Brain research
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Comparative Study
Strain and sex differences in the expression of nociceptive behavior and stress-induced analgesia in rats.
Evidence indicates that genetic, gender, and emotional/attentional aspects modulate the pain sensation. The present study examined the effect of swim-stress on nociceptive responses in Lewis (LEW) and spontaneously hypertensive (SHR) inbred rats (contrasting for anxiety-related behaviors), as well as in Wistar (WIS) rats of both sexes. Furthermore, we explored possible neurochemical mechanisms involved. ⋯ The present results demonstrate genetic and gender differences in nociceptive sensitivity and in the activation of endogenous analgesic systems in rats and highlight the influence of emotional reactivity. The SHR's hypoalgesic phenotype seems to involve central cognitive processes. Therefore, the LEW and SHR inbred strains may provide an important tool for study of the molecular bases underlying nociception and its modulation and the relationship with emotional/attentional processes.
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Accumulating evidence indicates that neurite degeneration occurs via a distinct mechanism from somal death programs. We have previously shown that neuritic ATP level in sympathetic neurons decreases, whereas somal ATP level remains unaltered during degeneration caused by the microtubule-disrupting agent, vinblastine. Moreover, caspase activation occurs only in cell soma, supporting the view of somal apoptosis and neuritic necrosis. ⋯ The commitment time for the saving effect of TLCK occurred around 7 h following treatment with vinblastine, at a time point after microtubule degradation (2 h) and before massive beading formation (later than 12 h). Moreover, TLCK was also capable of suppressing Wallerian degeneration in culture and neuritic degeneration following withdrawal of NGF in a dose-dependent manner. These results strongly suggest that TLCK intervenes in a common step in the cascade of neuritic degeneration caused by these different experimental paradigms and provides a helpful clue for identifying such a molecular step.
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Human bone marrow stromal cells (hMSCs) enhance neurological recovery after stroke in rodents, possibly via induction of growth factors. We therefore elected to test the effects of hMSC treatment on insulin-like growth factor 1 (IGF-1), which plays an important role in growth, development, neuroprotection and repair in the adult. Rats (n=57) were subjected to permanent middle cerebral artery occlusion (MCAo) and injected intravenously with 3 x 10(6) hMSCs or phosphate-buffered saline (PBS) at 1 day after MCAo. ⋯ MAB1281-labeled hMSCs entered the ischemic brain and increased time-dependently. hMSC treatment significantly increased IGF-1 mRNA and BrdU(+), DCX(+), IGF-1(+) and IGF-1R(+) cells compared to PBS-treated rats (p<0.05). The percentage of BrdU(+) or DCX(+) cells colocalized with IGF-1 increased in the hMSC-treated rats compared to the PBS-treated rats (p<0.05). IGF-1 and IGF-1R may contribute to improved functional recovery and increased neurogenesis after treatment of stroke with hMSCs.
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Opioids are effective topical analgesics in the radiant heat tailflick assay and display synergistic interactions with a number of other classes of drugs. To determine whether these actions extend to other types of nociception, we examined the actions of topical morphine and lidocaine in a tail formalin assay in the mouse. Formalin responses in the tail were similar to those seen in the hind paw, but were limited to licking. ⋯ These studies validate the formalin assay in the tail and support the topical actions of opioids and other drugs in a second pain model. They also suggest supra-additive interactions between morphine and lidocaine similar to those previously seen. The tail formalin assay will be valuable in assessing the activity of topical drugs.
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Voltage-activated Na+ channels in the primary sensory neurons are important for generation of action potentials and regulation of neurotransmitter release. The Na+ channels expressed in different types of dorsal root ganglion (DRG) neurons are not fully known. In this study, we determined the possible difference in tetrodotoxin-sensitive (TTX-S) and -resistant (TTX-R) Na+ channel currents between isolectin B4 (IB4)-positive and IB4-negative small DRG neurons. ⋯ TTX had no effect on the evoked action potential in IB4-positive neurons, but it inhibited the action potential generation in about 50% IB4-negative neurons. This study provides complementary new information that there is a distinct difference in the expression level of TTX-S and TTX-R Na+ channels between IB4-negative than IB4-positive small-diameter DRG neurons. This difference in the density of TTX-R Na+ channels is responsible for the distinct membrane properties of these two types of nociceptive neurons.