Neuroscience
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In this study, we evaluated whether astrocytic and microglial activation mediates below-level neuropathic pain following spinal cord injury. Male Sprague-Dawley (225-250 g) rats were given low thoracic (T13) spinal transverse hemisection and behavioral, electrophysiological and immunohistochemical methods were used to examine the development and maintenance of below-level neuropathic pain. On postoperation day 28, both hind limbs showed significantly decreased paw withdrawal thresholds and thermal latencies as well as hyperexcitability of lumbar (L4-5) spinal wide dynamic range (WDR) neurons on both sides of spinal dorsal horn compared to sham controls (* P<0.05). ⋯ In electrophysiological studies, topical treatment of 10 mM PPF onto the spinal surface attenuated the neuronal hyperexcitability in response to mechanical stimuli. In immunohistochemical studies, astrocytes and microglia in rats with spinal hemisection showed significantly increased GFAP and OX-42 expression in both superficial and deep dorsal horns in the lumbar spinal dorsal horn compared to sham controls (* P<0.05) that was prevented in a dose-related manner by PPF. In conclusion, our present data support astrocytic and microglial activation that contributes to below-level central neuropathic pain following spinal cord injury.
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Neurogenic inflammation of the dura mater encephali has been suggested to contribute to the mechanisms of meningeal nociception and blood flow regulation. Recent findings demonstrated that the rat dura mater is innervated by trigeminal capsaicin-sensitive peptidergic nociceptive afferent nerves which mediate meningeal vascular responses through activation of the transient receptor potential vanilloid type 1 (TRPV1) receptor. The present work explored the functional significance of the capsaicin-sensitive subpopulation of dural afferent nerves via their contribution to the meningeal vascular responses evoked through activation of the proteinase-activated receptor 2 (PAR-2). ⋯ The vasodilator responses elicited by very low concentrations of capsaicin (10 nM) were significantly enhanced by prior application of SLIGRL-NH(2). The present findings demonstrate that activation of the PAR-2 localized on capsaicin-sensitive trigeminal nociceptive afferent nerves induces vasodilatation in the dural vascular bed by mechanisms involving NO and CGRP release. The results indicate that the PAR-2-mediated activation and sensitization of meningeal capsaicin-sensitive C-fiber nociceptors may be significantly implicated in the pathophysiology of headaches.
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There is developmental refinement of the proprioreceptive muscle afferent input to the rat ventral horn. This study explored the extent to which this occurs in the medulla. Muscle afferents were transganglionically labeled from the extensor digitorum communis forelimb muscle with cholera toxin B subunit. ⋯ There was a statistically significant, approximately 40% reduction in the number of muscle afferent boutons in the cuneate nucleus during this developmental period. Previous studies suggest that perturbations to the corticospinal input during a developmental critical period influence the eventual size of the muscle afferent input to the ventral horn. Corticocuneate fibers invade the nucleus during the same period and may influence reorganization of its muscle afferent input, making it another potential site for aberrant reflex development in cerebral palsy.
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Forced choice between alternative options of unpredictable outcome is a complex task that requires continual update of the value associated with each option. Prefrontal areas such as the orbitofrontal cortex (OFC) have been shown to play a major role in performance on ambiguous decision-making tasks with substantial risk component, broadly named as "gambling tasks." We have recently demonstrated that rats display complex decision-making behavior in a rodent gambling task based on serial choices between rewards of different value and probability. This rodent task retains many of the key characteristics of the human Iowa Gambling Task (IGT), and performance in this novel task is also disrupted by OFC or amygdalar lesioning. ⋯ We found that animals with a monoarthritic inflammatory model of chronic pain systematically preferred the lever associated with larger but infrequent rewards. In addition, we measured the neurochemical content of the OFC, amygdala and nucleus accumbens using HPLC, and found that in prolonged chronic pain animals there was a decrease in the tonic levels of dopamine, DOPAC (3,4-hydroxyphenyl-acetic acid) and 5-HIAA (5-hydroxyindole-3-acetic acid) in the OFC. This is the first report of the effect of chronic pain in rat decision-making processes and supports the notion that pain may have profound effects on the functioning of the reward-aversion circuitry relevant to strategic planning.
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It has been long known that the physiological concentrations of polyamines putrescine, spermidine and spermine are essential for cell growth. However, the role of endogenous polyamines in behavior function is poorly understood at present. This study investigated animals' behavioral performance and neurochemical changes in the hippocampus and prefrontal cortex following i.c.v. microinfusion of difluoromethylornithine (DFMO), a potent inhibitor of putrescine synthesis. ⋯ These results demonstrate that acute depletion of putrescine by DFMO produces anxiety-like behavior and impairs memory for the object displacement without affecting animals' locomotor and exploratory activity and spatial learning and memory. Multiple regression analysis data suggest the different roles of endogenous putrescine, spermidine and spermine on behavior function. The spermidine/spermine and glutamate/GABA ratios in hippocampal DG are strongly associated with anxiety-like behavior in the DFMO rats.