Journal of neurophysiology
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Pain has a strong emotional dimension, and the amygdala plays a key role in emotionality. The processing of nociceptive mechanical and thermal information was studied in individual neurons of the central nucleus of the amygdala, the target of the spino-parabrachio-amygdaloid pain pathway and a major output nucleus of the amygdala. This study is the first to characterize nociceptive amygdala neurons with input from deep tissue, particularly the knee joint. ⋯ Fifteen neurons had no receptive field in the knee but responded to noxious stimulation of other body areas; 27 nonresponsive neurons were not activated by natural somesthetic stimulation. Our data suggest that excitation is the predominant effect of brief painful stimulation of somatic tissue on the population of central amygdala neurons with knee joint input. Their large symmetrical receptive fields and sigmoid rather than monotonically increasing linear stimulus-response functions suggest a role of nociceptive central amygdala neurons in other than sensory-discriminative aspects of pain.
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GABAergic interneurons in the hippocampus express high levels of alpha7 nicotinic acetylcholine receptors, but because of the diverse roles played by hippocampal interneurons, the impact of activation of these receptors on hippocampal output neurons (i.e., CA1 pyramidal cells) is unclear. Activation of hippocampal interneurons could directly inhibit pyramidal neuron activity but could also produce inhibition of other GABAergic cells leading to disinhibition of pyramidal cells. To characterize the inhibitory circuits activated by these receptors, exogenous acetylcholine was applied directly to CA1 interneurons in hippocampal slices, and the resulting postsynaptic responses were recorded from pyramidal neurons or interneurons. ⋯ In 11 interneuron/interneuron cell pairs, one presynaptic neuron was observed that produced strong inhibitory currents in several nearby interneurons, suggesting that disinhibition of pyramidal neurons may also occur. All three types of inhibitory responses (somatic-pyramidal, dendritic-pyramidal, and interneuronal) were blocked by the alpha7 receptor-selective antagonist methyllycaconitine. These data suggest activation of these functionally distinct circuits by alpha7 receptors results in significant inhibition of both hippocampal pyramidal neurons as well as interneurons.
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The effects of inferior alveolar nerve (IAN) transection on escape behavior and MDH neuronal activity to noxious and nonnoxious stimulation of the face were precisely analyzed. Relative thresholds for escape from mechanical stimulation applied to the whisker pad area ipsilateral to the transection were significantly lower than that for the contralateral and sham-operated whisker pad until 28 days after the transection, then returned to the preoperative level at 40 days after transection. A total of 540 neurons were recorded from the medullary dorsal horn (MDH) of the nontreated naive rats [low-threshold mechanoreceptive (LTM), 27; wide dynamic range (WDR), 31; nociceptive specific (NS), 11] and sham-operated rats with skin incision (LTM, 34; WDR, 30; NS, 23) and from the ipsilateral (LTM, 82; WDR, 82; NS, 31) and contralateral MDH relative to the IAN transection (LTM, 77; WDR, 82; NS, 33). ⋯ We could not observe any modulation of thermal responses of WDR and NS neurons following IAN transection. Also, no MDH neurons were significantly affected in the rats with sham operations. The present findings suggest that the increment of neuronal activity of WDR neurons in the MDH following IAN transection may play an important role in the development of the mechano-allodynia induced in the area adjacent to the area innervated by the injured nerve.
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Bradykinin (BK), which has potent algesic and sensitizing effect on nociceptors, is of current interest in understanding the mechanisms of chronic pain. BK response is mediated by B2 receptor in normal conditions; however, findings that B1 receptor blockade alleviated hyperalgesia in inflammation have been highlighting the role of B1 receptor in pathological conditions. It has not yet been clear whether nociceptor activities are modified by B1 receptor agonists or antagonists during inflammation. ⋯ A B2 receptor antagonist (D-Arg-[Hyp3, Thi5,8,D-phe7]-BK) completely eliminated BK responses in inflamed rats, while B1 receptor antagonists (B 9958 and Des-Arg9-[Leu8]-BK) had no effect. Selective B1 receptor agonist (Des-Arg10-Kallidin) excited 46% (n = 13) of inflamed C-fibers at 10(-5) M concentration, which is 1,000 times higher than that of BK needed to excite the same percentage of inflamed C-fibers. We conclude that in chronically inflamed tissue, sensitivity of C-fiber nociceptors to BK, which is B2 receptor mediated, is strongly increased and that B1 receptor may not be important to a persistent inflammatory state, at least at the primary afferent level.
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Comparative Study Clinical Trial
Consonance and dissonance of musical chords: neural correlates in auditory cortex of monkeys and humans.
Some musical chords sound pleasant, or consonant, while others sound unpleasant, or dissonant. Helmholtz's psychoacoustic theory of consonance and dissonance attributes the perception of dissonance to the sensation of "beats" and "roughness" caused by interactions in the auditory periphery between adjacent partials of complex tones comprising a musical chord. Conversely, consonance is characterized by the relative absence of beats and roughness. ⋯ AEPs recorded in Heschl's gyrus display strikingly similar oscillatory patterns to those observed in monkey A1, with dissonant chords eliciting greater phase-locked activity than consonant chords. In contrast to recordings in Heschl's gyrus, AEPs recorded in the planum temporale do not display significant phase-locked activity, suggesting functional differentiation of auditory cortical regions in humans. These findings support the relevance of synchronous phase-locked neural ensemble activity in A1 for the physiological representation of sensory dissonance in humans and highlight the merits of complementary monkey/human studies in the investigation of neural substrates underlying auditory perception.