Frontiers in physiology
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Frontiers in physiology · Jan 2012
Development of inflammation-induced hyperalgesia and allodynia is associated with the upregulation of extrasynaptic AMPA receptors in tonically firing lamina II dorsal horn neurons.
Persistent peripheral inflammation changes AMPA receptor (AMPAR) trafficking in dorsal horn neurons by promoting internalization of GluR2-containing, Ca(2+)-impermeable AMPARs from the synapses and by increasing insertion of GluR1-containing, Ca(2+)-permeable AMPARs in extrasynaptic plasma membrane. These changes contribute to the maintenance of persistent inflammatory pain. However, much less is known about AMPAR trafficking during development of persistent inflammatory pain and direct studies of extrasynaptic AMPARs functioning during this period are still lacking. ⋯ This upregulation was manifested as a robust increase in the amplitude of AMPAR-mediated currents 2-3 h post-CFA. These changes were observed specifically in SG neurons characterized by intrinsic tonic firing properties, but not in those that exhibited strong adaptation. Our results indicate that CFA-induced inflammation increases functional expression of extrasynaptic AMPARs in tonically firing SG neurons during development of pain hypersensitivity and that this increase may contribute to the development of peripheral persistent pain.
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Frontiers in physiology · Jan 2012
Predifferentiated GABAergic neural precursor transplants for alleviation of dysesthetic central pain following excitotoxic spinal cord injury.
Intraspinal quisqualic acid (QUIS) injury induce (i) mechanical and thermal hyperalgesia, (ii) progressive self-injurious overgrooming of the affected dermatome. The latter is thought to resemble painful dysesthesia observed in spinal cord injury (SCI) patients. We have reported previously loss of endogenous GABA immunoreactive (IR) cells in the superficial dorsal horn of QUIS rats 2 weeks post injury. ⋯ Surviving grafted GABA-IR NPCs were NeuN(+) and GFAP(-). These results indicate that partially differentiated NPCs survive and differentiate in vivo into neuronal cells following transplantation into an injured spinal cord. GABA-IR NPC transplants can restore lost dorsal horn inhibitory signaling and are useful in alleviating central pain following SCI.
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Frontiers in physiology · Jan 2012
Scale-Free and Multifractal Time Dynamics of fMRI Signals during Rest and Task.
Scaling temporal dynamics in functional MRI (fMRI) signals have been evidenced for a decade as intrinsic characteristics of ongoing brain activity (Zarahn et al., 1997). Recently, scaling properties were shown to fluctuate across brain networks and to be modulated between rest and task (He, 2011): notably, Hurst exponent, quantifying long memory, decreases under task in activating and deactivating brain regions. In most cases, such results were obtained: First, from univariate (voxelwise or regionwise) analysis, hence focusing on specific cognitive systems such as Resting-State Networks (RSNs) and raising the issue of the specificity of this scale-free dynamics modulation in RSNs. ⋯ Further, results indicate that most fMRI signals appear multifractal at rest except in non-cortical regions. Task-related modulation of multifractality appears only significant in functional networks and thus can be considered as the key property disentangling functional networks from artifacts. These finding are discussed in the light of the recent literature reporting scaling dynamics of EEG microstate sequences at rest and addressing non-stationarity issues in temporally independent fMRI modes.
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Frontiers in physiology · Jan 2012
Impact of blunted perception of dyspnea on medical care use and expenditure, and mortality in elderly people.
Dyspnea is an alarming symptom responsible for millions of patient visits each year. Poor perception of dyspnea might be reasonably attributed to an inappropriately low level of fear and inadequate earlier medical treatment for both patients and physicians, resulting in subsequent intensive care. This study was conducted to evaluate medical care use and cost, and mortality according to the perception of dyspnea in community-dwelling elderly people. ⋯ With low perception group as reference, the hazard ratios of all-cause mortality were 0.65 (95% CI 0.23-1.89) for intermediate perception group and 0.31 (0.10-0.97) for high perception group, indicating the mortality rate also significantly increased with the blunted perception of dyspnea after multivariates adjustment (p = 0.04). The blunted perception of dyspnea is related to hospitalization, large medical costs, and all-cause mortality in community-dwelling elderly people. These findings provide a rational for preventing serious illness with careful monitoring of objective conditions in the elderly.
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Frontiers in physiology · Jan 2012
Nociceptors as chronic drivers of pain and hyperreflexia after spinal cord injury: an adaptive-maladaptive hyperfunctional state hypothesis.
Spinal cord injury (SCI) causes chronic peripheral sensitization of nociceptors and persistent generation of spontaneous action potentials (SA) in peripheral branches and the somata of hyperexcitable nociceptors within dorsal root ganglia (DRG). Here it is proposed that SCI triggers in numerous nociceptors a persistent hyperfunctional state (peripheral, synaptic, and somal) that originally evolved as an adaptive response to compensate for loss of sensory terminals after severe but survivable peripheral injury. In this hypothesis, nociceptor somata monitor the status of their own receptive field and the rest of the body by integrating signals received by their peripheral and central branches and the soma itself. ⋯ Nociceptor activity generated above the injury level contributes to at- and above-level sensitization and pain (evoked and spontaneous). Thus, SCI triggers a potent nociceptor state that may have been adaptive (from an evolutionary perspective) after severe peripheral injury but is maladaptive after SCI. Evidence that hyperfunctional nociceptors make large contributions to behavioral hypersensitivity after SCI suggests that nociceptor-specific ion channels required for nociceptor SA and hypersensitivity offer promising targets for treating chronic pain and hyperreflexia after SCI.