Opioid Pharmacotherapy for Chronic Noncancer Pain: The American Experience.
Opioid pharmacotherapy for chronic noncancer pain: the american experience.
Filed under: Drug and Alcohol Rehabilitation
Korean J Pain. 2013 Jan; 26(1): 3-13
Chapman CR
Chronic noncancer pain is a significant and growing public health challenge in the United States. Lacking effective alternative interventions for effective chronic noncancer pain management, many physicians have turned to opioid pharmacotherapy. Increased opioid prescribing brings not only gains in therapeutic benefit but also a higher incidence of adverse drug events including increased medication misuse and opioid related mortality. Currently the United States must confront the dual problems of widespread undertreated chronic noncancer pain and a prescription opioid abuse crisis. Withholding pain relieving drugs from patients in need is unjustifiable, yet drug diversion, abuse and adverse drug events have become major social as well as medical problems. At the heart of this crisis is the lack of definitive evidence about the risk to benefit ratio of opioid pharmacotherapy for chronic noncancer pain both on an individual case and on a population basis. This article describes the extent and severity of the American chronic noncancer pain problem and the history of opioid pharmacotherapy for chronic noncancer pain in the United States. It then discusses the concept of evidence based practice and reviews current evidence supporting opioid pharmacotherapy for chronic noncancer pain as well as adverse drug events related to opioid pharmacotherapy including misuse and abuse. Finally, it considers the conflict of providing pain relief versus protecting society and reviews steps that governmental agencies, industry and others are taking to contain and ultimately resolve the problems of excessive prescribing and conflicting priorities.
HubMed – drug
Quercetin Enhances the Antitumor Activity of Trichostatin A through Upregulation of p53 Protein Expression In Vitro and In Vivo.
Filed under: Drug and Alcohol Rehabilitation
PLoS One. 2013; 8(1): e54255
Chan ST, Yang NC, Huang CS, Liao JW, Yeh SL
This study investigated the effects of quercetin on the anti-tumor effect of trichostatin A (TSA), a novel anticancer drug, in vitro and in vivo and the possible mechanisms of these effects in human lung cancer cells. We first showed that quercetin (5 µM) significantly increased the growth arrest and apoptosis in A549 cells (expressing wild-type p53) induced by 25 ng/mL of (82.5 nM) TSA at 48 h by about 25% and 101%, respectively. However, such enhancing effects of quercetin (5 µM) were not significant in TSA-exposed H1299 cells (a p53 null mutant) or were much lower than in A549 cells. In addition, quercetin significantly increased TSA-induced p53 expression in A549 cells. Transfection of p53 siRNA into A549 cells significantly but not completely diminished the enhancing effects of quercetin on TSA-induced apoptosis. Furthermore, we demonstrated that quercetin enhanced TSA-induced apoptosis through the mitochondrial pathway. Transfection of p53 siRNA abolished such enhancing effects of quercetin. However, quercetin increased the acetylation of histones H3 and H4 induced by TSA in A549 cells, even with p53 siRNA transfection as well as in H1299 cells. In a xenograft mouse model of lung cancer, quercetin enhanced the antitumor effect of TSA. Tumors from mice treated with TSA in combination with quercetin had higher p53 and apoptosis levels than did those from control and TSA-treated mice. These data indicate that regulation of the expression of p53 by quercetin plays an important role in enhancing TSA-induced apoptosis in A549 cells. However, p53-independent mechanisms may also contribute to the enhancing effect of quercetin.
HubMed – drug
Brief exposure to novel or enriched environments reduces sucrose cue-reactivity and consumption in rats after 1 or 30 days of forced abstinence from self-administration.
Filed under: Drug and Alcohol Rehabilitation
PLoS One. 2013; 8(1): e54164
Grimm JW, Weber R, Barnes J, Koerber J, Dorsey K, Glueck E
Environmental enrichment (EE) reduces drug and sucrose cue-reactivity in rats. In a previous study we reported that 1 month of EE (large cage, toys, and social cohorts) significantly reduced sucrose cue-reactivity. In the present study, we examined whether overnight (22 h) EE would be as effective. We also examined whether social enrichment (SE), enrichment alone (SoloEE), or exposure to an alternative environment (AEnv) might account for the EE effect. Rats self-administered 10% sucrose (.2 mL/delivery) in 10 daily 2-h sessions. Sucrose delivery was accompanied by a tone+light cue. Rats were then exposed to enrichment or alternative environment conditions overnight (acute) or for 29 days (chronic). Sucrose cue-reactivity was measured after this period of forced abstinence in a session identical to training, but no sucrose was delivered with the cue. All acute conditions markedly reduced sucrose cue-reactivity after 1 day of forced abstinence compared to single-housed rats in standard vivarium housing (CON). Sucrose consumption was also significantly reduced in all groups but SoloEE in a next-day test. All acute conditions but SE significantly reduced sucrose cue-reactivity when administered just prior to Day 30 of forced abstinence; all reduced sucrose consumption in a next-day test. All chronic conditions except for SE and AEnv significantly reduced sucrose cue-reactivity on the Day 30 test and sucrose consumption in a next day test. For both acute and chronic comparisons, EE manipulations were the most effective at reducing sucrose cue-reactivity and consumption. SoloEE and EE were equally effective at reducing sucrose cue-reactivity and similarly effective at reducing sucrose consumption. This indicates that social interaction is not a necessary condition for reducing sucrose-motivated behaviors. These results may be useful in the development of anti-relapse strategies for drug and food addictions.
HubMed – drug
Activation of p53 by Chemotherapeutic Agents Enhances Reovirus Oncolysis.
Filed under: Drug and Alcohol Rehabilitation
PLoS One. 2013; 8(1): e54006
Pan D, Marcato P, Ahn DG, Gujar S, Pan LZ, Shmulevitz M, Lee PW
Mammalian reovirus is a benign virus that possesses the natural ability to preferentially infect and kill cancer cells (reovirus oncolysis). Reovirus exploits aberrant Ras signalling in many human cancers to promote its own replication and spread. In vitro and in vivo studies using reovirus either singly or in combination with anti-cancer drugs have shown very encouraging results. Presently, a number of reovirus combination therapies are undergoing clinical trials for a variety of cancers. Previously we showed that accumulation of the tumor suppressor protein p53 by Nutlin-3a (a specific p53 stabilizer) enhanced reovirus-induced apoptosis, and resulted in significantly higher levels of reovirus dissemination. In this study, we examined the role of p53 in combination therapies involving reovirus and chemotherapeutic drugs. We showed that sub-lethal concentrations of traditional chemotherapy drugs actinomycin D or etoposide, but not doxorubicin, enhanced reovirus-induced apoptosis in a p53-dependent manner. Furthermore, NF-?B activation and expression of p53-target genes (p21 and bax) were important for the p53-dependent enhancement of cell death. Our results show that p53 status affects the efficacy of combination therapy involving reovirus. Choosing the right combination partner for reovirus and a low dosage of the drug may help to both enhance reovirus-induced cancer elimination and reduce drug toxicity.
HubMed – drug
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