Influence of Socioeconomic Status Trajectories on Innate Immune Responsiveness in Children

Lower socioeconomic status (SES) is consistently associated with poor health, yet little is known about the biological mechanisms underlying this inequality. In children, we examined the impact of early-life SES trajectories on the intensity of global innate immune activation, recognizing that excessive activation can be a precursor to inflammation and chronic disease.Stimulated interleukin-6 production, a measure of immune responsiveness, was analyzed ex vivo for 267 Canadian schoolchildren from a 1995 birth cohort in Manitoba, Canada. Childhood SES trajectories were determined from parent-reported housing data using a longitudinal latent-class modeling technique. Multivariate regression was conducted with adjustment for potential confounders.SES was inversely associated with innate immune responsiveness (p=0.003), with persistently low-SES children exhibiting responses more than twice as intense as their high-SES counterparts. Despite initially lower SES, responses from children experiencing increasing SES trajectories throughout childhood were indistinguishable from high-SES children. Low-SES effects were strongest among overweight children (p<0.01). Independent of SES trajectories, immune responsiveness was increased in First Nations children (p<0.05) and urban children with atopic asthma (p<0.01).These results implicate differential immune activation in the association between SES and clinical outcomes, and broadly imply that SES interventions during childhood could limit or reverse the damaging biological effects of exposure to poverty during the preschool years

Targeting TRPV1 as an Alternative Approach to Narcotic Analgesics to Treat Chronic Pain Conditions

In spite of intense research efforts and after the dedicated Decade of Pain Control and Research, there are not many alternatives to opioid-based narcotic analgesics in the therapeutic armamentarium to treat chronic pain conditions. Chronic opioid treatment is associated with sedation, tolerance, dependence, hyperalgesia, respiratory depression, and constipation. Since the affective component is an integral part of pain perception, perhaps it is inevitable that potent analgesics possess the property of impacting pain pathways in the supraspinal structures. The question still remains to be answered is that whether a powerful analgesic can be devoid of narcotic effect and addictive potentials. Local anesthetics are powerful analgesics for acute pain by blocking voltage-gated sodium channels that are involved in generation and propagation of action potentials. Antidepressants and anticonvulsants have proven to be useful in the treatment of certain modalities of pain. In neuropathic pain conditions, the complexity arises because of the notion that neuronal circuitry is altered, as occurs in phantom pain, in that pain is perceived even in the absence of peripheral nociceptive inputs. If the locus of these changes is in the central nervous system, commonly used analgesics may not be very useful. This review focuses on the recent advances in nociceptive transmission and nociceptive transient receptor potential vanilloid 1 channel as a target for treating chronic pain conditions with its agonists/antagonists