Neuroscience
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Cyclooxygenase-2 (COX-2) after induction peripherally, and within the CNS, plays an important role in producing inflammatory pain. However, its role in neuropathic pain models is controversial. Recently a robust and persistent model of partial nerve injury pain, the spared nerve injury (SNI) model, has been developed. ⋯ Furthermore, rofecoxib treatment (1 and 3.2 mg/kg for 5 and 3 days respectively starting on the day of surgery) failed to modify the development of allodynia and hyperalgesia in the SNI model. However, rofecoxib significantly reduced inflammatory hypersensitivity evoked by injection of complete Freund's adjuvant into one hindpaw, indicating that the doses used were pharmacologically active. The pain hypersensitivity produced by the SNI model is not COX-2-dependent.
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The cellular localization of the vesicular glutamate transporter 1, VGLUT1, was studied in the rat cerebral cortex with immunocytochemical techniques. VGLUT1 immunoreactivity (ir) was localized to punctate structures dispersed in the neuropil of all cortical layers as well as around the profile of somata and proximal dendritic segments of virtually all pyramidal neurons. ⋯ Perisomatic VGLUT1-positive terminals never formed synapses with the pyramidal cell bodies to which they were in apposition, but formed asymmetric synapses with adjacent neuropilar dendritic elements. The high probability of a close spatial relationship between glutamatergic and GABAergic terminals in perisomatic regions suggests that spilled-out glutamate may act on inhibitory axon terminals innervating the soma of cortical pyramidal neurons.
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Although there has been growing interest in the neuroanatomical and physiological mechanisms underlying aggressive behavior, little work has focused on possible mechanisms controlling natural plasticity in aggression. In the current study, we used naturally occurring changes in aggression level displayed by female Peromyscus californicus across the estrous cycle and parallel changes in c-fos expression to examine possible brain regions involved in mediating this plasticity. We found that c-fos expression was increased in females exposed to a conspecific female intruder compared with control females in numerous brain regions thought to be involved in the control of aggression. ⋯ Conversely, c-fos increased in the medial amygdala (MeA) across all stages of estrus compared with controls, suggesting the MeA is not involved in mediating changes in individual levels of aggression. Moreover, we found correlations between several measures of aggression and c-fos expression in the BNST and LSv but not the MeA, again suggesting a role in mediating aggression plasticity for the former two but not the latter brain region. We further hypothesize that the BNST and the LSv may be involved more generally in mediating natural changes in aggression, such as increases often observed after individuals win aggressive interactions against conspecifics.
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Comparative Study
Mouse strains that lack spinal dynorphin upregulation after peripheral nerve injury do not develop neuropathic pain.
Several experimental models of peripheral neuropathy show that a significant upregulation of spinal dynorphin A and its precursor peptide, prodynorphin, is a common consequence of nerve injury. A genetically modified mouse strain lacking prodynorphin does not exhibit sustained neuropathic pain after nerve injury, supporting a pronociceptive role of elevated levels of spinal dynorphin. A null mutation of the gamma isoform of protein kinase C (PKCgamma KO [knockout]), as well as an inbred mouse strain, 129S6, also does not manifest behavioral signs of neuropathic pain following peripheral nerve injury. ⋯ However, the PKCgamma KO mice and the 129S6 mice (which express PKCgamma) did not show abnormal pain after SNL; neither strain showed elevated levels of spinal dynorphin. The multiple phenotypic deficits in PKCgamma KO mice confound the interpretation of the proposed role of PKCgamma-expressing spinal neurons in neuropathic pain states. Additionally, the data show that the regulation of spinal dynorphin expression is a common critical feature of expression of neuropathic pain.
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In the lamprey, spinal locomotor activity can be initiated by pharmacological microstimulation in several brain areas: rostrolateral rhombencephalon (RLR); dorsolateral mesencephalon (DLM); ventromedial diencephalon (VMD); and reticular nuclei. During DLM- or VMD-initiated locomotor activity in in vitro brain/spinal cord preparations, application of a solution that focally depressed neuronal activity in reticular nuclei often attenuated or abolished the locomotor rhythm. Electrical microstimulation in the DLM or VMD elicited synaptic responses in reticulospinal (RS) neurons, and close temporal stimulation in both areas evoked responses that summated and could elicit action potentials when neither input alone was sufficient. ⋯ These new results suggest that neurons in the RLR project rostrally to locomotor areas in the DLM and VMD. These latter areas then appear to project caudally to RS neurons, which probably integrate the synaptic inputs from both areas and activate the spinal locomotor networks. These pathways are likely to be important components of the brain neural networks for the initiation of locomotion and have parallels to locomotor command systems in higher vertebrates.