Neuroscience
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The opioid receptor-like 1 (ORL1) receptor shares a high degree of sequence homology with the classical mu-, delta- and kappa-opioid receptors and a functional mutual opposition between these receptors has been suggested. To further address this possible interaction we have used mu-, delta- and kappa-opioid receptor knockout mice to determine autoradiographically if there are any changes in the number or distribution of the ORL1 receptor, labelled with [(3)H]nociceptin, in the brains of mice deficient in each of the opioid receptors. An up-regulation of ORL1 expression was observed across all brain regions in delta-knockouts with cortical regions typically showing a 15-30% increase in binding that was most marked in heterozygous mice. ⋯ No significant alterations in ORL1 receptor expression were observed across brain regions in mu-receptor knockout mice and there were no qualitative differences in ORL1 receptor expression in any groups. These data suggest there are interactions between the ORL1 system and the classical opioid receptors and that the interactions are receptor-specific. The greater differences observed in heterozygous mice suggest that these interactions might be most relevant when there is only partial loss of receptor function.
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Vagal afferents ascending from the gastrointestinal tract synapse on neurons in the nucleus of the solitary tract. Although these neurons constitute a significant proportion of solitary tract cells their firing behaviour and synaptic properties are not documented. Since gastrointestinal tract afferent termination sites overlap with regions mediating cardiorespiratory reflexes the possibility of convergence with afferents mediating cardiovascular and respiratory reflexes was proposed. ⋯ We conclude that solitary tract neurons receiving signals from the sub-diaphragmatic vagus nerves (most likely from gastrointestinal tract structures) appear to be a distinct pool of neurons. There was a heterogeneity in terms of both their ongoing activity and projection targets but despite this, there were three consistent properties. First, sub-diaphragmatic vagus nerve evoked predominantly excitatory synaptic responses in solitary tract neurons; second, neurons exhibited lasting paired pulse depression following activation of sub-diaphragmatic vagus nerves; and third, sub-diaphragmatic vagus nerve-driven solitary tract neurons were
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Brain-derived neurotrophic factor, the most abundant of the neurotrophins in the brain, enhances the growth and maintenance of several neuronal systems, serves as a neurotransmitter modulator, and participates in use-dependent plasticity mechanisms such as long-term potentiation and learning. In recent years, evidence has been gathering that brain-derived neurotrophic factor may have an important role in the neuropathology and treatment of depression. It has recently been reported that chronic (at least two weeks) antidepressant treatment leads to an up-regulation of brain-derived neurotrophic factor messenger RNA levels in the hippocampus, an important brain area for behavioral regulation, as well as learning and memory. ⋯ In this report, we have tested the hypothesis that the combination of these two interventions, general physical activity and antidepressant treatment, leads to increased levels of specific promoter-derived transcripts of brain-derived neurotrophic factor messenger RNA in a manner that appears to be both additive and accelerated. Our results suggest that these two very different interventions may possibly converge at the cellular level. The induction of brain-derived neurotrophic factor expression by activity/pharmacological treatment combinations could represent an important intervention for further study, to potentially improve depression treatment and management.
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The aim of this investigation was to determine whether murine models of inflammatory, neuropathic and cancer pain are each characterized by a unique set of neurochemical changes in the spinal cord and sensory neurons. All models were generated in C3H/HeJ mice and hyperalgesia and allodynia behaviorally characterized. A variety of neurochemical markers that have been implicated in the generation and maintenance of chronic pain were then examined in spinal cord and primary afferent neurons. ⋯ However, in this cancer-pain model, changes including massive astrocyte hypertrophy without neuronal loss, increase in the neuronal expression of c-Fos, and increase in the number of dynorphin-immunoreactive neurons were observed in the spinal cord, ipsilateral to the limb with cancer. These results indicate that a unique set of neurochemical changes occur with inflammatory, neuropathic and cancer pain in C3H/HeJ mice and further suggest that cancer induces a unique persistent pain state. Determining whether these neurochemical changes are involved in the generation and maintenance of each type of persistent pain may provide insight into the mechanisms that underlie each of these pain states.
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Single unmyelinated axons in the superficial branch of the peroneal nerve of human subjects were recorded (microneurography) and the response patterns during tonic pressure stimulation (14N at 30 mm(2); 120 s) were assessed using the previously described "marking technique". It was found that tonic pressure stimuli induced augmenting pain responses which were matched by the discharges of initially mechano-insensitive ("silent") C-units, whereas mechano- and heat-responsive "polymodal" C-nociceptors showed a response pattern incompatible with the stimulus-induced perceptions, namely strong initial excitation, followed by adaptation. Eighteen mechano- and heat-responsive "polymodal" C-fibers and 11 mechano-insensitive units were studied. ⋯ A second, identical pressure stimulus induced a stronger response in mechano-insensitive and a weaker response in mechano-responsive units. The stronger response, indicating sensitization, matched the more intense pain perception during the second pressure stimulus. It is concluded that mechano-insensitive C-nociceptors encode pressure-induced pain in human hairy skin and that they play an important role in static mechanical hyperalgesia.