attention to key facets of study design, using bioactive material, and confirming drug exposure, the current data have replicated the salient findings of the previous study, promoting confidence in further advancement of this novel molecule as a potential therapy for neuropathic pain.
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High voltage-activated (HVA) Ca2+ (CaV) channels are oligomeric complexes formed by an ion-conducting main subunit (Cavα1) and at least two auxiliary subunits (Cavβ and CaVα2δ). It has been reported that the expression of CaVα2δ1 increases in the dorsal root ganglia (DRGs) of animals with mechanical allodynia, and that the transcription factor Sp1 regulates the expression of the auxiliary subunit. Hence, the main aim of this work was to investigate the role of Sp1 as a molecular determinant of the exacerbated expression of CaVα2δ-1 in the nerve ligation-induced model of mechanical allodynia. ⋯ Interestingly, intrathecal administration of the Sp1 inhibitor mithramycin A (Mth) prevented allodynia and decreased the expression of Sp1 and CaVα2δ-1. Likewise, electrophysiological recordings showed that incubation with Mth decreased Ca2+ current density in the DRG neurons, acting mostly on HVA channels. These results suggest that L5/L6 SNL produces mechanical allodynia and increases the expression of the transcription factor Sp1 and the subunit CaVα2δ-1 in the DRGs, while Mth decreases mechanical allodynia and Ca2+ currents through HVA channels in sensory neurons by reducing the functional expression of the CaVα2δ-1 subunit.
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J. Endocrinol. Invest. · Aug 2019
Hypothalamic-pituitary-adrenal axis function in traumatic spinal cord injury-related neuropathic pain: a case-control study.
This study aimed to investigate the hypothalamic-pituitary-adrenal (HPA) axis in spinal cord injury (SCI)-related neuropathic pain (NP) using dynamic adrenocorticotropic hormone (ACTH) stimulation tests. ⋯ This study demonstrated that, in chronic SCI patients with NP, basal cortisol levels are relatively higher compared to healthy controls, and that HPA axis can be activated with low- and standard-dose ACTH stimulation tests. Although NP following SCI was not significantly associated with hypo- or hypercortisolemia, either after low- or standard-dose ACTH stimulation test, the severity of NP during chronic SCI may be positively associated with HPA axis activity.
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The present study investigated the role of the amygdala N-methyl-d-aspartate (NMDA) receptors/nitric oxide synthase pathway in morphine-induced anti-allodynia. Concurrently with the bilateral cannulation of the central amygdala, chronic constriction of the sciatic nerve was performed on male Wistar rats. Morphine (3-5 mg/kg) was administered intraperitoneally to induce anti-allodynia. ⋯ PERSPECTIVE: Neuropathic pain is difficult to treat and the exact mechanisms remain unknown. This article suggests the importance of the amygdala glutamatergic and nitric oxide systems in morphine-induced anti-allodynia. These findings might be used in clinical studies to reach a better understanding of neuropathic pain mechanisms and treatment.