Category: Opium

 More and more Americans with chronic pain not caused by cancer are taking medically prescribed opioids like Oxycontin (oxycodone) and Vicodin (hydrocodone). The January 19 Annals of Internal Medicine features the first study to explore the risk of overdose in patients prescribed opioids for chronic noncancer pain in general health care. The study links risk of fatal and nonfatal opioid overdose to prescription use — strongly associating the risk with the prescribed dose.

A team led by Michael Von Korff, ScD, a senior investigator at Group Health Research Institute, studied nearly 10,000 patients who received multiple opioid prescriptions for common chronic pain conditions like back pain and osteoarthritis. Patients who received higher opioid doses were 9 times more likely to overdose than were those receiving low doses. Still, most of the overdoses occurred among patients receiving low to medium doses, because prescriptions at those levels were much more common.

More than 8 million U.S. adults — 3 percent of all of them — are estimated to be using opioids long-term for chronic pain. The Centers for Disease Control and Prevention (CDC) recently reported that nearly 14,000 U.S. deaths involved prescription opioids in 2006, more than triple the number in 1999. Between 1999 and 2006, nearly 65,000 drug overdose deaths in the United States were reported to involve opioid analgesics.

"Some studies have indicated that fatal opioid overdoses occur most often among people abusing prescription drugs or obtaining them from non-medical sources," Dr. Von Korff said. "But our results suggest that many overdoses may occur among people using prescribed opioids."

Dr. Von Korff said that this research and the data reviewed cannot determine whether higher doses are a cause of overdose, but he noted that physicians should carefully evaluate and closely monitor patients using opioids long-term.

Previous research had not tracked nonfatal overdoses. "Fatal overdose may be only the tip of the iceberg," said Dr. Von Korff. "For every fatal overdose in our study, 7 nonfatal overdoses occurred, and most of the nonfatal overdoses were medically serious."

"Our findings are concerning and need to be studied in larger populations," said the study's first author, Kate M. Dunn, PhD, senior lecturer in epidemiology at the Arthritis Research Campaign National Primary Care Centre at Keele University in the U.K.

Opioid overdose occurred at similar rates across all ages. The overdose events identified were not directly evaluated to assess all potential contributing factors, such as suicide attempts, opioids obtained from nonmedical sources, or accidental or intentional ingestion of more opioid than prescribed. Although suicide attempts and drug abuse were noted in only a minority of the overdoses in this study, opioid overdoses appeared to occur more often among patients with a history of depression or substance abuse, Dr. Dunn said. Depression tends to be common among chronic pain patients using opioids long-term.

"Nationwide, opioids are widely prescribed long-term for many patients with chronic non-cancer pain," said coauthor Bruce M. Psaty, MD, PhD, a senior investigator at Group Health Research Institute and a professor of medicine, epidemiology, and health services at the University of Washington, where he co-directs the Cardiovascular Health Research Unit. "So a significant opportunity exists to improve safety and the risk-benefit profile through more careful and cautious prescribing."

Opioids include not only opiates, which come from the opium poppy, he explained — but also similar synthesized chemicals.

A three-year grant from the National Institute on Drug Abuse, part of the National Institutes of Health, funded the CONSORT (CONsortium to Study Opioid Risks and Trends) study. The Wellcome Trust supported Dr. Dunn's participation.

Other coauthors were Senior Investigator Carolyn M. Rutter, PhD, and Analyst/Programmer Kathleen W. Saunders, JD, of Group Health Research Institute; Caleb J. Banta-Green, MSW, MPH, PhD, Joseph O. Merrill, MD, MPH, and Mark D. Sullivan, MD, PhD, of the University of Washington; Michael J. Silverberg, PhD, MPH, and Cynthia I. Campbell, PhD, of Northern California Kaiser Permanente in Oakland; and Constance M. Weisner, DrPH, MSW, of Northern California Kaiser Permanente in Oakland and the University of California, San Francisco.

Pathological gambling can be successfully treated with medications that decrease urges and increase inhibitions, according to researchers at the annual meeting of the American College of Neuropsychopharmacology (ACNP). Researchers found positive outcomes in gamblers treated with medications often used for substance addictions.

People with pathological gambling disorder will continue their gambling behavior in the face of damaging consequences to themselves and their families. Dr. Jon Grant and his team at the University of Minnesota used tasks that measure cognition to identify what motivates this extreme type of gambling behavior. They enrolled men and women with a primary diagnosis of pathological gambling in one of three medication studies. Study sites varied in size from 70 to 100 participants.

Researchers sought to understand how gamblers decide whether or not to bet by focusing on two brain processes: urge and inhibition. In order to group individuals into categories that address differences in their biology, Grant separated pathological gamblers into two major subtypes: gamblers who are driven by urge (i.e., individuals who report gambling when the desire becomes too strong to control), and those who do not show normal inhibition of impulsive behaviors (i.e., individuals who report being unable to restrict behaviors even when urges are minimal or virtually non-existent).

In the first subtype, gamblers who are driven by urge responded well to treatment with medications that block the brain opioid system (e.g., naltrexone) or certain receptors for the neurotransmitter glutamate (e.g., memantine). Grant also found that family history plays an important role in refining this group even further. People with a family history of addiction responded even better to the opioid blocker, which has been shown in other studies to decrease the urge to use substances such as alcohol.

The second subtype, gamblers who have difficulty inhibiting their behaviors and react to the smallest desires, respond well to medications that act on a specific enzyme, catechol-O-methyl-transferase (COMT), which plays a major role in the function of the prefrontal cortex. Researchers found that decreasing the function of COMT can increase one's ability to inhibit their desire to gamble.

"By understanding these different subtypes, we are able to target the core biology of the illness with individualized treatment," said Jon Grant, MD, JD, MPH, Associate Professor of Psychiatry at the University of Minnesota and ACNP member. "When we look at pathological gambling as an addiction and try to understand the sense of urges and inhibitions, we are able to target the treatment with medication more effectively."

Grant cautioned that while these results are exciting and a majority of people respond to these medications, there are still some for whom these medications do not work. Additional research is needed to further refine the subtypes.

Pathological gambling affects approximately one to two percent of the population. Currently available treatments are associated with extremely high relapse rates.

cientists are adding additional brush strokes to the revolutionary new image now emerging for star-shaped cells called astrocytes in the brain and spinal cord. Their report, which suggests a key role for astrocytes in morphine's ability to relieve pain and cause addiction, appears online in ACS' Journal of Proteome Research, a monthly publication.

In the study, Piotr Suder and colleagues point out that nearly everyone viewed astrocytes — the most abundant cells in the brain — as supporting actors in the drama of brain activity. Scientists thought astrocytes simply propped up neurons, nerve cells that transmit signals, and kept them in proper position. Studies during the last several years, however, suggest that these cells are just as their Greek name suggests — stars.

The scientists added morphine to a group of astrocytes in cell culture for several days. They found that the morphine-exposed cells showed increased levels of nine proteins that appear to play a role in maintaining the normal function of nerve cells.

"These proteins, after additional detailed study of their function, may serve as a potential marker of drug addiction, or may be the targets for potential therapy," the article notes.

Journal Reference:

1. Piotr Suder, Anna Bodzon-Kulakowska, Pawel Mak, Anna Bierczynska-Krzysik, Michal Daszykowski, Beata Walczak, Gert Lubec, Jolanta H. Kotlinska, Jerzy Silberring. The Proteomic Analysis of Primary Cortical Astrocyte Cell Culture after Morphine Administration. Journal of Proteome Research, 2009; 8 (10): 4633-4640 DOI: 10.1021/pr900443

 Deaths from opioid use in Ontario, Canada, have doubled since 1991 and the addition of long-acting oxycodone to the drug formulary was associated with a 5-fold increase in oxycodone-related deaths, found a new study in CMAJ (Canadian Medical Association Journal). Most of these additional deaths were accidental.

Opioids are among the most commonly prescribed medications in Canada and are often used for patients with chronic non-malignant pain. Other studies have argued that prescribing is not a major contributor to the adverse health effects of opioid abuse, yet this study suggests that increased rates of opioid prescriptions are a significant factor in accidental opioid-related deaths.

The study looked at prescribing data from 1991 to 2007 from IMS Health Canada, which collects information from almost two-thirds of Canadian pharmacies, and deaths attributed to opioid use from records of the Office of the Chief Coroner of Ontario between 1991 and 2004. It also linked the coroner's data to health care databases to track patients' medical visits.

Prescriptions for opioid pain medications increased by 29%, with codeine the most frequently prescribed, although the number of prescriptions for that drug declined during the study period. Oxycodone prescriptions rose more than 850%, much more rapidly than any other opioid, and accounted for 32% of the almost 7.2 million prescriptions for opioids dispensed in 2006.

Between 1991 and 2004, 7099 deaths with complete records were attributed to alcohol and/or drugs. In 3406 of these deaths — 61.9% — opioids were implicated as cause of death. The median age of death was 40 years and 67% were men. Suicide was a factor in 23.6% of deaths.

"The rise in opioid-related deaths was due in large part to inadvertent toxicity," write Dr. Irfan Dhalla, of the University of Toronto and coauthors. "There was no significant increase in the number of deaths from suicide involving opioids over the study period."

After linking the coroner's data to health care databases, the researchers included 3066 deaths. Many (66.4%) of these patients had seen a physician at least once in the 4 weeks preceding their death, with diagnosis of mental health problems and pain-related complaints the most common reasons for medical attention.

"The societal burden of opioid-related mortality and morbidity in Canada is substantial," write the authors. "In our study, the annual incidence of opioid-related deaths in 2004 (27.2 million) falls between the incidence of death from HIV infection (12 per million) and sepsis (40 per million)."

They conclude that the frequency of visits to physicians and opioid prescriptions in the month before death suggest a missed opportunity for prevention.

In a related commentary, Dr. Benedikt Fischer of Simon Fraser University and coauthor write "the pre-eminent risk in most deaths was from the use of multiple drugs involving prescription opioids and other substances that are widely and legally dispensed. As prescription drugs are involved in more overdose deaths than either heroin or cocaine in North America, the profile of the people who are dying may be changing from marginalized people to more "middle class."

The authors argue that governments must lead in developing a preventative strategy for this different demographic and refocus the federal drug policy that currently targets marginalized people.

Journal References:

1. Irfan A. Dhalla, Muhammad M. Mamdani, Marco L.A. Sivilotti, Alex Kopp, Omar Qureshi, David N. Juurlink. Prescribing of opioid analgesics and related mortality before and after the introduction of long-acting oxycodone. Canadian Medical Association Journal, 2009; 181 (12): 891 DOI: 10.1503/cmaj.090784

Although morphine has been the gold-standard treatment for postoperative and chronic cancer pain for two centuries, a growing body of evidence is showing that opiate-based painkillers can stimulate the growth and spread of cancer cells. Two new studies advance that argument and demonstrate how shielding lung cancer cells from opiates reduces cell proliferation, invasion and migration in both cell-culture and mouse models.

The reports–to be presented November 18, 2009, at "Molecular Targets and Cancer Therapeutics," a joint meeting in Boston of the American Association for Cancer Research, the National Cancer Institute, and the European Organization for Research and Treatment of Cancer–highlight the mu opiate receptor, where morphine works, as a potential therapeutic target.

"If confirmed clinically, this could change how we do surgical anesthesia for our cancer patients," said Patrick A. Singleton, PhD, assistant professor of medicine at the University of Chicago Medical Center and principal author of both studies. "It also suggests potential new applications for this novel class of drugs which should be explored."

The proposition that opiates influence cancer recurrence, prompted by several unrelated clinical and laboratory studies, has gradually gained support. It started with a 2002 palliative-care trial in which patients who received spinal rather than systemic pain relief survived longer. Soon after that, Singleton's colleague, anesthesiologist Jonathan Moss, noticed that several cancer patients receiving a selective opiate blocker in a compassionate-use protocol lived longer than expected. Two recent retrospective studies found that breast and prostate cancer patients who received regional rather than general anesthesia had fewer recurrences. In February, 2009, the Anesthesia Patient Safety Foundation highlighted the issue.

Moss's palliative-care patients were taking methylnaltrexone (MNTX), developed in the 1980s for opiate-induced constipation by the late University of Chicago pharmacologist Leon Goldberg. Goldberg modified an established drug that blocks morphine so that it could no longer cross the protective barrier that surrounds the brain. So MNTX blocks morphine's peripheral side effects but does not interfere with its effect on pain, which is centered in the brain. It won FDA approval in 2008.

"These were patients with advanced cancer and a life expectancy of one to two months," Moss recalled, "yet several lived for another five or six. It made us wonder whether this was just a consequence of better GI function or could there possibly be an effect on the tumors."

So Singleton, Moss and colleagues, including Joe G.N. Garcia, MD, professor of medicine at the University of Chicago, began a series of studies looking at the many peripheral effects of opiates and the potential benefits of blocking those effects.

In laboratory studies, morphine can directly boost tumor-cell proliferation and inhibit the immune response. The researchers found that opiates also promote angiogenesis, the growth of new blood vessels, and decrease barrier function–effects that may exacerbate diseases involving vascular leakiness including acute lung injury in experimental models. In a surgical setting, decreased barrier function may make it easier for tumors to invade tissue and spread to distant sites. Increased angiogenesis helps cancers thrive in a new site.

In the studies to be presented Nov. 18, Singleton and colleagues focus on the mu opiate receptor as a regulator of tumor growth and metastasis and examine the ability of methylnaltrexone to attenuate these effects.

Using two different models of non-small cell lung cancer, the research teams showed that MNTX inhibited the tumor-promoting effects of opiates. In one study, using bronchioloalveolar carcinoma cells, MNTX blocked oncogenic signaling and prevented tumor-cell proliferation and migration.

In the other study, using Lewis lung carcinoma cells, mice without the mu opiate receptor did not develop the tumors that normal mice did when injected with cancer cells. The researchers further showed that MNTX reduced proliferation of cancer cells by 90 percent in normal mice. It also prevented invasion in cell culture and tumor growth and metastasis in mice.

The opioid receptor promotes Lewis lung cancer tumor growth, angiogenesis and metastasis, the authors conclude in a summary of the second study. "Methylnaltrexone attenuates these oncogenic effects."

"In conjunction with previous studies on opiate-induced angiogenesis by our laboratory and others, these experimental data suggest a plausible explanation for the epidemiologic observations," notes Moss, professor of anesthesiology and critical care at the University of Chicago. "If these laboratory studies are confirmed clinically, the selection of anesthetic technique used during the operative procedure and the possible use of opiate antagonists in the perioperative period may be important."

Additional contributors to the project include Frances Lennon, PhD, Biji Mathew, PhD, and Ravi Salgia, MD, all of the University of Chicago.

 Stress-evoked changes in circuits that regulate serotonin in certain parts of the brain can precipitate a low mood and a relapse in cocaine-seeking, based on mouse studies published online this week in the Proceedings of the National Academy of Sciences.

"The impetus for this research was our interest in how stress alters the brain's cell receptors and protein signals in ways that lead to mood changes, depression, anxiety, and drug seeking," said Dr. Michael Bruchas, acting instructor of pharmacology at the University of Washington (UW), who with Dr. Benjamin Land, a former UW doctoral student now in the Department of Psychiatry at Yale University, co-led the recent study of the adverse effects of stress-activated brain pathways. The senior author was Dr. Charles Chavkin, the Allan and Phyllis Treuer Professor of Pharmacology and director of the UW Center for Drug Addiction Research

A common belief is that drug seeking is regulated by dopamine, a chemical nerve signal associated with motivating and rewarding behavior. Dopamine may still have a key role, the researchers noted, which is why they were surprised to find harmful effects of stress converging in a brain region- the dorsal raphe nucleus –where nerve cells that use serotonin are abundant. These nerve cells also project to other structures found on either side of the brain — the nucleus accumbens — which are thought to play roles in feeding and drug addiction. Serotonin is a chemical nerve signal that has been associated with wake and sleep cycles, mood, anger, status and aggression

In explaining their study, the researchers said that the dynorphin/kappa opioid system, found in certain brain cells, can be activated either through repeated stress or by giving a chemical that triggers a receptor on the cells. Activation of this system produces what is called conditioned place aversion in mice. They avoid smells, locations or tactile sensations similar to those present during a troubling experience. Research suggests that this response is mediated by the stress-evoked release of dynorphins, the "feel bad" brain signals.

For mice, meeting a dominant male mouse is disheartening. Dr. Land likened the stressfulness of this situation to sitting in a classroom with the schoolyard bully. Facing an aggressor, mice will admit social defeat by raising their paws in an "I give up" pose. If the lab mice have received cocaine before and are abstaining now, they will want the drug again.

"Stress appears to be a motivator for the relapse in drug seeking," Land said, "They feel crummy so they go where there might be something that will make them feel okay again." They head to a spot that had the drug available in the past, an action researchers call cocaine place preference.

Scientists had previously proposed that an activated dynorphin/kappa opioid receptor system stopped the release of dopamine and thereby made the mice feel miserable enough to cause aversions. However, even mice bred to be dopamine-deficient still responded with aversions. When scientists inactivated the kappa opioid receptors involved in the serotonin system in the dorsal raphe nucleus — the serotonin-abundant region of the brain — they were able to block both the aversive responses and the stress-induced reinstatement of cocaine-place preference.

Mice that had their kappa opioid receptors genetically "knocked out" did not develop aversive responses to chemical triggers. After the scientists genetically restored these missing receptors in the dorsal raphe nucleus of the brain, the mice responded to the trigger with place aversion. However, the researchers found that genetically installed, mutated receptors that can't activate a brain protein called p38 MAPK couldn't provoke aversive responses.

The researchers concluded that activation of the kappa opioid receptor, either pharmacologically or by stress-evoked release of dynorphins, may regulate a serotonin system through projections from the dorsal raphe nucleus of the brain to other parts of the brain, the nucleus accumbens. Theirs is one of the first investigations into sources of the serotonin system projections and how this connection is regulated by stress-evoked mediators. This pathway — induced by dynophins released during stress — might re-ignite extinguished drug-seeking behaviors by weakening the serotonin tone of the nucleus accumbens.

These findings, Bruchas said, are only a first, foundational step. Still to be discovered are: What are the activities of the kappa opioid receptor? Is it decreasing serotonin levels? Is it lowering the firing rates of nerve cells?

The researchers expressed hope that future work on how this pathway functions may provide more insight into the brain mechanisms linking stress, depression, and addiction.

When asked if it would be possible to intervene in this pathway, the researchers answered that work is under way by other groups on the kappa opioid receptor system as a possible target for treating depression.

In addition to Land, Bruchas and Chavkin, researchers on the study were Selena Schattauer, William J. Giardino, Megumi Aita, and Daniel Messinger, all of the UW Department of Pharmacology; and Thomas S. Hnasko and Richard Palmiter, both of the UW Department of Biochemistry. Palmiter is also a Howard Hughes Medical Institute investigator.

The research was supported by U.S. Public Health Services grants from the National Institute on Drug Abuse of the National Institutes of Health, and the Hope for Depression Foundation.

 Scientists at Georgia State University have uncovered the mechanisms of how pain in infancy alters how the brain processes pain in adulthood.

Research is now indicating that infants who spent time in the neonatal intensive care unit (NICU) show altered pain sensitivity in adolescence. These results have profound implications and highlight the need for pre-emptive and post-operative pain medicine for newborn infants.

The study, published online in the journal Frontiers in Behavioral Neuroscience, sheds light on how the mechanisms of pain are altered after infant injury in a region of the brain called the periaqueductal gray, which is involved in the perception of pain.

Using Sprague-Dawley rats, Jamie LaPrairie, a graduate student in associate professor Anne Murphy's laboratory, examined why the brief experience of pain at the time of birth permanently decreased pain sensitivity in adulthood.

Endogenous opioid peptides, such as beta-endorphin and enkephalin, function to inhibit pain. They're also the 'feel good' substances that are released following high levels of exercise or love. Since these peptides are released following injury and act like morphine to dampen the experience of pain, LaPrairie and Murphy tested to see if the rats, who were injured at birth, had unusually high levels of endogenous opioids in adulthood.

To test this hypothesis, LaPrairie and Murphy gave adult animals that were injured at the time of birth a drug called naloxone. This drug blocks the actions of endogenous opioids. After animals received an injection of naloxone, they behaved just like an uninjured animal.

The scientists then focused on the periaqueductal gray region to see if inflammation at birth altered the natural opioid protein expression in this brain region. Using a variety of anatomical techniques, the investigators showed that animals that were injured at birth had endogenous opioid levels that were two times higher than normal.

While it's beneficial to decrease pain sensitivity in some cases, it's not good to be completely resilient to pain.

"Pain is a warning sign that something is wrong," Murphy explained. "For example, if your hand is in water that's too hot, pain warns you to remove it before tissue damage occurs."

Interestingly, while there is an increase in endorphin and enkephalin proteins in adults, there is also a big decrease in the availability of mu and delta opioid receptors. These receptors are necessary in order for pain medications, such as morphine, to work. This means that it takes more pain-relieving medications in order to provide relief as there are fewer available receptors in the brain. Studies in humans are reporting the same phenomenon.

The number of invasive procedures an infant experienced in the NICU is negatively correlated with how responsive the child is to morphine later in life; the more painful procedures an infant experienced, the less effective morphine is in alleviating pain.

The study by LaPrairie and Murphy has major implications for the treatment of infants in neonatal intensive care. On average, a prematurely born infant in a neonatal intensive care unit will experience 14 to 21 invasive procedures a day, including heel lance, insertion of intravenous lines, and intubation. All of these procedures are quite painful and are routinely conducted without prior analgesics or anesthetics.

"It's imperative that pain be treated," Murphy said. "We once assumed that a newborn infant is insensitive to pain, and this is clearly not the case. Even at that period of time, the central nervous system is able to respond to pain, and our studies show that the experience of pain completely changes the wiring of the brain in adulthood."

The next steps in Murphy's research include the study of how neonatal injury at birth alters stress responses, as well as the affects of infant injury on long-term learning and memory.

LaPrairie's and Murphy's work was supported by the National Institutes of Health, the Center for Behavioral neuroscience, a consortium of seven universities at Georgia State, and the Georgia State Brains and Behavior Program.

The article, titled "Neonatal injury alters adult pain sensitivity by increasing opioid tone in the periaqueductal gray," appears in the September 2009 edition of journal Frontiers in Behavioral Neuroscience, Vol. 3, p. 1-11.

Almost a quarter of a million individuals addicted to heroin are incarcerated in the United States each year. However, many prison systems across the country still do not offer medical treatment for heroin and opiate addiction, despite the demonstrated social, medical and economic benefits of opiate replacement therapy (ORT).

According to new research from The Miriam Hospital, Brown University and their affiliated Center for Prisoner Health and Human Rights, just half of all federal and state prison systems offer ORT with the medications methadone and buprenorphine, and only in very limited circumstances. Similarly, only twenty-three states provide referrals for some inmates to treatment upon release from prison. These policies are counter to guidelines issued by both the World Health Organization (WHO) and the Centers for Disease Control and Prevention, which say prisoners should be offered ORT for treatment of opiate dependence.

The study's findings are published online by Drug and Alcohol Dependence.

"Pharmacological treatment of opiate dependence is a proven intervention, is cost-effective and reduces drug-related disease and reincarceration rates, yet it remains underutilized in U.S. prison systems," said Amy Nunn, ScD, the study's lead author and an assistant professor of medicine (research) at The Warren Alpert Medical School of Brown University. "Improving correctional policies for addiction treatment could dramatically improve prisoner and community health as well as reduce both taxpayer burden and reincarceration rates."

"Opiate addiction, like all forms of addiction, causes long-term changes to the structure and functioning of the brain, which is why it is classified as a disease. Addiction requires treatment just as other chronic diseases, like diabetes and cancer, do. Unfortunately, there is a large gap between the number of prisoners who require addiction treatment and those who actually receive it," added senior author Josiah Rich, MD, MPH, co-director of the Center for Prisoner Health and Human Rights at The Miriam Hospital and Alpert Medical School.

The U.S. has the world's highest incarceration rate, with approximately 10 million individuals incarcerated each year. More than half of inmates have a history of substance use and more than 200,000 people with heroin addiction are incarcerated annually. Inmates face disproportionately higher burdens of mental illness, substance use and infectious diseases, including HIV/AIDS. Meanwhile, their transition back to their communities is often associated with increased sexual health and drug-related risks, and more than half will relapse within one month of their release.

For the past four decades, methadone has been the treatment of choice for opiate dependence. It prevents withdrawal symptoms and drug cravings, blocks the euphoric effects of other opiates, and reduces the risk of relapse, infectious disease transmission and overdose death. The drug buprenorphine is a newer treatment for opiate replacement that has less likelihood of overdose and is associated with less social stigma. Like methadone, it prevents withdrawal symptoms when an individual stops taking opioid drugs by producing similar effects. Both methadone and buprenorphine are included in WHO's "Essential Medicines" list of drugs that should be made available at all times by health systems to patients.

The Miriam/Brown research team surveyed the medical directors at the 50 state departments of corrections, along with the Federal Bureau of Prisons and the District of Columbia prison, about their facilities' ORT prescribing policies and referral programs for inmates leaving prison. They received a total of 51 of 52 responses.

Although it appears methadone is offered more frequently that buprenorphine, only 28 facilities (55 percent) offer it under any circumstances, although more than half of these provide it only to pregnant women or for chronic pain management. Approximately 45 percent of facilities provided some community linkage to methadone treatment post-release. Meanwhile, only seven prison systems (14 percent) offer buprenorphine in some circumstances, while 15 facilities (29 percent) offer referrals for some inmates to community buprenorphine providers upon release.

When asked why these treatments are not available in their prison system, the majority of facilities indicated they prefer drug-free detoxification over ORT. A number of prison systems also cited security concerns about providing methadone and buprenorphine to inmates. Interestingly, 27 percent of medical directors said they did not know how beneficial methadone is for treating inmates with opiate addiction, while half were unaware of the benefits of buprenorphine.

A major barrier to providing ORT after incarceration appears to be the lack of partnerships with community ORT providers. Many providers also cited their focus on inmate health during incarceration, rather than upon release, as another reason for not linking inmates to ORT after they've been released.

"In spite of overwhelming scientific evidence demonstrating that pharmacological treatment for addiction has greater health and social benefits than abstinence-only policies, many prison directors are philosophically opposed to treating substance use. Most prisons also do not provide referrals for substance use treatment for prisoners upon release," said Nunn. "These trends contribute to high reincarceration rates and have detrimental impacts on community health. Our interviews with prison medical directors suggest that changing these policies may require an enormous cultural shift within correctional systems."

The study was supported by grants from the National Institute of Health's National Institute on Drug Abuse (NIDA/NIH) and Center for AIDS Research (CFAR); and the Tufts Nutrition Collaborative. In addition to Nunn and Rich, co-authors include Nickolas Zeller and Ank Nijhawan from both The Miriam Hospital and Alpert Medical School; Samuel Dickman from Brown University; and Catherine Trimbur from the University of Rochester School of Medicine and Dentistry.

UCLA psychologists have determined for the first time that a gene linked with physical pain sensitivity is associated with social pain sensitivity as well.

Their study indicates that variation in the mu-opioid receptor gene (OPRM1), often associated with physical pain, is related to how much social pain a person feels in response to social rejection. People with a rare form of the gene are more sensitive to rejection and experience more brain evidence of distress in response to rejection than those with the more common form.

The research was published Aug. 14 in the early online edition of Proceedings of the National Academy of Sciences and will appear in the print version in the coming weeks.

The findings give weight to the common notion that rejection "hurts" by showing that a gene regulating the body's most potent painkillers — mu-opioids — is involved in socially painful experiences too, said study co-author Naomi Eisenberger, UCLA assistant professor of psychology and director of UCLA's Social and Affective Neuroscience Laboratory.

In the study, researchers collected saliva samples from 122 participants to assess which form of the OPRM1 gene they had and then measured sensitivity to rejection in two ways. First, participants completed a survey that measured their self-reported sensitivity to rejection. They were asked, for example, how much they agreed or disagreed with statements like "I am very sensitive to any signs that a person might not want to talk to me."

Next, a subset of this group, 31 participants, was studied using functional magnetic resonance imaging (fMRI) at UCLA's Ahmanson–Lovelace Brain Mapping Center during a virtual ball-tossing game in which participants were ultimately socially excluded. Subjects were told that they would be connected over the Internet with two other players who were also in fMRI scanners and that they would all be playing the interactive ball-tossing game. In reality, however, participants were playing with a preset computer program, not other people.

Initially, participants were included in the activity but were then excluded when the two other "players" stopped throwing the ball to them.

"What we found is that individuals with the rare form of the OPRM1 gene, who were shown in previous work to be more sensitive to physical pain, also reported higher levels of rejection sensitivity and showed greater activity in social pain–related regions of the brain — the dorsal anterior cingulate cortex and anterior insula — in response to being excluded," Eisenberger said.

The dorsal anterior cingulate cortex and anterior insula are brain regions often associated with the distress of physical pain. Previous research by Eisenberger and her colleagues has shown that these brain regions are also involved in the pain of social rejection.

"Although it has long been suggested that mu-opioids play a role in social pain — and there are convincing animal models that show this — this is the first human study to link this mu-opioid receptor gene with social sensitivity in response to rejection," Eisenberger said.

"These findings suggest that the feeling of being given the cold shoulder by a romantic interest or not being picked for a schoolyard game of basketball may arise from the same circuits that are quieted by morphine," said Baldwin Way, a UCLA postdoctoral scholar and the lead author on the paper.

Eisenberger argues that this overlap in the neurobiology of physical and social pain makes good sense.

"Because social connection is so important, feeling literally hurt by not having social connections may be an adaptive way to make sure we keep them," she said. "Over the course of evolution, the social attachment system, which ensures social connection, may have actually borrowed some of the mechanisms of the pain system to maintain social connections."

Shelley E. Taylor, UCLA distinguished professor of psychology, is also a co-author on the paper.

The research was funded by a National Institute of Mental Health (NIMH) postdoctoral fellowship, the National Institute on Aging, the NIMH and the Harry Frank Guggenheim Foundation.

NewsPsychology (Aug. 22, 2009) — Pain therapy for cancer patients – whether inpatient or outpatient – is often inadequate. At Heidelberg University Hospital, the use of an innovative electronic system – combined with guidance by an experienced clinical pharmacist – has been successfully tested. The treatment of the patients showed little variance from international guidelines on pain therapy. In addition, patients reported having less pain.

The results of the study have been published in the journal Pain.

The electronic pain relief guide AiDPainCare is an additional instrument of the electronic pharmaceutical guide AiDKlinik, which guides physicians safely through the current pharmaceutical market in Germany with over 64,000 products and successfully helps avoid false dosages, side effects, dangerous drug interaction, and duplications in prescriptions. The medication prescribed by the physician can be transferred from AiDKlinik directly to a prescription or medical report. The system is currently in use in 10 hospitals in Germany and can also be subscribed to by physicians in private practice (http://www.doctors-aid.de).

New consulting module for the electronic pharmaceutical guide AiDKlinik

AiDKlinik was developed in 2003 by the Department of Internal Medicine VI, Clinical Pharmacology and Pharmacoepidemiology, at Heidelberg University Hospital in conjunction with the hospital pharmacy. The Ministry of Education and Research funded development. Third party funding from the Ferdinand Heinrich Mörsel Foundation was acquired especially for the development of AiDPainCare.

“The safety of drug therapy from prescribing to administering is a central aspect of our work,” explains Professor Walter E. Haefeli, Medical Director, Department of Internal Medicine VI, Clinical Pharmacology and Pharmacoepidemiology. Their cooperation unit Clinical Pharmacy (Director: Dr. Thilo Bertsche), working with the Heidelberg Pain Center under the direction of Professor Hubert J. Bardenheuer, has processed the internationally established treatment guidelines in electronic form. The system was tested and successfully implemented for pain therapy of cancer patients on wards at Heidelberg University Hospital Department of Radio-oncology and Radiation Therapy (Medical Director: Professor Jürgen Debus).

Co-analgesics are not prescribed often enough

In a pilot phase of the study, the researchers determined that in pain treatment begun outside the hospital, underdosing with morphine-based analgesics was common and so-called co-analgesics, e.g. antidepressants or cortisone products, were not used sufficiently. “Co-analgesics in particular can frequently improve pain therapy in patients, but are still being prescribed too rarely,” said Bertsche.

The use of AiDPainCare improved the competent prescribing of such co-analgesics and of opioid (opiate-based) pain medication to treat pain peaks and breakthrough pain. In this area especially, AiDPainCare was used to support physician’s therapy for individual patients. In addition, the module provides quick access to general principles on treatment with opioids and legal information. This should reduce unfounded fears about prescribing a narcotic. Flyers designed especially for patients can also be printed.

Introduction at Heidelberg University Hospital shortly

After successful testing, AiDPainCare will be available on all computers at Heidelberg University Hospital shortly. This should make pain therapy in Heidelberg more effective and better tolerated and reduce patients’ fears of pain in the hospital. Moreover, it is planned to offer the module to external users of AiDKlinik.

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The above story is reprinted (with editorial adaptations by newsPsychology staff) from materials provided by University Hospital Heidelberg.

Journal Reference:

1. T Bertsche, V Askoxylakis, G Habl, F Laidig, J Kaltschmidt, SPW Schmitt, H Ghaderi, A Zabel-du Bois, S Milker-Zabel, J Debus, HJ Bardenheuer, WE Haefeli. Multidisciplinary pain management based on computerized decision support in cancer pain patients. Pain, 2009

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of NewsPsychology or its staff.