Mostrando postagens com marcador Chronic pain. Mostrar todas as postagens
Mostrando postagens com marcador Chronic pain. Mostrar todas as postagens

quinta-feira, 15 de janeiro de 2015

Study reveals lack of data on opioid drugs for chronic pain

 

A National Institutes of Health white paper that was released today finds little to no evidence for the effectiveness of opioid drugs in the treatment of long-term chronic pain, despite the explosive recent growth in the use of the drugs.

The paper, which constitutes the final report of a seven-member panel convened by the NIH last September, finds that many of the studies used to justify the prescription of these drugs were either poorly conducted or of an insufficient duration.

An NIH white paper finds little to no evidence for the effectiveness of opioid drugs in the treatment of long-term chronic pain.

That makes prolific use of these drugs surprising, says Dr. David Steffens, chair of the psychiatry department at UConn Health and one of the authors of the study. When it comes to long-term pain, he says, "there's no research-based evidence that these medicines are helpful."

Yet despite this, prescriptions for opioid drugs (also known as opiate drugs; the two terms are technically distinct, but most physicians use them interchangeably) have more than tripled in the past 20 years, with more than 219 million prescriptions written in 2011, according to the study.

At the same time, the abuse of these drugs has also skyrocketed, leading some to refer to prescription drug abuse as an epidemic. More than 16,000 people died from prescription opioid overdoses in 2012, according to the Centers for Disease Control, and drug overdose now causes more deaths than motor vehicle accidents for people ages 25-64.

This level of opioid use and abuse is unprecedented in the world: the United States, with just 4.6 percent of the world's population, consumes 80 percent of the world's opioid drugs. That, says Steffens, makes this "a peculiarly American problem."

Steffens, like the other members of the panel, was surprised by many of these findings, since he is not an expert in opioid drugs, in drug abuse, or in pain management. The members of the panel were experienced clinicians with expertise in other areas; Steffens' specialty is geriatric psychiatry. "The NIH intentionally invited people from other fields of medicine," he says, "in order to avoid potential conflicts of interest, and to get a fresh perspective on the issue."

Over two days, the panel listened to evidence presented by an outside agency, which had conducted an exhaustive search of all the available studies about the use of opioid drugs. The panel's draft report was made available for public comment late last fall. The final report is published in the Annals of Internal Medicine.

Steffens notes that one of the great challenges in grappling with this issue is the fact that opioid drugs clearly are an effective treatment for some people dealing with pain, but it is hard to predict where trouble will crop up. Part of the problem, he points out, is the need for better communication about best practices to physicians who are prescribing these drugs.

"There are certain syndromes, like fibromyalgia, where opioids are less likely to be effective and patients are more likely get into trouble with abuse," says Steffens.

Another issue both for patients and for society at large is that pills from the pharmacy don't always end up in the hands they were prescribed for. The process of medicine being sold or given away (known as diversion) has long been identified as a key driver in the rise of prescription drug abuse.

Says Steffens, "I wish that doctors treating people for sports or workplace injuries would be cautious with the amount of pills they dispense."


Story Source:

The above story is based on materials provided by University of Connecticut. The original article was written by Tim Miller. Note: Materials may be edited for content and length.


Journal Reference:

  1. David B. Reuben, Anika A. H. Alvanzo, Takamaru Ashikaga, G. Anne Bogat, Christopher M. Callahan, Victoria Ruffing, David C. Steffens. National Institutes of Health Pathways to Prevention Workshop: The Role of Opioids in the Treatment of Chronic Pain. Annals of Internal Medicine, 2015; DOI: 10.7326/M14-2775

 

quinta-feira, 22 de maio de 2014

New target for chronic pain treatment found

 

May 21/ 2014

University of North Carolina Health Care

The enzyme PIP5K1C controls the activity of cellular receptors that signal pain, researchers have found. By reducing the enzyme, researchers showed that levels of a lipid called PIP2 is also lessened. They also found a compound that can dampen the activity of PIP5K1C. These findings could lead to a new kind of pain reliever for the more than 100 million people who suffer from chronic pain in the US.


Pain is signaled from the place of injury to the dorsal root ganglia – clusters of neurons alongside the spinal cord – before the pain is signaled into the spinal cord and finally the brain. Mark Zylka, PhD, has found a way to lessen the signal – and thus pain – at the dorsal root ganglia.

Researchers at the UNC School of Medicine have found a new target for treating chronic pain: an enzyme called PIP5K1C. In a paper published today in the journal Neuron, a team of researchers led by Mark Zylka, PhD, Associate Professor of Cell Biology and Physiology, shows that PIP5K1C controls the activity of cellular receptors that signal pain.

By reducing the level of the enzyme, researchers showed that the levels of a crucial lipid called PIP2 in pain-sensing neurons is also lessened, thus decreasing pain.

They also found a compound that could dampen the activity of PIP5K1C. This compound, currently named UNC3230, could lead to a new kind of pain reliever for the more than 100 million people who suffer from chronic pain in the United States alone.

In particular, the researchers showed that the compound might be able to significantly reduce inflammatory pain, such as arthritis, as well as neuropathic pain -- damage to nerve fibers. The latter is common in conditions such as shingles, back pain, or when bodily extremities become numb due to side effects of chemotherapy or diseases such as diabetes.

The creation of such bodily pain might seem simple, but at the cellular level it's quite complex. When we're injured, a diverse mixture of chemicals is released, and these chemicals cause pain by acting on an equally diverse group of receptors on the surface of pain-sensing neurons.

"A big problem in our field is that it is impractical to block each of these receptors with a mixture of drugs," said Zylka, the senior author of the Neuron article and member of the UNC Neuroscience Center. "So we looked for commonalities -- things that each of these receptors need in order to send a signal." Zylka's team found that the lipid PIP2 (phosphatidylinositol 4,5-bisphosphate) was one of these commonalities.

"So the question became: how do we alter PIP2 levels in the neurons that sense pain?" Zylka said. "If we could lower the level of PIP2, we could get these receptors to signal less effectively. Then, in theory, we could reduce pain."

Many different kinases can generate PIP2 in the body. Brittany Wright, a graduate student in Zylka's lab, found that the PIP5K1C kinase was expressed at the highest level in sensory neurons compared to other related kinases. Then the researchers used a mouse model to show that PIP5K1C was responsible for generating at least half of all PIP2 in these neurons.

"That told us that a 50 percent reduction in the levels of PIP5K1C was sufficient to reduce PIP2 levels in the tissue we were interested in -- where pain-sensing neurons are located" Zylka said. "That's what we wanted to do -- block signaling at this first relay in the pain pathway."

Once Zylka and colleagues realized that they could reduce PIP2 in sensory neurons by targeting PIP5K1C, they teamed up with Stephen Frye, PhD, the Director of the Center for Integrative Chemical Biology and Drug Discovery at the UNC Eshelman School of Pharmacy.

They screened about 5,000 small molecules to identify compounds that might block PIP5K1C. There were a number of hits, but UNC3230 was the strongest. It turned out that Zylka, Frye, and their team members had come upon a drug candidate. They realized that the chemical structure of UNC3230 could be manipulated to potentially turn it into an even better inhibitor of PIP5K1C. Experiments to do so are now underway at UNC.


Story Source:

The above story is based on materials provided by University of North Carolina Health Care. Note: Materials may be edited for content and length.


Journal Reference:

  1. Brittany D. Wright, Lipin Loo, Sarah E. Street, Anqi Ma, Bonnie Taylor-Blake, Michael A. Stashko, Jian Jin, William P. Janzen, Stephen V. Frye, Mark J. Zylka. The Lipid Kinase PIP5K1C Regulates Pain Signaling and Sensitization. Neuron, 2014; 82 (4): 836 DOI: 10.1016/j.neuron.2014.04.006