Journal of neurophysiology
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Corneal nociceptors terminate at the trigeminal subnucleus interpolaris/caudalis (Vi/Vc) transition and subnucleus caudalis/upper cervical spinal cord (Vc/C1) junction regions of the lower brain stem. The aims of this study were to determine if local GABAA receptor activation modifies corneal input to second-order neurons at these regions and if GABAA receptor activation in one region affects corneal input to the other region. In barbiturate-anesthetized male rats, corneal nociceptors were excited by pulses of CO2 gas, and GABAA receptors were activated by microinjections of the selective agonist muscimol. ⋯ To test for descending intersubnuclear communication, muscimol was injected remotely into the rostral Vi/Vc transition and enhanced the evoked activity of all corneal units tested at the caudal Vc/C1 junction. These results suggest that GABAA receptor mechanisms play a significant role in corneal nociceptive processing by second-order trigeminal brain stem neurons. GABAA receptor mechanisms act locally at both the Vi/Vc transition and Vc/C1 junction regions to inhibit corneal input and act through polysynaptic pathways to modify corneal input at multiple levels of the trigeminal brain stem complex.
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Peripheral N-methyl-d-aspartate (NMDA) receptors are found in deep tissues and may play a role in deep tissue pain. Injection of the endogenous NMDA receptor agonist glutamate into the masseter muscle excites deep craniofacial afferent fibers in rats and evokes pain in human subjects. It is not clear whether peripheral NMDA receptors play a role in these effects of glutamate. ⋯ In human experiments, it was found that 10 mM ketamine decreased glutamate-evoked muscle pain but had no effect on hypertonic saline-evoked muscle pain. These results indicate that injection of glutamate into the masseter muscle evokes afferent discharges in rats and muscle pain in humans in part through activation of peripheral NMDA receptors. It is conceivable that activation of peripheral NMDA receptors may contribute to masticatory muscle pain and that peripherally acting NMDA receptor antagonists could prove to be effective analgesics for this type of pain.
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Comparative Study
mGluR1, but not mGluR5, mediates depolarization of spinal cord neurons by blocking a leak current.
The modulation of neuronal excitability by group I metabotropic glutamate receptors (mGluRs) was studied in isolated lamprey spinal cord. At resting potential, application of the group I mGluR agonist (R,S)-3,5-dihydroxyphenylglycine (DHPG) slightly depolarized the cells. However, at depolarized membrane potentials, this agonist induced repetitive firing. ⋯ The DHPG-induced blockage of the leak current required phospholipase C (PLC)-activation and release of Ca2+ from internal stores as the effect of DHPG was suppressed by the PLC-blocker U-73122 and after depletion of intracellular Ca2+ pools by thapsigargin. Our results thus show that mGluR1 activation depolarizes spinal neurons by inhibiting a leak current. This will boost membrane depolarization and result in an increase in the excitability of spinal cord neurons, which could contribute to the modulation of the activity of the spinal locomotor network.
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We examined the rostro-caudal dendritic spread of striatally projecting dopaminergic neurons of the Substantia Nigra pars compacta (SNc) and investigated the presence of dye-coupling after labeling these cells with a mixture of lucifer yellow (LY) and neurobiotin (NB) or with LY alone. Whole cell recordings were made from horizontal brain slices (400 microm) obtained from P5-P20 rats. SNc neurons retrogradely labeled with Fluoro-Gold and located in the region containing tyrosine hydroxylase-immunoreactive cells displayed Ih current and other properties characteristic of SNc neurons. ⋯ In addition, none of the tested SNc cells (n = 12) showed expression of connexin 36 (the "neuronal" connexin) when tested with single-cell RT-PCR. In conclusion, this study revealed extensive rostro-caudal dendritic projections of SNc neurons. Under our in vitro conditions, no evidence was found for dye-coupling among these neurons.
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Elevating glucocorticoids in the amygdala produces colorectal hypersensitivity through activation of lumbosacral spinal neurons. The aim of this study was to determine if descending modulation from the amygdala affects spinal processing of input from urinary bladder afferents. Fischer-344 rats received cholesterol (inactive control)-, corticosterone-, or aldosterone-containing micropellets placed stereotaxically on the dorsal margin of the left and right amygdala (n = 10 for each group). ⋯ Neurons with low thresholds for excitatory responses to UBD were seen more frequently in aldosterone-implanted rats than in corticosterone or cholesterol treated rats (74 vs. 44% and 39%, P < 0.05). No difference in somatic field properties of spinal neurons responsive or nonresponsive to UBD was found among the three groups. These findings suggest that both mineralocorticoid- and glucocorticoid-mediated mechanisms in the amygdala are involved in descending modulation to lumbosacral spinal neurons receiving inputs from the urinary bladder; and this mechanism may play a role in the activation and maintenance of primary central sensitization to noxious visceral stimuli.