Brain : a journal of neurology
-
Using resting-state functional magnetic resonance imaging, spontaneous low-frequency fluctuations in the blood oxygenation level-dependent signal were measured to investigate connectivity between key brain regions hypothesized to be differentially affected in dementia with Lewy bodies compared with Alzheimer's disease and healthy controls. These included connections of the hippocampus, because of its role in learning, and parietal and occipital areas involved in memory, attention and visual processing. Connectivity was investigated in 47 subjects aged 60 years and over: 15 subjects with dementia with Lewy bodies, 16 subjects with Alzheimer's disease and 16 control subjects. ⋯ Consistent with the known relative preservation of memory in dementia with Lewy bodies compared with Alzheimer's disease, hippocampal connectivity was not found to be greater in dementia with Lewy bodies. Importantly, while metabolic imaging shows functional change in primary visual cortex in dementia with Lewy bodies, which is hypothesized to account for visual hallucinations, we found connectivity with this region to be unaffected. This implicates areas beyond visual sensory input level in the visual symptoms and visual-perceptual dysfunction seen in dementia with Lewy bodies.
-
Adult brain connectivity is shaped by the balance of sensory inputs in early life. In the case of pain pathways, it is less clear whether nociceptive inputs in infancy can have a lasting influence upon central pain processing and adult pain sensitivity. Here, we show that adult pain responses in the rat are 'primed' by tissue injury in the neonatal period. ⋯ Intrathecal minocycline at the time of adult injury selectively prevented both the hyperalgesia and early microglial reactivity associated with prior neonatal injury. The enhanced neuroimmune response seen in neonatally primed animals could also be demonstrated in the absence of peripheral tissue injury by direct electrical stimulation of tibial nerve fibres, confirming that centrally mediated mechanisms contribute to these long-term effects. These data suggest that early life injury may predispose individuals to enhanced sensitivity to painful events.
-
Painful diabetic neuropathy is a common complication of diabetes mellitus and can affect many aspects of life and severely limit patients' daily functions. Signals of painful diabetic neuropathy are believed to originate in the peripheral nervous system. However, its peripheral mechanism of hyperalgesia has remained elusive. ⋯ Delivery of low concentrations of tetrodotoxin and Nav1.8 selective blocker, A-803467 on the main axon of C-fibres was found to markedly enhance the conduction failure in a dose-dependent manner in diabetic rats. Upregulated expression of sodium channel subunits Nav1.7 and Nav1.8 in both small dorsal root ganglion neurons and peripheral C-fibres as well as enhanced transient and persistent sodium current and increased excitability in small dorsal root ganglion neurons from diabetic rats might underlie the reduced conduction failure in the diabetic high-firing-frequency polymodal nociceptive C-fibres. This study shed new light on the functional capability in the pain signals processing for the main axon of polymodal nociceptive C-fibres and revealed a novel mechanism underlying diabetic hyperalgesia.
-
Emerging evidence suggests that the suppressive modulators released from nociceptive afferent neurons contribute to pain regulation. However, the suppressive modulators expressed in small-diameter neurons of the dorsal root ganglion remain to be further identified. The present study shows that the activin C expressed in small dorsal root ganglion neurons is required for suppressing inflammation-induced nociceptive responses. ⋯ Intrathecally applied activin C could reduce nociceptive responses induced by formalin or complete Freund's adjuvant. Moreover, activin C was found to inhibit the inflammation-induced phosphorylation of extracellular signal-regulated kinase in the dorsal root ganglia and the dorsal spinal cord. Thus, activin C functions as an endogenous suppressor of inflammatory nociceptive transmission and may have a therapeutic potential for treatment of inflammatory pain.