Neuroscience
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Chronic muscle pain is acutely worsened by exercise. Acid sensing ion channels (ASIC) are heteromeric channels expressed in muscle sensory neurons that detect decreases in pH. We have previously shown ASIC3 is important in activity-induced hyperalgesia. ⋯ There was a significant leftward shift in the pH dose response of steady-state desensitization and decrease in pH-evoked current amplitudes. These results suggest that blockade of ASIC1a modulates the kinetics of heteromeric ASICs to prevent development of activity-induced hyperalgesia. These data suggest ASIC1a is a key subunit in heteromeric ASICs and may be a pharmacological target for treatment of musculoskeletal pain.
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Action observation is known to enhance sensorimotor system activation, and such effect has been linked to neural priming and response facilitation mechanisms. This facilitation effect, however, has been primarily studied by focusing on high-level motor proficiency, whereas evidence on the effect of observing poorly performed actions is still lacking. We then devised a study to investigate neural correlates of the observation of suboptimal motor acts as mirrored by corticospinal activation (via transcranial magnetic stimulation (TMS), Experiment 1) and by modulation of cortical oscillatory activity (via electroencephalography (EEG), Experiment 2). 40 participants were presented with four randomly reiterated videos. ⋯ Analyses highlighted both increased corticospinal excitability and desynchronized alpha-beta oscillations during the observation of poorly performed motor acts performed by the mildly impaired MS patient. Further, we observed gradually increasing beta activity across videos reiterations, specifically for the minimally impaired patient's video. Reported findings corroborate the hypotheses that the action-observation network and the motor system might be involved in processes evoked in the attempt to understand and predict observed actions which do not belong to the onlookers' motor repertoire, reflecting in an increased sensorimotor activity.
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In DRG an increase in miR-133b-3p, miR-143-3p, and miR-1-3p correlates with the lack of development of neuropathic pain following a peripheral nerve injury. Using lentiviral (LV) vectors we found that a single injection of LV-miR-133b-3p or LV-miR-143-3p immediately after a peripheral nerve injury prevented the development of sustained mechanical and cold allodynia. Injection of LV-miR-133b-3p or LV-miR-143-3p by themselves or in combination, on day 3 post-injury produced a partial and transient reduction in mechanical allodynia and a sustained decrease in cold allodynia. ⋯ LV-miR133b-3p and LV-miR-143-3p reduced TRPM8-mRNA. LV-miR-133b-3p and LV-miR-143-3p prevent the development of chronic pain when injected immediately after the injury, but are only partially effective when injected at later times. LV-miR-1a-3p had no effect on pain, but complemented the actions of LV-miR-133b-3p or LV-miR-143-3p resulting in a sustained reversal of pain when co-injected 3 days following nerve injury.
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Cholinergic stimulation coupled with visual conditioning enhances the visual acuity and cortical responses in the primary visual cortex. To determine which cholinergic receptors are involved in these processes, qRT-PCR was used. Two modes of cholinergic enhancement were tested: a phasic increase of acetylcholine release by an electrical stimulation of the basal forebrain cholinergic nucleus projecting to the visual cortex, or a tonic pharmacological potentiation of the cholinergic transmission by the acetylcholine esterase inhibitor, donepezil. ⋯ A Kruskal-Wallis test showed a modulation of the expression in the visual cortex of m2, m3, m4, m5, α7, β4, NMDA and GAD65, but only β4 within the basal forebrain and none of these mRNA within the somatosensory cortex. The two modes of cholinergic enhancement induced different effects on mRNA expression, related to the number of visual conditioning sessions and receptor specificity. This study suggests that the combination of cholinergic enhancement and visual conditioning is specific to the visual cortex and varies between phasic or tonic manipulation of acetylcholine levels.
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Comparative Study
Masking Differentially Affects Envelope-following Responses in Young and Aged Animals.
Age-related hearing decline typically includes threshold shifts as well as reduced wave I auditory brainstem response (ABR) amplitudes due to cochlear synaptopathy/neuropathy, which may compromise precise coding of suprathreshold speech envelopes. This is supported by findings with older listeners, who have difficulties in envelope and speech processing, especially in noise. However, separating the effects of threshold elevation, synaptopathy, and degradation by noise on physiological representations may be difficult. ⋯ High-pass noise may affect EFR amplitudes in young animals more than aged by reducing the contributions of high-frequency-sensitive inputs. EFRs to SAM tones in modulated noise (NAM) suggest that neurons of young animals can synchronize to NAM at lower sound levels and maintain dual AM representations better than older animals. The overall results show that EFR amplitudes are strongly influenced by aging and the presence of a competing sound that likely reduces or shifts the pool of responsive neurons.