Experimental neurology
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Experimental neurology · May 2014
Assessment of sensory thresholds and nociceptive fiber growth after sciatic nerve injury reveals the differential contribution of collateral reinnervation and nerve regeneration to neuropathic pain.
Following traumatic peripheral nerve injury reinnervation of denervated targets may be achieved by regeneration of injured axons and by collateral sprouting of neighbor undamaged axons. Experimental models commonly use sciatic nerve injuries to assess nerve regeneration and neuropathic pain, but behavioral tests for evaluating sensory recovery often disregard the pattern of hindpaw innervation. This may lead to confounding attribution of recovery of sensory responses to improvement in sciatic nerve regeneration instead of collateral reinnervation by the undamaged saphenous nerve. ⋯ On the other side, late sciatic hyperalgesia was accompanied by gradual skin reinnervation after 4weeks. The standardization of algesimetry testing in sciatic nerve injury models, as proposed in this study, provides a suitable model for studying in parallel neuropathic pain and sensory nerve regeneration processes. Our results also indicate that collateral sprouting and axonal regeneration contribute differently in the initiation and maintenance of neuropathic pain.
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Experimental neurology · May 2014
Activation of spinal phosphatidylinositol 3-kinase/protein kinase B mediates pain behavior induced by plantar incision in mice.
The etiology of postoperative pain may be different from antigen-induced inflammatory pain and neuropathic pain. However, central neural plasticity plays a key role in incision pain. It is also known that phosphatidylinositol 3-kinase (PI3K) and protein kinase B/Akt (PKB/Akt) are widely expressed in laminae I-IV of the spinal horn and play a critical role in spinal central sensitization. ⋯ Pre-treatment with PI3K inhibitors, wortmannin or LY294002 prevented the activation of Akt brought on by plantar incision in a dose-dependent manner. In addition, inhibition of spinal PI3K signaling pathway prevented pain behaviors (dose-dependent) and spinal Fos protein expression caused by plantar incision. These data demonstrated that PI3K signaling mediated pain behaviors caused by plantar incision in mice.
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Experimental neurology · May 2014
Acute exercise prevents the development of neuropathic pain and the sprouting of non-peptidergic (GDNF- and artemin-responsive) c-fibers after spinal cord injury.
Spinal cord injury (SCI) impaired sensory fiber transmission leads to chronic, debilitating neuropathic pain. Sensory afferents are responsive to neurotrophic factors, molecules that are known to promote survival and maintenance of neurons, and regulate sensory neuron transduction of peripheral stimuli. A subset of primary afferent fibers responds only to the glial cell-line derived neurotrophic factor (GDNF) family of ligands (GFLs) and is non-peptidergic. ⋯ Importantly, in SCI rats that received Ex, the incidence of tactile allodynia decreased to 7% (1/17) and there was maintenance of GDNF and artemin at normal levels, with a normal distribution of GFL-responsive fibers. These data suggest that GFLs and/or their downstream effectors may be important modulators of pain fiber plasticity, representing effective targets for anti-allodynic therapeutics. Furthermore, we highlight the potent beneficial effects of acute exercise after SCI.
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Experimental neurology · May 2014
Coupling of serotonergic input to NMDA receptor-phosphorylation following peripheral nerve injury via rapid, synaptic up-regulation of ND2.
Evidence implicates serotonergic input to spinal dorsal horn neurons in shifting the NMDA receptor (NMDAR) into a high functional output profile after spinal nerve ligation (SNL). We investigated the involvement of adaptor protein NADH dehydrogenase subunit 2 (ND2) in NMDAR-phosphorylation and spinal hyperexcitability secondary to peripheral nerve injury. Immunofluorescence for ND2 was found in dorsal horn neurons immunopositive for NMDAR subunit NR1. ⋯ Rotenone also abolished enhancement of evoked potentials induced by simultaneous stimulation of NMDA and 5-HR2B receptors in uninjured rats. Increased postsynaptic up-regulation of ND2/pNMDAR 60min after SNL was prevented by prior administration of selective 5-HT2B antagonist SB204741. These results support a pivotal role for ND2 in coupling serotonergic input to NMDAR-activation during neuropathic pain.
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Experimental neurology · Apr 2014
Randomized Controlled TrialDecision-making under risk is improved by both dopaminergic medication and subthalamic stimulation in Parkinson's disease.
Inconsistent findings regarding the effects of dopaminergic medication (MED) and deep brain stimulation (DBS) of the subthalamic nucleus (STN) on decision making processes and impulsivity in Parkinson's disease (PD) patients have been reported. This study investigated the influence of MED and STN-DBS on decision-making under risk. Eighteen non-demented PD patients, treated with both MED and STN-DBS (64.3±10.2years, UPDRS III MED off, DBS off 45.5±17.1) were tested with the Game of Dice Task (GDT) which probes decision-making under risk during four conditions: MED on/DBS on, MED on/DBS off, MED off/DBS on, and MED off/DBS off. ⋯ Significantly higher GDT net scores were observed in Med on in contrast to Med off conditions as well as in DBS on versus DBS off conditions. However, no effect of therapy for the patient's ability to make use of negative feedback could be detected. The data suggest a positive influence of both MED and STN-DBS on making decisions under risk in PD patients, an effect which seems to be mediated by mechanisms other than the use of negative feedback.