Neuroscience
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Excessive activation of NMDA receptor (NMDAR) signaling within the spinal dorsal horn contributes to central sensitization and the induction and maintenance of pathological pain states. However, direct antagonism of NMDARs produces undesirable side effects which limit their clinical use. NMDAR activation produces central sensitization, in part, by initiating a signaling cascade that activates the enzyme neuronal nitric oxide synthase (nNOS) and generates the signaling molecule nitric oxide. ⋯ ZL006 but not ZL007 suppressed paclitaxel-induced mechanical and cold allodynia in a model of chemotherapy-induced neuropathic pain. Co-immunoprecipitation experiments revealed the presence of the PSD95-nNOS complex in lumbar spinal cord of paclitaxel-treated rats, although ZL006 did not reliably disrupt the complex in all subjects. The present findings validate use of putative small molecule PSD95-nNOS protein-protein interaction inhibitors as novel analgesics and demonstrate, for the first time, that these inhibitors suppress inflammation-evoked neuronal activation at the level of the spinal dorsal horn.
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Pain is processed in a large neural network that partially overlaps structures involved in emotion processing. Despite the fact that pain and emotion are known to share neural regions and interact in numerous clinical conditions, relatively little is known about the interaction of pain and emotion at the neural level. This study on healthy adults aimed to investigate the interaction between negative and positive emotional stimuli and experimental pain in an essential pain processing network. ⋯ The interaction of positive emotion and pain stimuli led to bilateral activation of the SII and left insula. These findings reveal interaction in parts of the pain processing network during simultaneous emotion and physical pain. We demonstrated a valence-independent interaction of emotion and pain in SII.
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Human standing balance control requires the integration of sensory feedback to produce anticipatory, stabilizing ankle torques. However, the ability of human triceps surae muscle spindles to provide reliable sensory feedback regarding the small, slow ankle movements that occur during upright standing has recently come under question. We performed microneurography to directly record axon potentials from single muscle spindle afferents in the human triceps surae during servo-controlled movement of the ankle joint. ⋯ Concatenating within muscles, coherence was significantly greater for soleus spindles at all stimulus frequencies. Voluntary contraction of the parent muscle reduced spindle sensitivity, but only significantly near the mean power frequency of the stimulus (∼0.3Hz). In conclusion, these results provide direct evidence that triceps surae muscle spindles are potentially capable of providing important sensory feedback for the control of human standing balance.
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Spontaneous epileptiform activity has previously been observed in lateral amygdala (LA) slices derived from patients with intractable-temporal lobe epilepsy. The present study aimed to characterize intranuclear LA synaptic connectivity and to test the hypothesis that differences in the spread of flow of neuronal activity may relate to spontaneous epileptiform activity occurrence. Electrical activity was evoked through electrical microstimulation in acute human brain slices containing the LA, signals were recorded as local field potentials combined with fast optical imaging of voltage-sensitive dye fluorescence. ⋯ No differences in spread of evoked activity were observed between spontaneously and non-spontaneously active LA slices, i.e. basic properties of evoked synaptic responses were similar in the two functional types of LA slices, including input-output relationship, and paired-pulse depression. These results indicate a directed propagation of synaptic signals within the human LA in spontaneously active epileptic slices. We suggest that the lack of differences in local and in systemic information processing has to be found in confined epileptiform circuits within the amygdala likely involving well-known "epileptic neurons".