Neuroscience
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c-Fos has been used as a marker for activity in the spinal cord following noxious somatic or visceral stimulation. Although the viscera receive dual afferent innervation, distention of hollow organs (i.e. esophagus, stomach, descending colon and rectum) induces significantly more c-Fos in second order neurons in the nucleus of the solitary tract and lumbosacral spinal cord, which receive parasympathetic afferent input (vagus, pelvic nerves), than the thoracolumbar spinal cord, which receives sympathetic afferent input (splanchnic nerves). The purpose of this study was to determine the contribution of sympathetic and parasympathetic afferent input to c-Fos expression in the nucleus of the solitary tract and spinal cord, and the influence of supraspinal pathways on Fos induction in the thoracolumbar spinal cord. ⋯ The induction of c-Fos in the nucleus of the solitary tract is significantly greater than in the viscerotopic segments of the spinal cord, which is partially under tonic descending inhibition, but is not subject to modulation by vagal gastric afferents. Distention pressures produced by noxious gastric distention are much greater than those produced during feeding, suggesting that c-Fos induction in the nucleus of the solitary tract to noxious distention is not associated with physiological mechanisms of feeding and satiety. The large vagal nerve-mediated induction of c-Fos in the nucleus of the solitary tract following gastric distension suggests that parasympathetic afferents contribute to the processing of noxious visceral stimuli, perhaps by contributing to the affective-emotional component of visceral pain.
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The effects of a recently synthesized benzoyl-piperidine drug that enhances currents mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-type glutamate receptors were tested on monosynaptic and polysynaptic responses in hippocampal slices of the rat. Stimulation of perforant path inputs to the dentate gyrus evoked extracellular responses in field CA1 that had latencies and laminar profiles indicating that they were relayed through the trisynaptic intrahippocampal circuit. Under control conditions, trisynaptic field excitatory postsynaptic potentials did not show larger paired-pulse facilitation than monosynaptic responses and failed to exhibit frequency facilitation. ⋯ The AMPA receptor modulator did not change the frequency characteristics of monosynaptic potentials and had only a modest influence on those of the trisynaptic response. The effect of benzoyl-piperidine-12 on trisynaptic responses was significantly greater when GABAergic inhibition was partially blocked with picrotoxin; the GABA blocker did not alter the effects of benzoyl-piperidine-12 on monosynaptic responses. These results indicate that centrally active AMPA receptor modulators are likely to have a greater influence on brain operations involving long chains of connections than on those mediated by simple reflex-like circuits, and will vary markedly in their effects depending upon the excitability of local interneurons.
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Electrical excitation of nociceptive afferents in an extremity has been demonstrated to increase skin blood flow in the contralateral extremity. Hence, one would expect that loose sciatic nerve ligation, which induces an experimental painful peripheral neuropathy, may also provoke a vasodilator response in the contralateral hindpaw. On the non-ligated side, such a response may involve inhibited skin vasoconstrictor activity as well as neurogenically mediated active vasodilation. ⋯ Besides, blockade of sensory but not of non-sensory nerve fibers on the non-ligated side attenuated the vasodilator response in this paw. The data presented here indicate that loose ligation of the rat sciatic nerve induces a vasodilator response in the contralateral hindpaw. On the non-ligated side, this vasodilator response may involve inhibition of skin vasoconstrictor activity, as well as antidromically acting sensory nerve fibers.
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Cortical structures such as the hippocampus and cerebral cortex are considered to be particularly susceptible to seizure and epileptiform electrical activity and, as such, are the focus of intense investigation relative to hyperexcitability. To determine whether parallel glutamate-mediated hyperexcitability and seizure-like activity in the rat can be generated by neurons irrespective of their origin within the CNS, we maintained cells from the spinal cord,hippocampus, olfactory bulb, striatum, hypothalamus, and cortex in the long-term presence of glutamate receptor antagonists 2-amino-5-phosphonovalerate and 6-cyano-7-nitroquinoxaline-2-3-dione. After removal of chronic (three to 11 weeks) glutamate receptor block, whole-cell patch-clamp recordings from current-clamped neurons (n = 94) revealed an immediate increase in large excitatory postsynaptic potentials and a depolarization of 20-35 mV that was often sustained for recording periods lasting 5 min (54% of 66 neurons from all six areas). ⋯ Sufficient amounts of glutamate can be released from axon terminals from all areas to cause cell hippocampal and cortical neurons, but also by neurons from any of the brain regions tested after chronic deprivation of glutamate receptor stimulation during development. This hyperexcitability is mediated by glutamatergic mechanisms independent of the specific excitatory connections existing in vivo. The epileptiform activity of neurons from one region is indistinguishable from that of another in culture, underlining the importance of synaptic connections in vivo that define the responses characteristic of neurons from different brain regions.
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The rostral ventromedial medulla is a critical relay for midbrain regions, including the periaqueductal gray and nucleus cuneiformis, that control nociception at the spinal cord. Opioid-containing neurons and terminals are concentrated in both the periaqueductal gray and the rostral ventromedial medulla in the rat. However, the function of endogenous opioid peptides within the medulla in pain modulation is unclear. ⋯ The firing of off-cells (cells that pause in firing just prior to tail-flick) in the medulla was increased by bicuculline applied in the periaqueductal gray and was not affected by naloxone. The present results suggest that when activation of neurons in the periaqueductal gray produces antinociception, endogenous opioid peptides are released in the rostral ventromedial medulla and selectively inhibit on-cells, which presumably have a facilitating action on spinal nociceptive transmission. This action is proposed to be critical for the behavioral antinociception induced by bicuculline or morphine in the periaqueductal gray.