Pain
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Toll-like receptors (TLRs) play a pivotal role in inflammatory processes, and individual TLRs have been investigated in nociception. We examined overlapping and diverging roles of spinal TLRs and their associated adaptor proteins in nociceptive processing. Intrathecal (IT) TLR2, TLR3, or TLR4 ligands (-L) evoked persistent (7-day) tactile allodynia (TA) that was abolished in respective TLR-deficient mice. ⋯ Hence, spinal TIR domain-containing adaptor protein (TIRAP) and TRIF cascades differentially lead to robust TA by TNF-dependent and independent pathways, whereas activation of TRIF modulated processing through type I IFN receptors. Based on these results, we believe that processes leading to the activation of these spinal TLRs initiate TNF-dependent and -independent cascades, which contribute to the associated persistent pain state. In addition, TRIF pathways are able to modulate the TNF-dependent pain state through IFNβ.
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Comparative Study
Noxious stimulation excites serotonergic neurons: a comparison between the lateral paragigantocellular reticular and the raphe magnus nuclei.
The present study was designed to record electrophysiological responses to graded noxious thermal stimuli of serotonergic and nonserotonergic neurons in the lateral paragigantocellular reticular (LPGi) and the raphe magnus (RMg) nuclei in rats. All of the neurons recorded were juxtacellularly filled with neurobiotin and identified with double immunofluorescent labeling for both neurobiotin and serotonin. Under halothane anesthesia (0.75%), noxious thermal stimuli ⩾48°C activated almost all (88%) of the serotonergic neurons located within the LPGi (n=16). ⋯ Recording of serotonergic neurons in the RMg (n=21) demonstrated that the proportion of strongly activated (>2spike/s) neurons (19% vs 59% for the LPGi) as well as the magnitude of the activation (2.1±0.4spike/s: mean of responses above the population median) to thermal noxious stimuli were significantly lower than in the LPGi (P<.05). Within the boundaries of both the LPGi and the RMg (B3 group), nonserotonergic neurons were also predominantly excited (75%) by noxious stimuli, and the resulting activation (7.9±1.2spike/s) was even greater than that of serotonergic neurons. Thermal noxious stimuli-induced activation of LPGi serotonergic cells probably plays a key role in serotonin-mediated modulations of cardiac baroreflex and transmission of nociceptive messages occurring under such intense noxious conditions.
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Review Meta Analysis
Intravenous acetaminophen reduces postoperative nausea and vomiting: a systematic review and meta-analysis.
Prophylactic administration of IV paracetamol reduces post-operative nausea and vomiting, primarily through improved post-operative analgesia.
pearl -
Factors underlying individual differences in pain responding are incompletely understood, but are likely to include genetic influences on basal pain sensitivity in addition to demographic characteristics such as age, sex, and ethnicity, and psychological factors including personality. This study sought to explore the relationship between personality traits and experimental pain sensitivity, and to determine to what extent the covariances between these phenotypes are mediated by common genetic and environmental factors. A sample composed of 188 twins, aged 23 to 35years, was included in the study. ⋯ In contrast, associations between HPI and personality seemed weak and unstable, but a significant effect of Angry Hostility (a facet of Neuroticism) emerged in generalized estimating equations analysis. Although the genetic correlation between these phenotypes was essentially zero, a weak but significant individual-specific environmental correlation emerged (re=.21, P<.05). Taken together, these findings suggest that CPI is more consistently related to personality dispositions than HPI, both phenotypically and genetically.