The senior investigator was Kenneth Hargreaves, D.D.S., Ph.D., professor and chair of the Department of Endodontics in the Dental School at the UT Health Science Center. Amol M. Patwardhan, M.B.B.S., Ph.D., a graduate of the Health Science Center’s Department of Pharmacology who worked under Dr. Hargreaves’ supervision, is the lead author.

"Nearly everyone will experience persistent pain at some point in their lifetime," Dr. Hargreaves said. "Our findings are truly exciting because they will offer physicians, dentists and patients more options in prescription pain medications. In addition, they may help circumvent the problem of addiction and dependency to pain medications, and will have the potential to benefit millions of people who suffer from chronic pain every day."

Pain has been called a "complex epidemic" in the United States. Nearly 50 million Americans live with chronic pain caused by disease or injury. Few physicians or dentists specialize in the field of pain medicine. With pain medication options largely limited to opioids (such as morphine) and aspirin-like drugs, some patients become addicted or dependent upon these drugs, or suffer side effects such as kidney or liver damage.

Researchers at the UT Health Science Center found a new family of fatty acids, produced by the body itself, that play an important role in the biology of pain.

"Capsaicin is an ingredient in hot chili peppers and causes pain by activating a receptor called transient potential vanilloid 1 (TRPV1). We started out seeking the answer to the question "Why is TRPV1 consistently activated in the body upon injury or painful heat? We wanted to know how skin cells talk to pain neurons," Dr. Hargreaves said. "What we found was much more surprising and exciting. We have discovered a family of endogenous capsaicin-like molecules that are naturally released during injury, and now we understand how to block these mechanisms with a new class of non-addictive therapies."

Researchers used flaps of skin from laboratory mice that were heated in a water bath at temperatures greater than 43 degrees Celsius. The degree of heat used was significant because the human body normally begins to feel discomfort and pain at 43 degrees Celsius and higher, Dr. Hargreaves noted.

TRPV1 resides on the membranes of pain- and heat-sensing neurons. When a person eats a hot chili pepper, for example, he immediately feels a burning sensation because the capsaicin, the primary ingredient in the chili pepper, has activated the TRPV1 protein in the pain neurons. In high concentrations, capsaicin can also cause a burning effect on other sensitive areas of the skin.

The fluid from the heated skin was then applied to sensory neurons cultured from two sets of laboratory mice, including one set of animals in which a gene was deleted or "knocked out." Neurons from the wild type (non-altered) mice were sensitive to capsaicin, the main ingredient in chili peppers. The neurons of the knockout mice, in which the TRPV1 gene was deleted, were not sensitive to capsaicin and were used as the control.

"We found that in the skin flaps heated at greater than 43 degrees Celsius, the cells’ pain neurons showed tremendous activity in the wild type, but not in neurons from mice that lacked TRPV1," Dr. Hargreaves said. He indicated that this novel phenomenon was taking place because the cells, in response to the heat, began to create their own natural endogenous capsaicins, which they later identified as a series of compounds or fatty acids called oxidized linoleic acid metabolites (OLAMs).

Linoleic acid is one of the most abundant fatty acids in the human body. Under conditions such as inflammation, low blood pressure and some other illnesses, linoleic acid is rapidly oxidized to form biologically active metabolites. However, little else is understood about these substances. The metabolites that were consistently seen in increased amounts in the mouse skin biopsies exposed to heat temperatures greater than 43 degrees Celsius are called 9- and 13-HODE (hydroxyoctadecadienoic acid).

"This is a major breakthrough in understanding the mechanisms of pain and how to more effectively treat it," Dr. Hargreaves said. "These data demonstrate, for the first time, that OLAMs constitute a new family of naturally occurring capsaicin-like agents, and may explain the role of these substances in many pain conditions. This hypothesis suggests that agents blocking either the production or action of these substances could lead to new therapies and pharmacological interventions for various inflammatory diseases and pain disorders such as arthritis, fibromyalgia and others, including pain associated with cancer."

The research has led Dr. Hargreaves’ team to develop two new classes of analgesics using drugs that either block the synthesis of OLAMs or antibodies that inactivate them. These drugs could eventually come in the form of a topical agent, or a pill or liquid that could be ingested, or in the form of an injection. Both approaches have the potential to block pain at its source, unlike opioid narcotics that travel to the brain and affect the central nervous system.

Co-authors of the study with Drs. Hargreaves and Patwardhan from the UT Health Science Center San Antonio are: Armen N. Akopian, Ph.D., assistant professor of endodontics; Anibal Diogenes, D.D.S., Ph.D., assistant professor of endodontics; Susan Weintraub, Ph.D., professor of biochemistry; Nikita Ruparel, D.D.S., Ph.D., a graduate student in the Department of Cellular and Structural Biology, and Charis Uhlson, a research associate at the University of Colorado Health Sciences Center. Robert Murphy, Ph.D., professor of pharmacology at the University of Colorado Health Sciences Center, is also a co-author.

Many abusers get the drugs from the medicine cabinets of family and friends. ABC4 News talked to two men who are recovering from prescription drug abuse at the Journey Healing Centers.

For one man, nearly two decades of painful addiction started when his father gave him a prescription pain killer for his headache at age 12. "I liked the way it made me feel,” the man, who asked not to be identified, told ABC4 News.

This eventually led to stealing from his parents’ medicine cabinet and later from extended family. "We’d go to grandparents or aunts and uncles and I would start looking in medicine cabinets and finding most people left a lot of their painkillers in the bathrooms," he continued.

Another man said his near-fatal addition started in college after an accident left him with an injured wrist and back. Six months later he was hooked on the prescription painkillers the doctors gave him. "I’d wake up in the morning and feel that I’d have to take two painkillers just to get out of bed," he said.

When ABC4’s Noah Bond asked if anyone noticed that the pills were missing from their medicine cabinets, one man said he would replace whatever he took with a similar-looking pill.

Both men agreed to share their stories in the hopes of educating people to lock up or properly dispose of their prescription medications. "I’d strongly advise to throw them away. There are centers where you can actually take your medications to dispose of it properly," said one man.

The Midvale Police Department is hosting a prescription disposal day at Hillcrest High School April 24, and everyone is welcome to drop off expired or unused medication.

Go to www.medicationdisposal.utah.gov for information about other disposal places. For more information on Journey Healing Centers, call 1-866-535-8958.

To add to the embarrassment, the assistant police chief of Catoosa was arrested recently and preachers, teachers and lawyers have been caught with pills. Police say the problem has escalated to epidemic proportions.

Last year alone, 125 million pain pills were dispensed in Oklahoma. This number is significant given that the population of the entire state is only 3.5 million. Current dispensing rates are enough for 35 pills per every man, woman and child in the state.

The three most abused prescriptions in the Tulsa area include hydrocone, oxycodone and Xanax. Addicts are known to take as many as dozens of pills a day.

In a related story, Officer Joe Gho of the Tulsa Police Deparment said, "I’ve actually interviewed several people who take 100 a day, which is incredible.The first time I heard that, it shocked me. Not anymore. I interview people constantly who tell me the same thing."

The use of painkillers often starts as a very legitimate need, but the tolerance that can build over the course of taking the medication can develop into a full blown addiction. As Gho noted, these are basically good people who get caught up in an addiction and don’t know how to stop it.

What causes the most trouble for addicts is when legal problems start. The addiction begins and they can no longer get their pills legitimately from doctors, hospitals or pharmacies. At that point, they will look for illegal ways to get the pills they need. These individuals risk 20 years in prison because the pull of the addiction is so strong.
 

According to the Canadian Press, the website reported that Dave Watson said in a deposition that he told then-Trojans coach Pete Carroll about his addiction in February 2008, but was allowed to keep his job and use a vehicle provided by USC.

Watson was involved in a car accident in May 2008, in which he pleaded no contest to DUI charges and received three years’ probation, SI.com reported. The driver of the car Watson hit is now suing Watson and USC.

In the three months between Watson’s alleged discussion with Carroll and the crash, Watson was prescribed 1,680 tablets of pain medication, SI.com reported, citing the deposition. Carroll reportedly fired Watson eight months after the accident, saying the defensive line coach was too hard on players.

Watson said under oath that he had developed a significant addiction to painkillers after sustaining a serious knee injury while playing for the University of Minnesota.

Accoring to SI.com, a hearing is scheduled for Jan. 26 in a Los Angeles courtroom to address Carroll’s pending deposition in the civil case.

"I love Aerosmith; I love performing as the lead singer in Aerosmith. I am grateful for all of the support and love I am receiving and am committed to getting things taken care of," the 61-year-old performer said in a statement released Tuesday.

The Associated Press reports that the band canceled a summer tour in August after Tyler fell off the stage during a performance in South Dakota and broke his left shoulder.

Dr. Brian McKeon, who is treating Tyler, said in a statement that orthopedic injuries over the past decade have left the singer with severe chronic pain that will require surgeries on his knees and feet.

Tyler checked into rehab last year to recover from several foot surgeries and physical therapy. He said the procedures were to correct longtime foot injuries resulting from his physical performances.

The singer was known for heavy drug and alcohol abuse in the 1970s and early 1980s, but completed rehabilitation in 1986.

Gregg Zoroya of USA Today writes that the findings show the continued toll on the military from fighting wars in both Iraq and Afghanistan since 2003—wars that have required troops to serve multiple combat deployments.

"We are aware that more prescription drugs are being used today for pain management and behavioral health issues," Brig. Gen. Colleen McGuire, director of the Army Suicide Prevention Task Force, said Wednesday. "These areas of substance abuse along with increased use of alcohol concern us."

The survey showed that pain relievers were the most abused drug in the military, used illicitly at a rate triple that of marijuana or amphetamines, the next most widely abused drugs. About 15% of soldiers said they had abused prescription drugs in the 30 days before they were questioned for the survey. About 10% of Marines said the same thing.

Prescription drug abuse is "an issue for American society as well, and we’re looking at it from every possible angle," McGuire said.

Painkiller abuse among troops has soared since 2005, the last time a similar study was conducted. The 2005 survey showed that 4% of soldiers had abused painkillers in the previous 30 days, compared with 13% in 2008. Abuse within the previous year was 10% in 2005 compared with 22% in 2008.

The authors of the report said different questions were used in 2008 compared with previous years, which makes an exact comparison difficult. The 2008 survey asked more specific questions, such as whether troops were engaged in any non-medical use of the drugs they were prescribed.

Prescription drug abuse among the civilian population dropped in 2008 compared with 2007, a federal report released in September shows.

USA Today reported last year that narcotic pain-relief prescriptions for injured or wounded U.S. troops jumped from 30,000 a month to 50,000 since the Iraq war began.
Lt. Gen. Eric Schoomaker, the Army surgeon general, created a task force this year to review the service’s pain management practices.

In addition, the Army is expanding programs to treat and educate soldiers about drug abuse. But the service struggles to provide enough drug counselors and needs to hire 270 to 300, Gen. Peter Chiarelli, Army vice chief of staff, said last month.

Other survey findings include:

•The percentage of troops showing signs of post-traumatic stress disorder increased during the war years. In a 2005 survey, 7% of the servicemembers described symptoms suggesting PTSD. That increased to 11% in the 2008 study.

The largest increases were within the Army and Marine Corps, the two service branches doing most of the fighting in Iraq and Afghanistan. The rate of soldiers who described problems suggestive of PTSD increased from 9% in 2005 to 13% in 2008, and from 8% to 15% among Marines, the survey results show.

•Nearly 60% of Marines admit engaging in binge drinking. The rate of heavy alcohol use — defined as five or more drinks per occasion once a week—among all servicemembers ages 18 to 35 remained higher than in the civilian population.

•Servicemembers admitting that they had thoughts of suicide during the year prior to being surveyed doubled from 1% in 2005 to 2% in 2008.
 

"At that point, he was, uh, he [Tiger Woods] was snoring," Adams told the police. "He was snoring?" asked the investigator. "He was actually snoring," Adams confirmed.

Gerald Posner writes for the Daily Beast that he learned from trauma doctors that Woods should have been hyper-alert because of the adrenaline rush naturally associated with an accident such as his.

One law enforcement officer familiar with the investigation told the Daily Beast that police on the scene suspected that Woods was disoriented and loopy because he had taken Ambien, a prescription sleeping pill. A person familiar with Woods’ medical treatment two years ago told Posner that Woods has used prescription sedatives, when injured, to help him sleep.

Despite this, the Florida Highway Patrol did not administer any drug or alcohol tests to Woods, telling the Orlando Sentinel that it did not have the “probable cause” for such tests.

But the incident raises questions about Woods and his pill habits. The suggestion of an Ambien link to the early-morning crash comes on the heels of reports that one of Woods’ alleged mistresses told friends that she and Woods liked to have “crazy” sex in an “Ambien haze.”

Meanwhile, a source familiar with Tiger’s medical treatment in the latter half of 2007 told Posner that Woods’ regular dosing of painkillers was “potentially a problem” during those six months because of the addictive nature of his medications. That coincides with Woods tearing his left knee ACL, a common athletic injury, in July 2007. Woods and his advisers decided against surgery then and instead he continued playing and winning on the PGA Tour.

Posner asked Woods’ agent, Mark Steinberg, about the golf star’s prescription drug history. His response came by email on Friday: “As any doctor would attest, patients are universally prescribed medication for bone fractures and following major orthopedic surgery. Tiger’s care has been managed with especially attentive observation by leading medical professionals, and others simply aren’t in a responsible position to make any assessments. Most importantly, the specifics of his medical care ought to be private, which is why unending Internet innuendo about his condition is so irresponsible and offensive. For amateurs to make speculative judgments about the quantity, propriety, or duration of a patient’s care is reprehensible.”

Posner notes that in some ways this answer sounded similar to part of the statement that was first issued under Woods’ name after the car accident: "This is a private matter, and I want to keep it that way. Although I understand there is curiosity, the many false, unfounded, and malicious rumors that are currently circulating about my family and me are irresponsible.”

Speaking at a meeting of the American Association for Cancer Research in Boston, the scientists also claim to have found a drug that counters this effect.

Dr. Patrick Singleton, assistant professor of medicine at the University of Chicago Medical Center and principal author of the research, told the meeting of experts that in laboratory tests, morphine not only strengthened blood vessels but also appeared to make it easier for cancers to invade other tissues and spread.

But he said this could be overcome by a drug called methylnaltrexone or MNTX, which was developed in the 1980s to prevent morphine-related constipation but was only recently approved in the US. It appears to work without interfering with the pain-relieving properties of the opiate.

In mice with lung cancer, MNTX inhibited the apparent tumor-promoting effects of opiates, and reduced the spread of cancer in the mice by 90 percent.

"If confirmed clinically, this could change how we do surgical anesthesia for our cancer patients," said Dr. Singleton. "It also suggests potential new applications for this novel class of drugs which should be explored."

The tests were started after his colleague, anesthetist Jonathan Moss, noted that several patients receiving this kind of opiate blocker survived longer than might be expected after surgery.

Dr. Laura Bell of Cancer Research UK said morphine has a long history of providing effective pain relief, and that more tests were needed before making any changes in treatment.

"Research in this area is in the early stages, so it’s too early to tell whether opiate-based painkillers have an effect on cancer growth. Much more research would be needed to justify changing the way opiates are used to treat people with cancer."

By 2001, that number had doubled to 8.4 million nonmedical pain reliever users annually. In 2006 Birnbaum et al. studied the healthcare costs associated with the abuse of pain relievers (opioids: RxO).

In 2001 there were approximately 50,000 individuals admitted for treatment of RxO abuse, according to information from Treatment Episode Data Sets (TEDS). The researchers examined both treatment costs and excess costs. Treatment costs are related to treatment for the RxO abuse, while excess costs are medical costs other than treatment that are related to RxO abuse.

The researchers calculated treatment costs using publicly available information about spending for substance abuse treatment at federal, state and private levels. To examine the excess costs, the study examined records from a large private insurance database to look at the non-treatment costs of RxO abusers compared to other insured individuals. They also used publicly available information about Medicaid and uninsured costs for RxO abusers.

The total cost of healthcare for RxO treatment was estimated to be $2.6 billion, with over $126 million just in 2001. 64% of these costs were covered by public funds. Excess medical costs related to RxO abuse were over $2.4 billion, with 66% covered by public funds.

There were limitations with the study. Clinician reporting bias may have affected the information obtained from the TEDS. Recent attention given to RxO abuse may have influenced how often admissions were designated to be RxO abuse-related. Also, because the information was obtained for patients seeking treatment at state licensed treatment centers, it might not be representative of the general population.

Although the study shows limitations, it is important to recognize the cost of RxO abuse in the United States. More people have access to RxOs than ever before and are taking them without adequate supervision of a healthcare provider. It is critical that RxOs be available to those suffering chronic pain, but more attention is needed for those taking RxOs. Education and early intervention of those misusing medication is important if healthcare costs are going to reflect an improvement.