Background: Primary afferent nociceptor sensitization and its accompanying spontaneous discharge are believed to be the proximate cause of the spontaneous pain and hypersensitivity that follow an acute tissue injury. Evidence for this comes almost entirely from studies limited to the first few minutes to an hour or two after injury, when the inflammatory reaction to injury has just begun. However, there is evidence that inflammatory pain mechanisms differ from acute pain mechanisms and that the mechanisms that drive and modulate inflammatory pain may evolve over time.
Methods: The authors surveyed spontaneous afferent discharge in rats with hind paw inflammation evoked by complete Freund adjuvant over the entire 14 days of the inflammatory pain condition, as determined in parallel experiments assessing allodynia and hyperalgesia.
Results: Inflammation-evoked heat hyperalgesia, mechanoallodynia, and mechanohyperalgesia began within hours, persisted until at least day 7, and resolved by day 14. A large percentage (23%) of A fibers had spontaneous discharge 2 days after inflammation, but the incidence was much reduced (to 7-9%) by 7 and 14 days. At all times, the A-fiber discharge frequency was low (<3.0 Hz) or very low (<0.3 Hz). A large percentage (24%) of C fibers had spontaneous discharge 2 and 7 days after inflammation, but this also declined to near control levels by day 14; C-fiber discharge frequency was also always low (most at 0.3-1.0 Hz). 相似文献
The early maintenance of long-term potentiation (LTP) was studied in the CA1 region of hippocampal slices from 12- to 18-day-old rats in a low-magnesium solution (0.1 mM). The α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor-mediated components of the field excitatory postsynaptic potential were estimated in parallel using early and late measurements of the composite potential. At the normal test stimulus frequency of 0.1 Hz, LTP was seen initially as a predominant increase in the AMPA component, but converted, via a substantial decay of this component and a gradual growth of the NMDA component, into nearly equal changes of the two components. Interrupting the test stimulation for 10 min, changing the test stimulus frequency to 1/60 Hz after LTP induction, or using a test stimulus frequency of 1/60 Hz during the entire experiment significantly reduced the decay of the potentiation of the AMPA component while enhancing the potentiation of the NMDA one. The ratio between the magnitudes of the two excitatory postsynaptic potential (EPSP) components showed a decaying time course that was independent of the manipulations used. Application of the NMDA antagonist D(-)-2-amino-5-phosphonopentanoic acid (50μM) after LTP induction stabilized the LTP of the AMPA component until washout was started. On the other hand, the phosphatase inhibitor okadaic acid (1 μM) resulted in decay of the potentiation of both EPSP components back to around baseline and altered the time course of the ratio between the components. Our results show that the early maintenance of LTP is controlled in an activity-dependent and NMDA-dependent manner. This process accelerates the decay of LTP of both AMPA and NMDA components in parallel, suggesting that it is similar to homosynaptic long-term depression, although it operates at the normal test stimulus frequency. The data support a scenario in which LTP ensues as a selective AMPA receptor modification and subsequently converts to another modification, possibly a presynaptic one. 相似文献
The promoting effect of the Chinese medicinal herb, Wikstroemia chamaedaphne and Tung oil extracts (WC and HHPA) on carcinoma of uterine cervix induced by HSV-2 or MCA in mice was studied. The results showed that WC and HHPA extracts were not carcinogenic themselves. After carcinogen HSV-2 and MCA treatment, WC and HHPA were added separately. The inducing rates by HSV-2 increased from 7.4% to 21.1% and 26.3%, those by MCA increased from 56.5% to 82.8% and 84.4%. There was a significant difference between the combined groups and groups with HSV-2 or MCA only. The experimental results suggest that these two kinds of extracts play a promoting effect on carcinogenesis. The relation between the carcinogenesis of uterine cervix or nasopharynx and WC or HHPA extracts is discussed. 相似文献
The beta-adrenoceptor (beta-AR)-stimulatory guanine nucleotide-binding (Gs) protein system has been shown to play important roles in the cardiovascular system. The gene encoding the alpha-subunit of Gs proteins (GNAS1) is a candidate genetic determinant for hypertension. Because alcohol consumption is known to affect blood pressure partly through the beta-AR-Gs protein system, we examined the possible interaction between GNAS1 T393C polymorphism and drinking status in the association with hypertension in the present study. As a result, a non-significant but reasonable trend supporting the presence of an interaction was shown (p = 0.076). In line with this trend, the T393C polymorphism significantly interacted with drinking status in the association with systolic blood pressure (p = 0.028). Moreover, supporting the presence of an interaction, T allele carriers consistently had a higher probability of hypertension, higher systolic blood pressure, and higher diastolic blood pressure than CC homozygotes in non-drinkers and light drinkers. In contrast, CC homozygotes consistently had a higher probability of hypertension, higher systolic blood pressure, and higher diastolic blood pressure than T allele carriers in moderate to heavy drinkers. The present study also showed a significant interaction between the T393C polymorphism and drinking status in the association with pulse pressure (p = 0.026), reflected by a significant association between the T393C polymorphism and pulse pressure in moderate to heavy drinkers (p = 0.026). These findings may be helpful in conducting further molecular and biological studies on the relationship among the effects of alcohol, the beta-AR-Gs protein system, and hypertension. 相似文献