Neuroscience
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Estrogen status is a risk factor in painful temporomandibular disorders (TMJD). Previously we reported that estradiol (E2) enhanced nociceptive processing of TMJ input by neurons in superficial laminae at the spinomedullary (Vc/C(1-2)) region; however, the mechanisms for this enhancement are not known. The present study determined if ionotropic glutamate receptors contribute to TMJ nociceptive processing in an E2-dependent manner. ⋯ Spontaneous activity of TMJ units was not influenced by AP5, whereas it was reduced by DNQX similarly in both groups. The high threshold convergent cutaneous receptive field area of TMJ units was not changed by AP5, whereas DNQX caused a significant reduction in both groups. These results suggest that NMDA-dependent mechanisms contribute to the enhanced ATP-evoked responses of TMJ units in superficial laminae at the Vc/C(1-2) region under high E2 conditions, while non-NMDA-dependent mechanisms modify the encoding properties of TMJ units independent of E2 status.
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Balance control depends on the interaction of multiple inputs originating from different sensory systems. Here, we investigated the effect on quiet human stance of changing the visual condition prior to a proprioceptive perturbation produced by vibration of dorsal neck muscles. In complete absence of visual references, the amplitude of the postural responses to neck vibration (forward shift of the centre of foot pressure) was the largest and became progressively larger as a function of the repetition of administered stimuli. ⋯ The fore-period must last more than 3 s in order to affect the response to neck muscle vibration. The responsiveness to a proprioceptive disturbing input does not immediately change on adding or subtracting vision, but a finite time period must elapse before the postural "set" defined by vision is fully established. The findings underline the importance of time when vision is used in re-weighting the excitability of the postural control mechanisms.
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Spinal cord microglial toll-like receptor 4 (TLR4) has been implicated in enhancing neuropathic pain and opposing morphine analgesia. The present study was initiated to explore TLR4-mediated pain modulation by intrathecal lipopolysaccharide, a classic TLR4 agonist. However, our initial study revealed that intrathecal lipopolysaccharide failed to induce low-threshold mechanical allodynia in naive rats, suggestive that TLR4 agonism may be insufficient to enhance pain. ⋯ In support of this allodynia being mediated via a TLR4/HSP90 pathway, it was prevented or reversed by intrathecal co-administration of a HSP90 inhibitor, a TLR4 inhibitor, a microglia/monocyte activation inhibitor (as monocyte-derived cells are the predominant cell type expressing TLR4), and interleukin-1 receptor antagonist (as this proinflammatory cytokine is a downstream consequence of TLR4 activation). Together, these results suggest for the first time that TLR4 activation is necessary but not sufficient to induce spinally mediated pain enhancement. Rather, the data suggest that TLR4-dependent pain phenomena may require contributions by multiple components of the TLR4 receptor complex.
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Effects of pregabalin (PGB, 20-80 mg/kg i.v. injection) on spinally-organized nociception were investigated in isoflurane-anesthetized intact and spinalized rats. Responses of single deep spinal dorsal horn (DH) (laminae IV-V) nociceptive-specific (NS) neurons receiving peripheral inputs from A-delta and C fibers to repetitive electrical stimulation (intensity: 3-5 mA; frequency: 1 Hz; pulse duration: 1 ms), mechanical/heat stimulation were recorded extracellularly during physiological condition and s.c. bee venom (BV) induced inflammation. PGB significantly inhibited C-fiber mediated spinal NS neurons' late responses including phenomena of wind-up (temporal summation) and after-discharge. ⋯ This suggests that PGB-induced selective antinociceptive effect on C-fiber mediated nociception is mainly central effects involving supraspinal centers via descending inhibitory controls. Furthermore, pre-treatment, but not post-treatment, with PGB (80 mg/kg) markedly inhibited s.c. BV elicited spontaneous neuronal responses, and noxious mechanical/heat stimuli evoked hyperactivities of spinal NS neurons, indicating that PGB has efficacy of pre-emptive analgesia on pathological pain associated with central sensitization.
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Recent findings highlight the participation of central glial cells in chronic pain, but less is known of a comparable role for satellite glial cells (SGCs), in dorsal root ganglia (DRG). Our previous work showed that sciatic nerve axotomy augmented SGC coupling by gap junctions. The aim of the present research was to find out whether similar changes occur in a mouse inflammation model. ⋯ This is the first evidence for ultrastructural changes in SGCs following inflammation. The results support the idea that SGCs are sensitive to a variety of peripheral nerve injuries. We propose that the observed changes may alter signal transmission in DRG and thus may contribute to chronic pain.