Neuropathic and inflammatory antinociceptive effects and electrocortical changes produced by Salvia divinorum in rats.

Ethnopharmacological Relevance: Salvia divinorum is a medicinal plant traditionally used in hallucinogenic ethnopharmacological practices and for its analgesic and antinflammatory properties. Its active compounds include diterpenes known as salvinorins which act as potent κ opioid receptor agonists.

Aim Of The Study: Given its effects in acute animal models of pain, as well as its antinflammatory attributes, we decided to investigate the analgesic effects of an SD extract in neuropathic (sciatic loose nerve ligature) and inflammatory (intra plantar carrageenan) pain models in rats.

A D2-like receptor family agonist produces analgesia in mechanonociception but not in thermonociception at the spinal cord level in rats.

The administration of dopaminergic drugs produces analgesia in individuals experiencing different types of pain. Analgesia induced by these drugs at the spinal cord level is mediated by D2-like agonists, which specifically inhibit the detection of nociceptive stimuli by sensory afferents. The extent of the analgesia provided by spinal dopamine agonists remains controversial, and the cellular mechanism of this analgesic process is poorly understood.

Inflammatory nociception responses do not vary with age, but diminish with the pain history.

Some of the relevant factors that must be considered when dealing with old age include its growing numbers in the general population and pain contention in this age group. In this sense, it is important to study whether antinociceptive responses change with age. To elucidate this point, persistent pain in animals is the preferred model.

Inhibition of peripheral nociceptors by aminoglycosides produces analgesia in inflammatory pain models in the rat.

Aminoglycosides (AGs) modulate nociceptors and ionic channels expressed in sensory neurons. The AG applied in situ could be useful to alleviate hyperalgesia in animal models of inflammatory pain. We tested streptomycin (ST) and neomycin (NEO) as analgesic agents applied in situ in rat paw inflammation caused by formalin or carrageenan administration.

Taurine enhances antinociception produced by a COX-2 inhibitor in an inflammatory pain model.

The temporal activation of the sensory systems, especially in pain, determines intermediate states that define the future of the response to sensory stimulation. In this work, we interfere pharmacologically with those states that produce peripheral and central sensitisation after an acute inflammatory process, inhibiting at the periphery the COX-2 with celecoxib and using taurine (glycine A receptor agonist) for central pain relief. We tested the paw withdrawal reflex latencies to thermo- and mechanonociception after the induction of an acute inflammatory process with carrageenan.

Nras loss induces metastatic conversion of Rb1-deficient neuroendocrine thyroid tumor.

Mutations in the gene encoding the retinoblastoma tumor suppressor predispose humans and mice to tumor development. Here we have assessed the effect of Nras loss on tumor development in Rb1 heterozygous mice. Loss of one or two Nras alleles is shown to significantly reduce the severity of pituitary tumors arising in Rb1(+/-) animals by enhancing their differentiation.

Genetic interaction between Rb and K-ras in the control of differentiation and tumor suppression.

Although the retinoblastoma protein (pRb) has been implicated in the processes of cellular differentiation, there is no compelling genetic or in vivo evidence that such activities contribute to pRb-mediated tumor suppression. Motivated by cell culture studies suggesting that Ras is a downstream effector of pRb in the control of differentiation, we have examined the tumor and developmental phenotypes of Rb and K-ras double-knockout mice. We find that heterozygosity for K-ras (i) rescued a unique subset of developmental defects that characterize Rb-deficient embryos by affecting differentiation but not proliferation and (ii) significantly enhanced the degree of differentiation of pituitary adenocarcinomas arising in Rb heterozygotes, leading to their prolonged survival.

A mechanism of cyclin D1 action encoded in the patterns of gene expression in human cancer.

Here we describe how patterns of gene expression in human tumors have been deconvoluted to reveal a mechanism of action for the cyclin D1 oncogene. Computational analysis of the expression patterns of thousands of genes across hundreds of tumor specimens suggested that a transcription factor, C/EBPbeta/Nf-Il6, participates in the consequences of cyclin D1 overexpression. Functional analyses confirmed the involvement of C/EBPbeta in the regulation of genes affected by cyclin D1 and established this protein as an indispensable effector of a potentially important facet of cyclin D1 biology.

Rb and N-ras function together to control differentiation in the mouse.

The product of the retinoblastoma tumor suppressor gene (Rb) can control cell proliferation and promote differentiation. Murine embryos nullizygous for Rb die midgestation with defects in cell cycle regulation, control of apoptosis, and terminal differentiation of several tissues, including skeletal muscle, nervous system, and lens. Previous cell culture-based experiments have suggested that the retinoblastoma protein (pRb) and Ras operate in a common pathway to control cellular differentiation.