1,009 research outputs found
Multiple sites and actions of gabapentin-induced relief of ongoing experimental neuropathic pain
Gabapentin is a first-line therapy for neuropathic pain but its mechanisms and sites of action
remain uncertain. We investigated gabapentin-induced modulation of neuropathic pain following
spinal nerve ligation (SNL) in rats. Intravenous or intrathecal gabapentin reversed evoked
mechanical hypersensitivity, produced conditioned place preference (CPP) and dopamine release
in the nucleus accumbens (NAc) selectively in SNL rats. Spinal gabapentin also significantly
inhibited dorsal horn wide dynamic range (WDR) neuronal responses to a range of evoked stimuli
in SNL rats. In contrast, gabapentin microinjected bilaterally into the rostral anterior cingulate
cortex (rACC), produced CPP and elicited NAc dopamine release selectively in SNL rats but did
not reverse tactile allodynia and had marginal effects on WDR neuronal activity. Moreover,
blockade of endogenous opioid signaling in the rACC prevented intravenous gabapentin-induced
CPP and NAc dopamine release but failed to block its inhibition of tactile allodynia. Gabapentin
therefore can potentially act to produce its pain relieving effects by (a) inhibition of injury-induced
spinal neuronal excitability, evoked hypersensitivity and ongoing pain and (b) selective supraspinal
modulation of affective qualities of pain, without alteration of reflexive behaviors. Consistent with
previous findings of pain relief from non-opioid analgesics, gabapentin requires engagement of
rACC endogenous opioid circuits and downstream activation of mesolimbic reward circuits
reflected in learned pain motivated behaviors. These findings support the partial separation of
sensory and affective dimensions of pain in this experimental model and suggest that modulation
of affective-motivational qualities of pain may be the preferential mechanism of gabapentin’s
analgesic effects in patients
Selective deficiencies in descending inhibitory modulation in neuropathic rats: implications for enhancing noradrenergic tone
Pontine noradrenergic neurones form part of a descending inhibitory system that influences spinal nociceptive processing. Weak or absent descending inhibition is a common feature of chronic pain patients. We examined the extent to which the descending noradrenergic system is tonically active, how control of spinal neuronal excitability is integrated into thalamic relays within sensory-discriminative projection pathways, and how this inhibitory control is altered after nerve injury. In vivo electrophysiology was performed in anaesthetised spinal nerve–ligated (SNL) and sham-operated rats to record from wide dynamic range neurones in the ventral posterolateral thalamus (VPL). In sham rats, spinal block of α2-adrenoceptors with atipamezole resulted in enhanced stimulus-evoked and spontaneous firing in the VPL, and produced conditioned place avoidance. However, in SNL rats, these conditioned avoidance behaviours were absent. Furthermore, inhibitory control of evoked neuronal responses was lost, but spinal atipamezole markedly increased spontaneous firing. Augmenting spinal noradrenergic tone in neuropathic rats with reboxetine, a selective noradrenergic reuptake inhibitor, modestly reinstated inhibitory control of evoked responses in the VPL but had no effect on spontaneous firing. By contrast, clonidine, an α2 agonist, inhibited both evoked and spontaneous firing, and exhibited increased potency in SNL rats compared with sham controls. These data suggest descending noradrenergic inhibitory pathways are tonically active in sham rats. Moreover, in neuropathic states, descending inhibitory control is diminished, but not completely absent, and distinguishes between spontaneous and evoked neuronal activity. These observations may have implications for how analgesics targeting the noradrenergic system provide relief
MCMAS: an open-source model checker for the verification of multi-agent systems
We present MCMAS, a model checker for the verification of multi-agent systems. MCMAS supports efficient symbolic techniques for the verification of multi-agent systems against specifications representing temporal, epistemic and strategic properties. We present the underlying semantics of the specification language supported and the algorithms implemented in MCMAS, including its fairness and counterexample generation features. We provide a detailed description of the implementation. We illustrate its use by discussing a number of examples and evaluate its performance by comparing it against other model checkers for multi-agent systems on a common case study
Observation of CR Anisotropy with ARGO-YBJ
The measurement of the anisotropies of cosmic ray arrival direction provides
important informations on the propagation mechanisms and on the identification
of their sources. In this paper we report the observation of anisotropy regions
at different angular scales. In particular, the observation of a possible
anisotropy on scales between 10 and 30
suggests the presence of unknown features of the magnetic fields the charged
cosmic rays propagate through, as well as potential contributions of nearby
sources to the total flux of cosmic rays. Evidence of new weaker few-degree
excesses throughout the sky region R.A. is
reported for the first time.Comment: Talk given at 12th TAUP Conference 2011, 5-9 September 2011, Munich,
German
Study on Composition Distribution and Ferromagnetism of Monodisperse FePt Nanoparticles
Monodisperse FePt nanoparticles with size of 4.5 and 6.0 nm were prepared by simultaneous reduction of platinum acetylacetonate and thermal decomposition of iron pentacarbonyl in benzylether. The crystallography structure, size, and composition of the FePt nanoparticles were examined by X-ray diffraction and transmission electron microscopy. Energy dispersive X-ray spectrometry measurements of individual particles indicate a broad compositional distribution in both the 4.5 and 6 nm FePt nanoparticles. The effects of compositional distribution on the phase-transition and magnetic properties of the FePt nanoparticles were investigated
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