The Journal of neuroscience : the official journal of the Society for Neuroscience
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The neural mechanism responsible for migraine remains unclear. While an external trigger has been proposed to initiate a migraine, it has also been proposed that changes in brainstem function are critical for migraine headache initiation and maintenance. Although the idea of altered brainstem function has some indirect support, no study has directly measured brainstem pain modulation circuitry function in migraineurs particularly immediately before a migraine. ⋯ Contrary to our hypothesis, we found that pain sensitivity decreased immediately before a migraine, and this was coupled with increased sensitivity of the spinal trigeminal nucleus to noxious stimuli. We also found that resting connectivity within endogenous pain modulation circuitry alters across the migraine cycle. These changes may reflect enhanced and diminished neural tone states proposed to be critical for the generation of a migraine and underlie cyclic fluctuations in migraine brainstem sensitivity.
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Recent work has shown that, when countering external forces, the nervous system adjusts not only predictive (i.e., feedforward) control of reaching but also reflex (i.e., feedback) responses to mechanical perturbations. Here we show that altering the physical properties of the arm (i.e., intersegmental dynamics) causes the nervous system to adjust feedforward control and that this learning transfers to feedback responses even though the latter were never directly trained. Forty-five human participants (30 females) performed a single-joint elbow reaching task and countered mechanical perturbations that created pure elbow motion. ⋯ Our work suggests that feedforward and feedback control share an internal model of the arm's dynamics. SIGNIFICANCE STATEMENT Here we show that altering the physical properties of the arm causes people to learn new motor commands and that this learning transfers to their reflex responses to unexpected mechanical perturbations, even though the reflex responses were never directly trained. Our results suggest that feedforward motor commands and reflex responses share an internal model of the arm's dynamics.
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Mechanical allodynia, a widespread pain symptom that still lacks effective therapy, is associated with the activation of a dorsally directed polysynaptic circuit within the spinal dorsal horn (SDH) or medullary dorsal horn (MDH), whereby tactile inputs into deep SDH/MDH can gain access to superficial SDH/MDH, eliciting pain. Inner lamina II (IIi) interneurons expressing the γ isoform of protein kinase C (PKCγ+) are key elements for allodynia circuits, but how they operate is still unclear. Combining behavioral, ex vivo electrophysiological, and morphological approaches in an adult rat model of facial inflammatory pain (complete Freund's adjuvant, CFA), we show that the mechanical allodynia observed 1 h after CFA injection is associated with the following (1) sensitization (using ERK1/2 phosphorylation as a marker) and (2) reduced dendritic arborizations and enhanced spine density in exclusively PKCγ+ interneurons, but (3) depolarized resting membrane potential (RMP) in all lamina IIi PKCγ+/PKCγ- interneurons. ⋯ We discovered that facial inflammation-induced mechanical allodynia is associated with rapid and strong structural remodeling of specifically interneurons expressing the γ isoform of protein kinase C (PKCγ) within MDH inner lamina II. Moreover, we elucidated a 5-HT2A receptor to PKCγ/ERK1/2 pathway leading to the behavioral allodynia and correlated morphological changes in PKCγ interneurons. Therefore, descending 5-HT sensitize PKCγ interneurons, a putative "gate" in allodynia circuits, via 5-HT2A receptor-induced structural reorganization.