Journal of neurophysiology
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Comparative Study
Regional intensive and temporal patterns of functional MRI activation distinguishing noxious and innocuous contact heat.
Cortical responses to painful and nonpainful heat were measured using functional magnetic resonance imaging (fMRI) region of interest analysis (ROI) of primary somatosensory cortex (S1), secondary somatosensory cortex (S2), anterior cingulate (ACC), supplementary motor area (SMA), insula, and inferior frontal gyrus (IFG). Previous studies indicated that innocuous and noxious stimuli of different modalities produce responses with different time courses in S1 and S2. The aim of this study was to 1) determine whether temporally distinct nociceptive blood oxygen level-dependent (BOLD) responses are evoked in multiple somatosensory processing cortical areas and 2) whether these responses discriminate small noxious stimulus intensity differences. ⋯ Responses to innocuous and noxious stimuli were not statistically different in contralateral S2. In contralateral S1 only, the nociceptive response could differentiate heat stimuli separated by 1 degrees C. These results show that 1) multiple cortical areas have temporally distinguishable innocuous and noxious responses evoked by a painfully hot thermode, 2) the nociceptive processing properties vary across cortical regions, and 3) nociceptive responses in S1 discriminate between painful temperatures at a level unmatched in other cortical areas.
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Comparative Study
Kappa opioids inhibit physiologically identified medullary pain modulating neurons and reduce morphine antinociception.
Microinjection of kappa opioid receptor (KOR) agonists into the rostral ventromedial medulla (RVM) attenuates mu-opioid receptor mediated antinociception and stress-induced analgesia, yet is also reported to have an analgesic effect. To determine how KOR agonists produce both antinociceptive and antianalgesic actions within the RVM, the KOR agonist U69593 was microinjected directly into the RVM while concurrently monitoring tail flick latencies and RVM neuronal activity. Among RVM neurons recorded in vivo, two types show robust changes in activity just prior to the nocifensive tail flick reflex: ON cells burst just prior to a tail flick and their activity is pronociceptive, whereas OFF cells pause just prior to the tail flick and their activity is antinociceptive. ⋯ Furthermore, U69593 inhibited ongoing activity in subsets of OFF cells (4/11) and NEUTRAL cells (3/9). Microinjection of U69593 into the RVM also attenuated morphine antinociception and suppressed the excitation of off cells. Together with previous in vivo and in vitro studies, these results are consistent with the idea that KOR agonists can be either pronociceptive through direct inhibition of OFF cells, or antianalgesic through both postsynaptic inhibition and presynaptic inhibition of glutamate inputs to RVM OFF cells.
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Comparative Study
Estrogen and inflammation increase the excitability of rat temporomandibular joint afferent neurons.
Several painful conditions, including temporomandibular disorders (TMD), are more prevalent and more severe in women than in men. Although the physiological basis for this sex difference remains to be determined, it is likely that estrogen is an underlying factor. The present study was performed to test the hypotheses that estrogen increases the excitability of rat temporomandibular joint (TMJ) afferents and exacerbates the inflammation-induced sensitization of these sensory neurons. ⋯ The effects were additive with neurons from rats receiving both estrogen and inflammation being the most excitable. The increases in excitability were associated with changes in passive properties and action potential waveform, suggesting that estrogen and inflammation affect the expression and/or properties of ion channels in TMJ neurons. Importantly, the influence of estrogen on both baseline and inflammation-induced changes in TMJ neuronal excitability may help explain the profound sex difference observed in TMD as well as suggest a novel target for the treatment of this pain condition.
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Comparative Study
Spinal neurons that express NK-1 receptors modulate descending controls that project through the dorsolateral funiculus.
Selective ablation of spinal neurons possessing substance P receptors (NK-1 receptors) using the selective cytotoxin conjugate substance P-saporin (SP-SAP) decreases hyperalgesia and central sensitization. The mechanisms by which NK-1 expressing neurons modulate the excitability of other dorsal horn neurons are unclear. Because the majority of NK-1 expressing spinal neurons project rostrally, it is possible that they are part of a spinal-supraspinal circuitry that contributes to descending modulation of excitability of spinal nociceptive neurons. ⋯ In vehicle-treated rats, transection of the DLF caused a 233% increase in mean spontaneous activity of neurons and enhanced their responses to mechanical and heat stimuli, whereas these increases in excitation were blocked in rats pretreated with SP-SAP. Importantly, SP-SAP alone had no effect on spontaneous or evoked activity in the absence of DLF transection. These results demonstrate that spinal neurons expressing the NK-1 receptor appear to play a pivotal role in regulating descending systems that modulate activity of nociceptive dorsal horn neurons.
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Comparative Study
Functional properties of fast spiking interneurons and their synaptic connections with pyramidal cells in primate dorsolateral prefrontal cortex.
Recent studies suggest that fast-spiking (FS) interneurons of the monkey dorsolateral prefrontal cortex (DLPFC) exhibit task-related firing during working-memory tasks. To gain further understanding of the functional role of FS neurons in monkey DLPFC, we described the in vitro electrophysiological properties of FS interneurons and their synaptic connections with pyramidal cells in layers 2/3 of areas 9 and 46. Extracellular spike duration was found to distinguish FS cells from non-FS interneuron subtypes. ⋯ Repetitive FS neuron stimulation, partially mimicking the sustained firing of interneurons in vivo, produced short-term depression of the unitary IPSPs, present at connections made by both basket and chandelier neurons and due at least in part to presynaptic mechanisms. These results suggest that FS neurons and their synaptic connections with pyramidal cells have homogeneous physiological properties. Thus different functional roles of basket and chandelier neurons in the DLPFC in vivo must arise from the distinct properties of the interneuronal axonal arborization or from a different functional pattern of excitatory and inhibitory connections with other components of the DLPFC neuronal network.