Journal of neurophysiology
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Fentanyl, a mu-opioid receptor agonist, produces analgesia while leaving vibrotactile sensation intact. We used positron emission tomography (PET) to study the mechanisms mediating this specific effect in healthy, right-handed human males (ages 18-28 yr). Subjects received either painful cold (n = 11) or painless vibratory (n = 9) stimulation before and after the intravenous injection of fentanyl (1.5 microgram/kg) or placebo (saline). ⋯ In addition, fentanyl, compared with placebo, produces a unique activation of the mid-anterior cingulate cortex during fentanyl analgesia, suggesting that this region of the cingulate cortex participates actively in mediating opioid analgesia. The results are consistent with a selective, fentanyl-mediated suppression of nociceptive spinothalamic transmission to the forebrain. This effect could be implemented directly at the spinal level, indirectly through cingulate corticofugal pathways, or by a combination of both mechanisms.
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Primary sensory neurons with myelinated axons were examined in vitro in excised whole lumbar dorsal root ganglia (DRGs) taken from adult rats up to 9 days after tight ligation and transection of the L(5) spinal nerve (Chung model of neuropathic pain). Properties of subthreshold membrane potential oscillations, and of repetitive spike discharge, were examined. About 5% of the DRG neurons sampled in control DRGs exhibited high-frequency, subthreshold sinusoidal oscillations in their membrane potential at rest (V(r)), and an additional 4.4% developed such oscillations on depolarization. ⋯ Tactile allodynia following spinal nerve injury is thought to result from central amplification ("central sensitization") of afferent signals entering the spinal cord from residual intact afferents. The central sensitization, in turn, is thought to be triggered and maintained in the Chung model by ectopic firing originating in the axotomized afferent neurons. Axotomy by spinal nerve injury enhances subthreshold membrane potential oscillations in DRG neurons, augments ectopic discharge, and hence precipitates neuropathic pain.
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Activation of metabotropic glutamate receptors (mGluRs) has diverse effects on the functioning of vertebrate synapses. The cellular mechanisms that underlie these changes, however, are largely unknown. The role of presynaptic mGluRs in modulating Ca(2+) dynamics and regulating neurotransmitter release was investigated at the vestibulospinal-reticulospinal (VS-RS) synapse in the lamprey brain stem. ⋯ These results demonstrate the presence of presynaptic Group I mGluRs at the VS-RS synapse. Activation of these receptors leads to a rise in [Ca(2+)](i) and enhances the spontaneous and evoked release of glutamate. Taken together, these studies highlight the importance of synaptic activation of these facilitatory autoreceptors in both short-term plasticity and synaptic transmission.
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The effects of dopamine (DA) on a persistent Na(+) current (I(NaP)) in layer V-VI prefrontal cortical (PFC) pyramidal cells were studied using whole cell voltage-clamp recordings in rat PFC slices. After blocking K(+) and Ca (2+) currents, a tetrodotoxin-sensitive I(NaP) was activated by slow depolarizing voltage ramps or voltage steps. DA modulated the I(NaP) in a voltage-dependent manner: increased amplitude of I(NaP) at potentials more negative than -40 mV, but decreased at more positive potentials. ⋯ This was associated with a shift in the start of nonlinearity in the slope resistance to more negative membrane potentials. We proposed that this effect is due to a D1/D5 agonist-induced leftward shift in the activation of I(NaP). This enables DA to facilitate the firing of PFC neurons in response to depolarizing inputs.
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Intracellular recordings, ATP and cytosolic calcium measurements from CA1 pyramidal cells in rat hippocampal slices were used to examine the mechanisms by which temperature alters hypoxic damage. Hypothermia (34 degrees C) preserved ATP (1.7 vs. 0.8 nM/mg) and improved electrophysiologic recovery of the CA1 neurons after hypoxia; 58% of the neurons subjected to 10 min of hypoxia (34 degrees C) recovered their resting and action potentials, while none of the neurons at 37 degrees C recovered. Increasing the glucose concentration from 4 to 6 mM during normothermic hypoxia improved ATP (1.3 vs. 0.8 nM/mg) and mimicked the effects of hypothermia; 67% of the neurons recovered their resting and action potentials. ⋯ Increasing the glucose concentration from 4 to 8 mM during 10 min of hyperthermic hypoxia improved ATP (1.4 vs. 0.6 nM/mg), Ca(2+) (267 vs. 538 nM), and electrophysiologic recovery (90 vs. 0%). Our results indicate that the changes in electrophysiologic recovery with temperature are primarily due to changes in ATP and that the changes in depolarization and Ca(2+) are secondary to these ATP changes. Both primary and secondary changes are important for explaining the improved electrophysiologic recovery with hypothermia.