Neuroscience
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Sympathetic cholinergic postganglionic neurons are present in many sympathetic ganglia. Three classes of sympathetic cholinergic neuron have been reported in mammals; sudomotor neurons, vasodilator neurons and neurons innervating the periosteum. We have examined thoracic sympathetic ganglia in rats to determine if any other classes of cholinergic neurons exist. ⋯ Cholinergic neurons innervating the periosteum were usually surrounded by terminals immunoreactive for CGRP. We conclude that if any undiscovered populations of cholinergic neurons exist in the rat thoracic sympathetic chain, then they are indistinguishable in size, neurochemistry and inputs from sudomotor or cholinergic neurons innervating the periosteum. It may be that the latter two populations account for all cholinergic neurons in the rat thoracic sympathetic chain ganglia.
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Corticotropin releasing factor, acting at hypothalamic corticotropin releasing factor receptors, contributes to the neural signaling pathways mediating stress-related responses, as well as those involved in maintaining energy balance homeostasis. Sympathetically-regulated lipid metabolism and heat production in brown adipose tissue contributes to the non-shivering thermogenic component of stress-evoked hyperthermia and to energy expenditure aspects of body weight regulation. To identify potential central pathways through which hypothalamic corticotropin releasing factor influences brown adipose tissue thermogenesis, corticotropin releasing factor was microinjected into the lateral ventricle (i.c.v.) or into hypothalamic sites while recording sympathetic outflow to brown adipose tissue, brown adipose tissue temperature, expired CO2, heart rate and arterial pressure in urethane/chloralose-anesthetized, artificially-ventilated rats. ⋯ These sympathetic responses to i.c.v. corticotropin releasing factor were eliminated by inhibition of neuronal activity in the dorsomedial hypothalamus or in the raphe pallidus, a putative site of sympathetic premotor neurons for brown adipose tissue, and were markedly reduced by microinjection of ionotropic glutamate receptor antagonists into the dorsomedial hypothalamus. The increases in brown adipose tissue sympathetic outflow, brown adipose tissue temperature and heart rate elicited from corticotropin releasing factor into the preoptic area were reversed by inhibition of neuronal discharge in dorsomedial hypothalamus. These data indicate that corticotropin releasing factor release within the preoptic area activates a sympathoexcitatory pathway to brown adipose tissue and to the heart, perhaps similar to that activated by increased prostaglandin production in the preoptic area, that includes neurons in the dorsomedial hypothalamus and in the raphe pallidus.
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Comparative Study Clinical Trial
Cortical changes to experimental sensitization of the human esophagus.
Topographical organization in the neocortex shows experience-dependent plasticity. We hypothesized that experimental sensitization of the esophagus results in changes of the topographical distribution of the evoked potentials and the corresponding dipole source activities to painful stimulation. An endoscopic method was used to deliver 35 electrical stimuli at the pain threshold to a fixed area of the mucosa in 10 healthy volunteer men and women. ⋯ The source analysis showed consistent dipolar activity in the bilateral opercular-insular cortex before and after acid perfusion. For the anterior cingulate dipole there was a reduction in latency (P=0.03) and a posterior shift (P=0.0002) following acid perfusion. The findings indicate that short-term sensitization of the esophagus results in central neuroplastic changes involving the cingulate gyrus, which also showed pathological activation in functional diseases of the gut, thus reflecting the importance of this region in visceral pain and hyperalgesia.
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Comparative Study
Deletion of the neuropeptide Y Y1 receptor affects pain sensitivity, neuropeptide transport and expression, and dorsal root ganglion neuron numbers.
Neuropeptide Y has been implicated in pain modulation and is substantially up-regulated in dorsal root ganglia after peripheral nerve injury. To identify the role of neuropeptide Y after axotomy, we investigated the behavioral and neurochemical phenotype of neuropeptide Y Y1 receptor knockout mice with focus on dorsal root ganglion neurons and spinal cord. Using a specific antibody Y1 receptor immunoreactivity was found in dorsal root ganglia and in dorsal horn neurons of wild-type, but not knockout mice. ⋯ However, the transcript levels for calcitonin gene-related peptide and substance P were significantly higher in knockout than in wild-type dorsal root ganglia ipsilateral to the axotomy, while more calcitonin gene-related peptide- and substance P-like immunoreactivity accumulated proximal and distal to a crush of the sciatic nerve. These results indicate that the deletion of the Y1 receptor causes increased release and compensatory increased synthesis of calcitonin gene-related peptide and substance P in dorsal root ganglion neurons. Together, these findings suggest that, after peripheral nerve injury, neuropeptide Y, via its Y1 receptor receptor, plays a key role in cell survival as well as in transport and synthesis of the excitatory dorsal horn messengers calcitonin gene-related peptide and substance P and thus may contribute to pain hypersensitivity.
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Comparative Study
Involvement of brain protein kinase C in nitrous oxide-induced antinociception in mice.
Exposure of mice to the anesthetic gas nitrous oxide (N(2)O) produces a marked antinociceptive effect. Protein kinase C is a key regulatory enzyme that may be targeted by general anesthetics. However, a relationship between N(2)O-induced antinociception and protein kinase C has yet to be established. ⋯ Regarding activation of protein kinase C, regular exposure to 70% N(2)O did not increase protein kinase C within the membrane fraction of brain tissue, as determined by immunoblot analysis, but long-term exposure to 70% N(2)O did. The i.c.v. pretreatment with calphostin C and phorbol 12,13-dibutyrate prevented the increase in protein kinase C observed with long-term exposure to 70% N(2)O. These results suggest that brain protein kinase C negatively regulates the antinociceptive effect of N(2)O, and that activation of brain protein kinase C is related to the development of acute tolerance to N(2)O-induced antinociception in mice.