Neuroscience letters
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Neuroscience letters · Mar 2014
Intrathecal carbenoxolone inhibits neuropathic pain and spinal wide-dynamic range neuronal activity in rats after an L5 spinal nerve injury.
Spinal glial gap junctions may play an important role in dorsal horn neuronal sensitization and neuropathic pain. In rats after an L5 spinal nerve ligation (SNL), we examined the effects of intrathecal injection of carbenoxolone (CBX), a gap junction decoupler, on neuropathic pain manifestations and on wide-dynamic range (WDR) neuronal activity in vivo. Intrathecal injection of CBX dose-dependently (0.1-50 μg, 10 μl) inhibited mechanical hypersensitivity in rats at 2-3 weeks post-SNL. ⋯ Further, rats did not develop tachyphylaxis to CBX-induced inhibition of mechanical hypersensitivity after repetitive drug treatments (25 μg/day) during days 14-16 post-SNL. Electrophysiological study in SNL rats showed that spinal topical application of CBX (100 μg, 50 μl), which mimics intrathecal drug administration, attenuated WDR neuronal responses to mechanical stimuli and to repetitive intracutaneous electrical stimuli (0.5 Hz) that induce windup, a short-form of activity-dependent neuronal sensitization. The current findings suggest that the inhibition of neuropathic pain manifestations by intrathecal injection of CBX in SNL rats may involve an inhibition of glial gap junctions and an attenuation of WDR neuronal activity in the dorsal horn.
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Neuroscience letters · Mar 2014
Clinical TrialPersonality dimensions and deep repetitive transcranial magnetic stimulation (DTMS) for treatment-resistant depression: a pilot trial on five-factor prediction of antidepressant response.
Prognostication is poor in repetitive transcranial magnetic stimulation (rTMS) treatment for major depressive disorder (MDD). Personality traits, particularly extraversion and neuroticism, have attracted increasing attention for both trait- and state-dependent characteristics in predicting response to pharmacotherapy, psychotherapy, and more recently to therapeutic neuromodulation for MDD. The advent of deep rTMS (DTMS) allows stimulation of deeper cortical regions, and we aimed to prospectively characterize personality dimensions and antidepressant response to DTMS in treatment-resistant MDD. ⋯ Five-factor personality assessment may have prognostic value in DTMS for resistant MDD. Agreeableness, extraversion, and conscientiousness are associated with decreases in depressive symptoms during treatment with DTMS.
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Neuroscience letters · Mar 2014
Discriminative and affective touch in human experimental tactile allodynia.
Recently, several studies have suggested a role for unmyelinated (C-tactile, CT) low-threshold mechanoreceptive afferents in the allodynic condition. In this psychophysical study we explored the integrity of both Aβ and CT afferent processing following application of the heat capsaicin model of tactile allodynia on the left forearm in healthy subjects (n=40). We measured tactile direction discrimination (TDD) to target the integrity of Aβ processing (n=20). ⋯ When comparing touch pleasantness in the allodynic and control zone, there was a significantly larger difference in ratings for CT targeted compared to CT suboptimal stimulation. The results suggest a disturbance in both Aβ-mediated discriminative and CT-mediated affective touch processing in human experimental tactile allodynia. Our findings support the canonical view that tactile allodynia is signaled by Aβ afferents but that CTs seem to contribute by the loss of a pain inhibiting role.
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Neuroscience letters · Mar 2014
The effects of different hyperbaric oxygen manipulations in rats after traumatic brain injury.
The protective effects of hyperbaric oxygenation following traumatic brain injury have been widely investigated; however, few studies have made systematic comparisons between the different hyperbaric oxygenation manipulations and their corresponding effects. In this study, male Sprague-Dawley rats were observed at 4h, 15d and 75d after traumatic brain injury. The effects of the different hyperbaric oxygenation manipulations on the rats were compared based on morphological, molecular biological and behavioral tests. ⋯ The effects observed in the hyperbaric oxygen-early group were better than the hyperbaric oxygen-delayed group, and the hyperbaric oxygen-early-delayed group demonstrated the best effects among all the groups. Our results showed the hyperbaric oxygenation was recommended early and delayed post-traumatic brain injury and exposure to hyperbaric oxygenation should be prolonged. These findings provide new ideal therapeutic insight for the clinical treatment of traumatic brain injury.
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Neuroscience letters · Mar 2014
Opioid and noradrenergic contributions of tapentadol in experimental neuropathic pain.
Tapentadol is a dual action molecule with mu opioid agonist and norepinephrine (NE) reuptake blocking activity that has recently been introduced for the treatment of moderate to severe pain. The effects of intraperitoneal (i.p.) morphine (10mg/kg), tapentadol (10 or 30 mg/kg) or duloxetine (30 mg/kg), a norepinephrine/serotonin (NE/5HT) reuptake inhibitor, were evaluated in male, Sprague-Dawley rats with spinal nerve ligation (SNL) or sham surgery. Additionally, the effects of these drugs on spinal cerebrospinal fluid (CSF) NE levels were quantified. ⋯ This could be detected 30 min following tapentadol (30 mg/kg) in both sham and SNL groups. Surprisingly, while the dose of morphine studied reversed tactile hypersensitivity in nerve-injured rats, CSF NE levels were significantly reduced in both sham- and SNL rats. The data suggest that tapentadol elicits enhanced elevation in spinal NE levels in a model of experimental neuropathic pain offering a mechanistic correlate to observed clinical efficacy in this pain state.