Medical Blogs

April 16, 2007

Consumers Should Talk To Their Pharmacists About Pain Reliever Safety Pharmacists Can Answers Questions If Consumers Have Concerns

Each year, millions of consumers use pain relievers to treat everything from back aches to symptoms associated with the common cold. Some estimates place the number as high as 48 million in a given week. But as with all medications, products containing acetaminophen, aspirin or ibuprofen should be used with care. Exceeding the recommended daily dose can jeopardize the consumer's recovery and pose real health problems. Recently, the Food and Drug Administration (FDA) has proposed that the most popular pain relievers carry additional warnings on their labels that overuse may result in stomach bleeding or liver and kidney damage.

"It is important for consumers to remember that products containing acetaminophen and some of these other nonsteroidal anti-inflammatory drugs are safe and effective when used properly," said Past APhA President Dr. Jan Engle. "Pharmacists and other healthcare providers always emphasize to patients that they should know the ingredients in all of their medications, including those they buy over the counter. If a patient is concerned that they might be overmedicating, they should speak with their doctor or pharmacist immediately."

APhA recommends the following for consumers who may be taking a pain reliever regularly:

-- Read the label, Follow the Directions -- Consumers should always know which active ingredients are in the products they are using and follow the recommended dose. Do not exceed the recommended daily dose and do not take the medication for longer than directed.

-- Know Your Medicine, Talk to Your Healthcare Provider -- You should not only know the name of your medication, but the common ingredients as well. A consumer survey commissioned by APhA last year confirmed that only 55% of consumer knew the active ingredients of their prescription medicine. Consumers need to 'know their medicine' - many of the most common prescription and over the counter pain relievers and cold treatments contain similar ingredients, which could result in overmedication. If consumers have questions, they should talk to their pharmacist or doctor.

-- Over the counter pain relievers are safe when used as directed on the label -- When used as directed, over the counter pain relievers are safe. People should not stop taking prescribed pain relievers without first consulting their physician.

-- Talk to your pharmacist about over the counter pain medications. Your pharmacist can help you choose the best product for your condition.

The American Pharmacists Association is dedicated to improving medication use and advancing patient care. Founded in 1852 as the American Pharmaceutical Association, APhA is the first established and largest professional association of pharmacists in the United States. APhA's more than 57,000 members include pharmacists, scientists, student pharmacists, pharmacy technicians, and others interested in advancing the profession.

American Pharmacists Association
http://www.aphanet.com/

Chiropractic Resolutions For A Healthy, Pain-Free Year

Start the new year off right by committing to a healthier lifestyle. A few simple and practical lifestyle changes can make a positive impact on your health and can also prevent you from experiencing a painful injury in the year ahead, according to the American Chiropractic Association (ACA).

The ACA and your local doctor of chiropractic urge you to adopt the following New Year's resolutions for a healthier 2007.

1) I will limit my intake of caffeinated coffee, sodas and teas. The caffeine in these drinks can cause dehydration and can rob the body of essential nutrients. Stick to water, natural juices and other decaffeinated beverages.

2) I will avoid over medicating myself and my family. Many over-the- counter and prescription medications have unknown side effects. Discuss alternative remedies with a doctor of chiropractic.

3) I will not carry a heavy purse or briefcase with its strap over my shoulder, unless I place the strap over my head on the side opposite the bag. Wearing a shoulder strap over one shoulder unevenly places the weight of the bag on one side of the body, potentially causing shoulder and back pain.

4) I will not allow my children to carry backpacks that weigh more than 10 percent of their body weight. Beyond that weight, the backpack can cause the wearer to bend forward in an attempt to support the weight on his or her back, instead of the shoulders.

5) I will not lift heavy objects over my head. These types of movements can strain muscles and affect nerves, causing severe neck, shoulder and arm problems.

6) I will not turn my torso while lifting relatively heavy objects. This rotates the spine and can bring on a "back attack."

7) I will avoid the habit of consistently crossing the same knee over the other. Such a habit can also eventually cause misalignment of the spine.

8) I will try to keep moving while I'm at work. If sedentary for the majority of the work day, it is very important to take periodic stretch breaks. Get up from the desk and take a brief walk, and stretch arms and legs as frequently as possible to avoid postural and spinal stress.

9) I will, when using a shovel - in winter or summer - remember to push rather than lift, whenever possible.

10) I will use luggage with wheels whenever possible. Carrying, lifting and moving a heavy suitcase can ruin a vacation.

For more information on chiropractic care, or to find a chiropractor near you, visit ACA's Web site at: http://www.acatoday.org.

American Chiropractic Association
http://www.acatoday.com/

'Botox' Can Ease Writer's Cramp

Botox"' the popular anti- wrinkle treatment, can also ease writer's cramp, suggests a small study published ahead of print in the Journal of Neurology Neurosurgery and Psychiatry.

Writer's cramp describes the painful involuntary, spasmodic muscle contractions of the fingers, hand, or arm during writing. But it can also occur during other manual tasks.

Some people learn to write with their other hand, but in one in four cases, the condition affects both hands, and the condition is difficult to treat. It affects around three to seven in every 100,000 people.

Relaxation techniques, hypnosis, biofeedback, acupuncture, and 'writing re-education exercises' have all been used, but none of these brings sustained relief. And there is as yet no effective drug treatment.

Forty people with writer's cramp were randomly assigned to a course of injections containing either botulinum toxin (botox) or a dummy substitute in two doses, usually into two muscles, over a period of 12 weeks.

Of the 20 people given botox treatment, 14 (70%) said that their condition had significantly improved, and that they wished to continue treatment. Their improvement was confirmed using validated disability and pain scales.

Only six of the 19 people in the dummy group felt that their condition had improved. One person dropped out of the trial.

One person who received the dummy injection at the first session and botox at the second, also registered an improvement in symptoms.

After a year, half of the trial participants were still receiving botox injections, and were finding them helpful.

Side effects included mild and temporary muscle weakness and pain at the injection site. Symptom relief lasted from three to 18 months, with an average symptom free period of four and a half months.

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Contact: Emma Dickinson
BMJ Specialty Journals

Workers' Compensation Ratings Don't Accurately Predict Disabilities

A study of settlement decisions in workers' compensation claims for low back pain has found almost no relationship between the rating of the disability's severity when the claim was settlement and reported pain and disability 21 months later.

Findings were counterintuitive: Claimants with higher disability ratings, which suggest higher severity and less ability to work, fared better than those with lower ratings.

The study shows that "administrative decisions made at the end of the workers' compensation claim process about the ability of someone to work after back injury has very little predictive validity," said Dr. Norton Hadler, a professor of medicine and microbiology/immunology in the University of North Carolina at Chapel Hill's School of Medicine.

Hadler is a co-author of the paper, which was published in the December issue of the Journal of Pain, with colleagues from St. Louis University and the University of Florida. It was based on administrative records in Missouri of workers' compensation claims for low back pain.

Workers' compensation is an important part of America's health-care system, accounting for 3 percent of an employer's gross income, Hadler said.

"Clearly, the rating schemes for workers' compensation are inconsistent, and that fact is stirring enormous pots across the country," Hadler said. "If the outcomes from Missouri generalize, then there is a need to reform how disability is determined."

Another paradoxical finding showed that white claimants faired no better than blacks, even though previous reviews found that blacks were much less likely than whites to be diagnosed with a herniated disk or to have back surgery, had less money spent on their care and received lower disability ratings and smaller settlements.

"It's one of the more perverse observations in our study," said Hadler. "African-Americans were much less likely to be operated on, but the care that the whites got, even though it looks like more care, because it's surgery and it's more expensive, didn't do anything for them."

For their study, the researchers interviewed 580 black and 892 white workers' compensation claimants an average of 21 months after claim settlement to assess how well they were functioning and to determine the contribution of impairment, race and socioeconomic status to their disability ratings.

Hadler said that workers' compensation claims for low back pain represent only 20 to 30 percent of all claims filed but consume a majority of the workers' compensation budget.

The article concludes that "the pattern of results suggests that race/ethnicity and other sociodemographic factors influence medical decision making and … the outcomes of medical care." Furthermore, the flaws in the system "are not distributed evenly" but "are visited disproportionately" on minorities and persons of lower socioeconomic status.

Study collaborators were Drs. John T. Chibnall and Raymond C. Tait from Saint Louis University School of Medicine and Dr. Elena M. Andresen of the University of Florida. Tait was the study's principal investigator and lead author of the article. It is the fifth article that the quartet have published over the last two years.

University of North Carolina at Chapel Hill
210 Pittsboro St. Campus Box 6210
Chapel Hill, NC 27514
United States
http://www.unc.edu/

December Nursing News And Research Briefs

High Risk Patients Use Both Conventional Medicine and Alternative Therapies for Asthma; Some Alternatives Pose Risk In depth interviews with a group of low income mostly female African Americans, all of whom had severe asthma, revealed that all participants used some form of complementary and alternative medicine (CAM) in combination with conventional medicine. Writing in this month’s issue of the Journal of General Internal Medicine, Johns Hopkins University School Nursing researcher Maureen George, PhD, RN notes that "While most subjects trusted prescription asthma medicine, there was a preference for integration of CAM with conventional asthma treatment. CAM was considered natural, effective and potentially curative."

Among the reasons CAM was chosen as an addition to or substitute for conventional care were beliefs that treatment was "more natural" than manufactured agents; could reduce the need for conventional pharmacologic treatment such as steroids; provided protection from illness or for relief of systems; and offered some hope of a cure. While participants denied substituting CAM for prescription medication, most (63%) also reported they had not adhered to their conventional therapy in the two weeks prior to the interviews or that they had missed doses, some as many as ten or more.

The researchers also found that many participants did not disclose their CAM use to providers. When CAM therapies were preferred but covertly used, patients could be at increased risk for poor clinical outcomes due to drug-CAM interactions; unnecessary delays in seeking appropriate medical attention; and insufficient adherence to the patient’s medical plan leading to an unnecessary intensification of conventional therapies. George and colleagues also determined that some patients were using herbs and over-the-counter products in ways that could be harmful, including ingesting camphor-based or mentholated topical salves, dissolving cough lozenges as many as ten at a time in herbal tea, and taking Echinacea, an herb that could result in a worsening of asthma due to allergic reactions.

Studies Contribute to Better Understanding Pain, Reducing its Physical, Economic Consequences--Faculty member Fannie Gaston-Johansson, PhD, RN has, in collaboration with researchers at Goteborg University, Sweden, recently published two articles in BMC Nursing focusing on better understanding and managing pain.

In "Pain, psychological distress and health-related quality of life at baseline and three months after radical prostatectomy," Gaston-Johansson, notes that inadequate management of postoperative pain is common and is a risk factor for prolonged pain after surgery. In addition to medical and technical factors, psychological factors may also influence the experience of postoperative pain. The study found that patients who experienced the highest postoperative pain levels also had the longest hospital stay.

A second study examined unexplained chest pain (UCP), an increasing phenomenon often seen in Emergency Departments. In the article "Coping strategies, stress, physical activity and sleep in patients with unexplained chest pain" Dr. Gaston Johansson, examines coping strategies in patients with UCP and examines the relationships between these strategies, negative events, sleep problems, physical activity, stress and pain intensity.

In Other Nursing News:

David A. Thompson, DNSc, RN, and others published an article "Clinical and Economic Outcomes of Post-Operative Hospital Acquired Pneumonia in Patients who Receive Invasive Diagnostic Testing, and Ventilation" in the December issue of the "Journal of Clinical Outcomes Management." The article examines the clinical and economic impact of traditional technologies used in the diagnosis and management of intra-abdominal postoperative surgical patients who develop hospital acquired-pneumonia.

JHUSON doctoral student and clinical instructor Jason Farley MSN, MPH, CRNP, spent Thanksgiving in Namibia, Africa, working with the University of Namibia School of Nursing to complete a needs assessment for the 2007 implementation of a World Health Organization program “Integrated Management of Adolescent and Adult Illnesses.” The program supports a larger role for nursing personnel in developing countries in the care of persons living with HIV/AIDS.

Four JHUSON faculty members and doctoral students presented a variety of posters at the 134th Annual Meeting of the American Public Health Association (APHA) held in Boston, MA last month:

Rosemarie Brager, PhD, CRNP, presented "вЂ˜Guided Care’ for Multi-Morbid Adults," a model that infuses contemporary primary care with state-of-the-art information technology to help address the health care of multi-morbid older Americans in an often fragmented system lacking in quality and efficiency.

Joan Kub, PhD, APRN and SON students Jessica Williams Roberts, Sarah Joyce, Nina Fredland, and Colleen Thornton delivered posters focused on the increasingly recognized public health issue of bullying in the nation’s schools: "Bullying Victimization and Associated Health Outcomes in Elementary School Students," and "No Room for Bullying, an Intervention at a Local School."

Jodi Shaefer,PhD, RN presented “Fetal and Infant Mortality Review (FIMR): Promoting Culturally and Linguistically Competent Health Messages in Multi-Cultural Communities,” and research conducted by Robin Newhouse, PhD, RN, “Developing a Measure of the Impact of Legislation and Organizational Forces on Rural Hospital Nursing.”

The Johns Hopkins University School of Nursing is a global leader in nursing research, education and scholarship and is ranked among the top 10 nursing higher education institutions in the country. The School’s community health program is second in the nation and the nursing research program now holds eighth position among the top nursing schools for securing federal research grants. The School continues to maintain its reputation for excellence and educates nurses who set the highest standards for patient care, exemplify scholarship, and become innovative national and international leaders in the evolution of the nursing profession and the health care system. For more information, visit http://www.son.jhmi.edu/.

Johns Hopkins University School of Nursing
525 North Wolfe St, Rm 525
Baltimore, MD 21205
United States
http://www.son.jhmi.edu/

DURECT Corporation Announces Positive Phase I Study Results With New Product In Development

DURECT Corporation (Nasdaq: DRRX) announced today that it has successfully completed Phase I clinical trials with a new product, DUR-843, which is intended to treat a persistent pain condition. We believe that the persistent pain market remains underserved and that DUR-843 has the potential to provide several advantages over existing pain medications.

"We are pleased to add another product candidate to our pipeline and with the rapid progress and positive results thus far," stated James E. Brown, DVM, President and CEO of DURECT. "As a result of our recent collaboration with Nycomed covering POSIDUR, we are in a stronger financial position and therefore have decided to further develop this product on our own as part of our strategy to become a specialty pharmaceutical company. To that objective, for competitive reasons, DURECT is not disclosing at this time the specific drug delivery technology which underlies DUR-843 as well as the active pharmaceutical agent."

The objectives of the Phase I clinical studies recently completed were to determine the safety and tolerability of DUR-843 in healthy human volunteers as well as evaluate the pharmacokinetics of the active pharmaceutical agent following administration of the product candidate. In these trials, DUR-843 appeared safe and well-tolerated.

About DURECT Corporation

DURECT Corporation is an emerging specialty pharmaceutical company focused on the development of pharmaceutical systems based on its proprietary drug delivery platform technologies focused on treating chronic and episodic diseases and conditions. The Company currently has a number of late-stage pharmaceutical products in development initially focused on significant unmet medical needs in pain management, with a number of research programs underway in a variety of other therapeutic areas. For more information, please visit http://www.durect.com.

DUR-843 is a drug candidate under development and has not been submitted or approved for commercialization by the US Food and Drug Administration or other health authorities.

DURECT Forward-Looking Statement

The statements in this press release regarding DURECT's product candidate DUR-843, its attributes and commercial potential are forward-looking statements involving risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements. Potential risks and uncertainties include, but are not limited to, DURECT's ability to design, enroll, conduct and complete clinical trials, complete the design, development, and manufacturing process development of the product candidate, obtain product and manufacturing approvals from regulatory agencies and manufacture and commercialize the product candidate, as well as marketplace acceptance of the product candidate. Further information regarding these and other risks is included in DURECT's Form 10-Q dated November 3, 2006 under the heading "Risk Factors."

DURECT Corporation
http://www.durect.com

Pain Therapeutics Initiates Phase III Study With Oxytrex(TM)

Pain Therapeutics, Inc. (Nasdaq: PTIE) today announced the initiation of a Phase III study with Oxytrex, an investigational drug. Oxytrex is a unique oral painkiller for patients who suffer from persistent severe chronic pain. The Company believes Oxytrex offers less physical dependence/withdrawal than oxycodone, an 80-year-old prescription painkiller still widely used today to treat persistent severe chronic pain.

"We remain encouraged by the strong science around Oxytrex published in several top journals, including a recent article in Journal of Neurobiology that further elucidates the unique attributes of ultra-low-dose opioid antagonists," said Remi Barbier, president and chief executive officer.

This study is being referred to as the "Extreme Study" in deference to patients who depend on extremely high daily doses of oxycodone (greater than or equal to 120 mg per day) to treat severe chronic pain. The Company believes this sub-population of patients is prone to physical dependence/withdrawal.

In the second half of 2007, Pain Therapeutics plans to initiate a large study with Oxytrex in a broad patient population.

"Extreme Study" Design

This clinical study is randomized, double-blinded, multi-center and placebo-controlled. The study will enroll approximately 120 patients who have each been taking greater than or equal to 120 mg of oxycodone per patient per day for over a year. Patients who meet this and all other eligibility requirements are randomized to receive twice-daily doses of 100 nanograms (i.e., 0.0001 mg) ultra-low-dose naltrexone or matching placebo for two weeks. At the conclusion of the treatment period, patients check into a clinic and receive an injection of a high-dose opioid antagonist to precipitate withdrawal. During the withdrawal phase of the study, patients are closely monitored and measured for signs and symptoms of physical dependence/withdrawal using the Subjective Opiate Withdrawal Scale. The study's primary endpoint is prospectively defined as physical dependence/withdrawal scores in the treated arm compared to placebo. For ethical and other reasons, the study protocol allows an interim analysis.

About Oxytrex

Pain Therapeutics owns commercial rights to Oxytrex, a unique oral painkiller that preferentially inhibits an excitatory effect of opioid receptors. This excitatory effect is believed to counteract analgesia (pain relief) and cause tolerance. Its inhibition enhances pain relief and minimizes opioid tolerance. The FDA has not yet evaluated the merits, safety or efficacy of Oxytrex.

About Pain Therapeutics, Inc.

Pain Therapeutics is a biopharmaceutical company that develops novel drugs for pain management and oncology. We have three investigational drug candidates in clinical programs. Remoxy(TM) and PTI-202 are proprietary, abuse-resistant forms of opioid drugs. Oxytrex is a novel, next-generation painkiller that potentially offers less physical dependence than currently marketed opioid painkillers. We are also developing a novel radio-labeled monoclonal antibody to treat metastatic melanoma, a rare but deadly form of skin cancer. The FDA has not yet evaluated the merits, safety or efficacy of our drug candidates. For more information, please consult our website: http://www.paintrials.com/.

Note Regarding Forward-Looking Statements:

This press release contains forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995 (the "Act"). PTI disclaims any intent or obligation to update these forward-looking statements, and claims the protection of the Safe Harbor for forward-looking statements contained in the Act. Examples of such statements include, but are not limited to, any statements relating to the timing, scope or expected outcome of the Company's clinical development of its drug candidates, the potential benefits of the Company's drug candidates and the size of the potential market for the Company's products. Such statements are based on management's current expectations, but actual results may differ materially due to various factors. Such statements involve risks and uncertainties, including, but not limited to, those risks and uncertainties relating to difficulties or delays in development, testing, regulatory approval, production and marketing of the Company's drug candidates, unexpected adverse side effects or inadequate therapeutic efficacy of the Company's drug candidates that could slow or prevent product approval or market acceptance (including the risk that current and past results of clinical trials are not necessarily indicative of future results of clinical trials), the uncertainty of patent protection for the Company's intellectual property or trade secrets, the Company's ability to obtain additional financing if necessary and unanticipated research and development and other costs. For further information regarding these and other risks related to the Company's business, investors should consult the Company's filings with the Securities and Exchange Commission.

Pain Therapeutics, Inc.
http://www.paintrials.com/

Sea Snail Key To Future Of Pain Relief

Unique research at The University of Queensland could revolutionise the treatment of pain relief - thanks to a humble sea snail.

Dr Jenny Ekberg, a Research Fellow with UQ's School of Biomedical Sciences, has studied a toxin produced by a marine snail found on the Great Barrier Reef, which has the ability to precisely target chronic pain without severe side-effects.

"Chronic pain can be caused by an initial injury that affects the nerves, or conditions such as diabetes and arthritis," Dr Ekberg said.

"The problem with current drugs, such as morphine, is that they sometimes offer only marginal relief and come coupled with lots of problems with tolerance and side-effects.

"Our research show that a natural product, a conotoxin from the marine snail Conus marmoreus, produces pain relief without apparent side-effects in animal models of chronic pain."

The study, done with colleagues Professor David Adams in the School of Biomedical Sciences, Dr Richard Lewis at UQ's Institute for Molecular Bioscience and Professor Mac Christie at the University of Sydney, was recently published in the Proceedings of the National Academy of Sciences.

Dr Ekberg said with approximately one in five Australians will suffer from chronic pain at some point in their life the potential benefit of this research could be enormous.

She said sufferers of chronic pain can have the added problem of being diagnosed with no reason for the pain.

"The patient experiences severe pain because their nerve cells that are responsible for pain transmission are overactive," she said.

"This is primarily due to abnormal activity of voltage-gated sodium channels in the nerve cells.

"Conventional drugs, such as local anaesthetics, block all types of sodium channels, causing severe side-effects.

"Our toxin only blocks a specific channel - the first time a toxin like this has been shown to work - therefore providing pain relief without severe side-effects."

Dr Ekberg said it would be a number of years before such a treatment would be commercially available.

Originally from Sweden, Dr Ekberg came to UQ to complete her Honours in Biomedical Sciences and stayed to complete a PhD, from which this research stemmed, under the supervision of Professor David Adams and Associate Professor Phil Poronnik.

Dr Ekberg said she has since remained at UQ because of a combination of high-class research and a wonderful environment.

For further information please go to:
The University of Queensland, Brisbane Australia
Source:
UQ News Online

Gene Mutation Which Prevents Carriers From Feeling Pain Discovered By Cambridge Led Team

Researchers have discovered a gene mutation which prevents the otherwise healthy carriers from sensing pain, after studying three related families with a rare genetic disorder in northern Pakistan.

The research, published in the journal Nature, provides insight into the mechanics of pain and could lead to the development of more effective pain treatments.

The carriers of the very rare genetic mutation are unable to perceive any form of pain but have otherwise completely normal sensory functions. The initial case study was a ten-year-old street performer in Pakistan with the genetic mutation. His inability to feel pain enabled him to place knives through his arms and walk on burning coals. (The young boy died before his fourteenth birthday from injures sustained after jumping off a roof.)

The scientists subsequently studied six individuals with the genetic mutation from three related families, all originating from northern Pakistan. The six relatives had not experienced pain at any time in their lives. Detailed neurological examinations revealed that there was no evidence of motor or sensory disease, and that they could perceive a number of sensations (including touch, warm and cold temperature, tickle and pressure).

As pain is a survival mechanism which enables organisms to minimise damage to tissues, they had all sustained a variety of injuries, including injuries to their lips and/or tongue from biting themselves when young.

By studying these individuals, the scientists were able to determine that a mutation in the gene SCN9A causes a loss of function in the voltage-gated sodium channel it encodes (subunit Nav1.7). Sodium channels are proteins which excite neurons, and though the precise function of Nav1.7 is unclear, as part of a sodium channel it would play a role in exciting sensory neurons.

Dr Geoffrey Woods, from the Department of Medical Genetics and the University of Cambridge Institute for Medical Research (CIMR), said, “This paper shows that rare diseases can still be of great importance, because of the insights they give into biological and developmental processes".

Dr John Wood, from University College London, said, “The work of Geoff Woods and his team has provided us with an exciting new target for pain killing drugs - potentially this is as important as the identification of the morphine receptors. It is fascinating that this same gene, when mutated to encode a hyperactive channel, has also been found to contribute to ongoing pain in some heritable human disorders”.

As individuals with mutations in the gene SCN9A are otherwise healthy, the scientists are hopeful that the development of drugs that prevent Nav1.7 from functioning could be used as new and potentially safer pain medications.

###

The collaborative study, spearheaded by academics at the University of Cambridge, included researchers from a number of Pakistani and UK institutions (including University College London) and was funded in part by the Wellcome Trust.

Contact: Genevieve Maul
University of Cambridge

Genetic Mechanism Helps Explain Chronic Pain Disorders

Researchers at the University of North Carolina at Chapel Hill have discovered that commonly occurring variations of a gene trigger a domino effect in chronic pain disorders. The finding might lead to more effective treatments for temporomandibular joint disorder (TMJD) and other chronic pain conditions.

Catechol-O-methyltransferase (COMT), an enzyme that metabolizes neurotransmitters such as epinephrine, norepinephrine and dopamine and that has been implicated in the modulation of persistent pain, as well as cognition and mood, is regulated by a gene, also called COMT. Previous UNC-led research showed that common genetic variants of this gene are associated with increased pain sensitivity and the likelihood of developing TMJD.

Now, the researchers have discovered that specific variants of the COMT gene can dramatically affect the secondary structure of corresponding messenger RNA - which, in turn, leads to alterations in the amount of enzyme crucial for regulating pain processing. The discovery is published in the Dec. 22 issue of Science.

"TMJD is a complex pain condition that is frequently associated with other pain conditions such as fibromyalgia syndrome, chronic headaches and irritable bowel syndrome," said Dr. William Maixner, director of the Center for Neurosensory Disorders in UNC's School of Dentistry and a study co-author.

"This study has identified a new genetic mechanism that influences an individual's susceptibility to develop chronic pain conditions such as TMJD," Maixner said.

The study was conducted to understand the mechanism by which the identified genetic variants influence enzymatic activity and, ultimately, biological functions such as pain transmission. The researchers found that three major variants of COMT show significant differences in how they code for the secondary structure of messenger RNA, or mRNA. The differences lead to dramatic alterations in protein expression, which substantially influences pain sensitivity in humans.

These findings are clinically important because pain conditions resulting from low COMT activity or elevated catecholamine levels are likely to be susceptible to treatment with pharmacological agents that block beta 2- and beta 3-adrenergic receptors, which mediate COMT-dependent pain signaling, or that control mRNA secondary structure.

"Elucidating the genetic mechanisms that mediate pain perception will provide new insights into how chronic pain develops and will ultimately contribute to the identification of unique markers for diagnosing clinical pain conditions, as well as provide novel targets for the development of effective individualized therapeutics for TMJD and related conditions," said Dr. Andrea Nackley Neely, a research assistant professor in the Center for Neurosensory Disorders and the study's lead author.

"These data have broad medical and evolutionary implications regarding the analysis of variants common in the human population," Nackley Neely said. "It is believed that variants leading to altered protein structure have the strongest impact on gene function. However, this study demonstrates that combinations of common genetic variants that influence mRNA secondary structure may have even stronger effects and, thus, represent another key factor responsible for disease onset and progression."

"This study provides additional evidence of a genetic, molecular and physiological basis for pain perception and human pain conditions and should help to remove the stigma associated with conditions such as TMJD and fibromyalgia," said Dr. Luda Diatchenko, an associate professor in the center and the study's chief investigator.

Other researchers were Dr. Inna Tchivileva, a postdoctoral research associate within the Center for Neurosensory Disorders; Kathryn Satterfield, a former research assistant within the center; Dr. Olex Korchynskyi, a former postdoctoral research associate within the UNC-Chapel Hill School of Medicine's Thurston Arthritis Research Center; Dr. Sergei S. Makarov, a former associate professor at the Center for Neurosensory Disorders and the Thurston center and now president and chief executive officer of Attagene Inc.; and Dr. Svetlana A. Shabalina, a staff scientist with the National Center for Biotechnology Information.

Funding was provided by the National Institute of Dental and Craniofacial Research, National Institute of Child Health and Human Development and National Institute of Neurological Disorders and Stroke, all components of the National Institutes of Health. Additional support came from the Intramural Research Program of the National Center for Biotechnology Information.

Other Center for Neurosensory Disorders research initiatives are currently under way that further explore the genetic basis of pain: One seven-study, a $19-million National Institute of Dental and Craniofacial Research-funded agreement involving multiple institutions and based at the center, will follow 3,200 health individuals and 200 who have facial pain. Titled OPPERA (Orofacial Pain: Prospective Evaluation and Risk Assessment), the study is designed to identify both environmental and genetic factors that increase an individual's susceptibility to TMJD and other chronic pain conditions.

University of North Carolina at Chapel Hill
210 Pittsboro St. Campus Box 6210
Chapel Hill, NC 27514
United States
http://www.unc.edu/