Journal of neurophysiology
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Paired-pulse transcranial magnetic stimulation (ppTMS) is a noninvasive method to measure cortical inhibition in vivo. Long interpulse interval (50-500 ms) ppTMS (LI-ppTMS) provokes intracortical inhibitory circuits and can reveal pathologically impaired cortical inhibition in disorders such as epilepsy. Adaptation of ppTMS protocols to rodent disease models is highly desirable to facilitate basic and translational research. ⋯ LI-ppTMS inhibition was reduced to as much as 53% of saline controls following PTZ injection, while spTMS-derived measures of corticospinal excitability were unchanged. Our data show that regional inhibition, similar to human LICI, is present in rats, can be elicited under PB or KAX anesthesia, and is reduced following convulsant administration. These results suggest a potential for LI-ppTMS as a biomarker of impaired cortical inhibition in murine disease models.
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Electrically excitable cells have voltage-dependent ion channels on the plasma membrane that regulate membrane permeability to specific ions. Voltage-gated Ca(2+) channels (VGCCs) are especially important as Ca(2+) serves as both a charge carrier and second messenger. Zebrafish (Danio rerio) are an important model vertebrate for studies of neuronal excitability, circuits, and behavior. ⋯ Application of GABA/baclofen or serotonin produced a voltage-dependent inhibition while application of the mu-opioid agonist DAMGO resulted in a voltage-independent inhibition. Unlike in mammalian neurons, GPCR-mediated voltage-dependent modulation of I(Ca) appears to be transduced primarily via a cholera toxin-sensitive Gα subunit. These results provide the basis for using the zebrafish model system to understanding Ca(2+) channel function, and in turn, how Ca(2+) channels contribute to mechanosensory function.
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The brain stem provides most of the noradrenaline (NA) present in the spinal cord, which functions to both increase spinal motoneuron excitability and inhibit sensory afferent transmission to motoneurons (excitatory postsynaptic potentials; EPSPs). NA increases motoneuron excitability by facilitating calcium-mediated persistent inward currents (Ca PICs) that are crucial for sustained motoneuron firing. Spinal cord transection eliminates most NA and accordingly causes an immediate loss of PICs and emergence of exaggerated EPSPs. ⋯ RX821001 had no effect in vitro even though it is an α(2) receptor inverse agonist. Our results suggest that after chronic spinal cord injury Ca PICs and spasms are facilitated, in part, by constitutive activity in α(1) adrenergic receptors. Additionally, peripherally derived NA (or similar ligand) activates both α(1) and α(2) adrenergic receptors, controlling PICs and EPSPs, respectively.
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TNFα induces mechanical sensitization of rat masseter muscle nociceptors, which takes 2-3 h to manifest and is mediated through activation of P55 and P75 receptors. This study was undertaken to determine whether TNFα induces nociceptor mechanical sensitization through the release of other algogenic substances such as glutamate, prostaglandin E(2) (PGE(2)), and/or nerve growth factor (NGF), which have been shown to induce mechanical sensitization of muscle nociceptors. Masseter muscle homogenate levels of PGE(2) and NGF were measured 3 h after injection of TNFα (1 μg) or vehicle control using commercially available kits. ⋯ Injection of diclofenac partially reversed the TNFα-induced decreases in the mechanical threshold (MT) of masseter muscle nociceptors, whereas vehicle control, APV, and TrkA antibody did not significantly alter nociceptor MT. These results suggest that TNFα-induced mechanical sensitization of masseter muscle nociceptors is mediated in part by increased PGE(2) levels. The findings of this study support the hypothesis that TNFα induces a delayed mechanical sensitization of masseter muscle nociceptors indirectly by the release of PGE(2).
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Phantom sensations and sensory hypersensitivity are disordered perceptions that characterize a variety of intractable conditions involving the somatosensory, visual, and auditory modalities. We report physiological correlates of two perceptual abnormalities in the auditory domain: tinnitus, the phantom perception of sound, and hyperacusis, a decreased tolerance of sound based on loudness. Here, subjects with and without tinnitus, all with clinically normal hearing thresholds, underwent 1) behavioral testing to assess sound-level tolerance and 2) functional MRI to measure sound-evoked activation of central auditory centers. ⋯ The results directly link hyperacusis and tinnitus to hyperactivity within the central auditory system. We hypothesize that the tinnitus-related elevations in cortical activation may reflect undue attention drawn to the auditory domain, an interpretation consistent with the lack of tinnitus-related effects subcortically where activation is less potently modulated by attentional state. The data strengthen, at a mechanistic level, analogies drawn previously between tinnitus/hyperacusis and other, nonauditory disordered perceptions thought to arise from neural hyperactivity such as chronic neuropathic pain and photophobia.