Journal of neurophysiology
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Primary and metastatic cancers that effect bone are frequently associated with pain. Sensitization of primary afferent C nociceptors innervating tissue near the tumor likely contributes to the chronic pain and hyperalgesia accompanying this condition. This study focused on the role of the endogenous peptide endothelin-1 (ET-1) as a potential peripheral algogen implicated in the process of cancer pain. ⋯ Whereas ET-1 produced sensitization of C nociceptors to heat stimuli in control mice, C nociceptors in tumor-bearing mice were sensitized to heat, and their responses were not further increased by ET-1. Importantly, administration of BQ-123 attenuated tumor-evoked sensitization of C nociceptors to heat. We conclude that ET-1 at the tumor site contributes to tumor-evoked excitation and sensitization of C nociceptors through an ETA receptor mediated mechanism.
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The supratrigeminal region (SupV) receives abundant orofacial sensory inputs and descending inputs from the cortical masticatory area and contains premotor neurons that target the trigeminal motor nucleus (MoV). Thus it is possible that the SupV is involved in controlling jaw muscle activity via sensory inputs during mastication. We used voltage-sensitive dye, laser photostimulation, patch-clamp recordings, and intracellular biocytin labeling to investigate synaptic transmission from the SupV to jaw-closing and jaw-opening motoneurons in the MoV in brain stem slice preparations from developing rats. ⋯ Gramicidin-perforated and whole cell patch-clamp recordings from masseter motoneurons (MMNs) and digastric motoneurons (DMNs) revealed that glycinergic and GABAergic postsynaptic responses evoked in MMNs and DMNs by SupV stimulation were excitatory in P1-P4 neonatal rats and inhibitory in P9-P12 juvenile rats, whereas glutamatergic postsynaptic responses evoked by SupV stimulation were excitatory in both neonates and juveniles. Furthermore, the axons of biocytin-labeled SupV neurons that were antidromically activated by MoV stimulation terminated in the MoV. Our results suggest that inputs from the SupV excite MMNs and DMNs through activation of glutamate, glycine, and GABAA receptors in neonates, whereas glycinergic and GABAergic inputs from the SupV inhibit MMNs and DMNs in juveniles.
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Individual primary vestibular afferents exhibit spontaneous activity the regularity of which can vary from regular to irregular. Different aspects of vestibular responsiveness have been associated with this dimension of regularity of resting discharge. Isolated rat vestibular ganglion cells (VGCs) showed heterogeneous intrinsic firing properties during sustained membrane depolarization: some neurons exhibited a strong adaptation generating just a single or a few spikes (phasic type), whereas other neurons showed moderate adaptation or tonic firing (tonic type). ⋯ Tetraethylammonium decreased the number of spikes during step current stimuli in all types. Blockade of Ca2+-activated K+ channels decreased the number of spikes in tonic VGCs. Our results suggest that Kv1 channels are critical both in determining the pattern of spike discharge in rat vestibular ganglion neurons and in their proportional change during maturation.
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Previous studies in anesthetized animals reported that the primary auditory cortex (A1) showed homogenous phasic responses to FM tones, namely a transient response to a particular instantaneous frequency when FM sweeps traversed a neuron's tone-evoked receptive field (TRF). Here, in awake cats, we report that A1 cells exhibit heterogeneous FM responses, consisting of three patterns. The first is continuous firing when a slow FM sweep traverses the receptive field of a cell with a sustained tonal response. ⋯ These peaks were not predictable from the cell's tonal response but reliably reflected the time when FM swept across specific frequencies. Our A1 samples often exhibited a complex response pattern, combining two or three of the basic patterns above, resulting in a heterogeneous response population. The diversity of FM responses suggests that A1 use multiple mechanisms to fully represent the whole range of FM parameters, including frequency extent, sweep speed, and direction.
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Although laser-evoked electroencephalographic (EEG) responses are increasingly used to investigate nociceptive pathways, their functional significance remains unclear. The reproducible observation of a robust correlation between the intensity of pain perception and the magnitude of the laser-evoked N1, N2, and P2 responses has led some investigators to consider these responses a direct correlate of the neural activity responsible for pain intensity coding in the human cortex. Here, we provide compelling evidence to the contrary. ⋯ We showed that increasing the temporal expectancy of the stimulus through stimulus repetition at a constant interstimulus interval 1) significantly reduces the magnitudes of the laser-evoked N1, N2, P2, and ERS; and 2) disrupts the relationship between the intensity of pain perception and the magnitude of these responses. Taken together, our results indicate that laser-evoked EEG responses are not determined by the perception of pain per se, but are mainly determined by the saliency of the eliciting nociceptive stimulus (i.e., its ability to capture attention). Therefore laser-evoked EEG responses represent an indirect readout of the function of the nociceptive system.