Neuroscience
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Low doses (0.2-0.8 microM) of capsaicin were used to achieve selective excitation of C-fibres and the consequent synaptic activation of dorsal horn neurons (laminae I-VI) in the spinal cord of the 12-20-day-old mouse, maintained in vitro. Most dorsal horn cells were activated by application of capsaicin to dorsal root ganglia. The response consisted of a long-lasting membrane depolarization with increased regenerative (synaptic) activity in 79% of the cells, and in a further 7% only an increased synaptic activity was evoked. ⋯ This effect was paralleled with the loss of the prolonged (-)-2-amino-5-phosphonovaleric acid-sensitive phase of the excitatory postsynaptic potential evoked by the high-intensity electrical stimulation of dorsal roots. This observation suggested that activation of the N-methyl-D-aspartate receptors in the dorsal horn can be activated by small-calibre capsaicin-sensitive fibres. In summary, our data suggest that the selective activation of C-fibre afferents with capsaicin produces synaptic activity in the dorsal horn which has a strong excitatory amino acid component as well as a non-excitatory amino acid, possibly peptidergic, component.
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In anaesthetized rats, recordings were made from nociceptive dorsal horn neurons with convergent input from the skin and deep somatic tissues. The results of a previous study have shown that in these neurons the input from deep nociceptors is subjected to a much stronger tonic descending inhibition than is the input from cutaneous nociceptors. The aim of the present study was to find out whether at supraspinal levels opioidergic, adrenergic, or serotoninergic transmitters are involved in this quite specific inhibition of deep nociception. ⋯ In contrast, supraspinal adrenergic and serotoninergic mechanisms do not appear to contribute to the tonic inhibition. The data confirm and extend previous results which suggested that a particular portion of the descending antinociceptive system may act mainly on the input from deep nociceptors. Pharmacologically, this particular portion seems to be opioidergic in nature.
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Following a set of studies concerning the intrinsic electrophysiology of mammalian central neurons in relation to global brain function, we reach the following conclusions: (i) the main difference between wakefulness and paradoxical sleep lies in the weight given to sensory afferents in cognitive images; (ii) otherwise, wakefulness and paradoxical sleep are fundamentally equivalent brain states probably subserved by an intrinsic thalamo-cortical loop. From this assumption, we conclude that wakefulness is an intrinsic functional realm, modulated by sensory parameters. In support of this hypothesis, we review morphological studies of the thalamocortical system, which indicate that only a minor part of its connectivity is devoted to the transfer of direct sensory input. ⋯ These considerations lead us to challenge the traditional Jamesian view of brain function according to which consciousness is generated as an exclusive by-product of sensory input. Instead, we argue that consciousness is fundamentally a closed-loop property, in which the ability of cells to be intrinsically active plays a central role. We further discuss the importance of spatial and temporal mapping in the elaboration of cognitive and perceptual constructs.
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Recordings were made from neurons in subnucleus reticularis dorsalis of the rat. Two populations of neurons could be distinguished: those with total nociceptive convergence which were driven by activating A delta- and C-fibers from any part of the body and those with partial nociceptive convergence which were driven by activating A delta-fibers from any part of the body or C-fibers from some, mainly contralateral, regions. The effects on subnucleus reticularis dorsalis neurons of manual acupuncture, performed by a traditional Chinese acupuncturist at the "Renzhong", "Sousanli", "Changqiang", and "Zusanli" acupoints and at a non-acupoint next to "Zusanli", were studied. ⋯ No differences were found between the capacities to activate subnucleus reticularis dorsalis neurons of the "Zusanli" point and the adjacent non-acupoint, no matter whether these were stimulated ipsi- or contralaterally; this suggests a lack of topographical specificity in the activation of these neurons. Since subnucleus reticularis dorsalis neurons are activated exclusively or preferentially by noxious inputs, it is concluded that the signals elicited by manual acupuncture travel through pathways responsible for the transmission of nociceptive information. Since acupuncture, a manoeuvre which is known to elicit widespread extrasegmental antinociceptive effects, activates subnucleus reticularis dorsalis neurons which, anatomically, send dense projections to the dorsal horn at all levels of the spinal cord, we would suggest that this structure may be involved not only in signalling pain but also in modulating pain by means of spino-reticulo-spinal feed-back mechanisms.
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The effect of capsaicin on voltage-activated calcium currents was investigated in voltage-clamped somata of cultured adult rat dorsal root ganglion neurons. About half the neurons studied were sensitive to capsaicin, which induced an inward current at negative membrane potentials accompanied by an increase in membrane conductance. In the sensitive neurons capsaicin inhibited voltage-activated calcium current to an extent that depended on the size and duration of the capsaicin-induced inward current. ⋯ Substituting Ca with Co did not prevent the prolonged block of calcium channels. It is concluded that the inhibition of voltage-activated calcium currents by capsaicin is secondary to increased intracellular Ca levels due to calcium entry through capsaicin-activated cation-specific ion channels in the plasma membrane. Long-lasting inhibition of voltage-activated calcium channels may contribute to the mechanism of the analgesic and anti-inflammatory effects of capsaicin through inhibition of neurotransmitter release from central and peripheral terminals of primary afferent nociceptive neurons.