Wednesday, August 28, 2013

Neuropeptide May Be Biomarker for Chronic Migraine

Levels of calcitonin gene-related peptide (CGRP), a neurotransmitter that causes vasodilation, are elevated in the peripheral blood of women with chronic migraine (CM), and to a lesser extent in women with episodic migraine, compared with levels in healthy controls without a history of headache, new research reveals.

The study shows, for the first time, increased CGRP levels in patients with CM outside migraine attacks and in the absence of medication for symptoms.

The results suggest that CGRP levels could be used as a biomarker for permanent trigeminovascular activation and therefore help diagnose chronic migraine. Until now, the diagnosis of primary headache has been based only on clinical grounds.

"It's important to have biomarkers, not only to avoid misdiagnoses but also for treatment follow-up," said study author Julio Pascual, MD, PhD, director, Neuroscience Department, and professor, neurology, University Hospital Central de Asturias, Oviedo, Spain.

"Can you imagine diagnosing and treating diabetes only on clinical grounds? That's what we do now in primary headaches. Chronic migraine is the most frequent type of almost daily headache, and it's very disabling."

The study was published online August 23 in Neurology.

Throbbing Pain

It is well established that during a migraine attack, trigeminal activation leads to release of CGRP from presynaptic nerve terminals. This facilitates a peripheral inflammatory and vasodilatory response and causes activation of neurons involved in pain transmission, the authors note. This explains the typically throbbing pain experienced by people suffering a migraine.

CM is defined at least 15 headache days per month for at least 3 months. Fewer than 15 headache days per month is considered episodic migraine (EM).

Using the right antecubital vein, researchers obtained blood samples from participants who were not experiencing moderate or severe pain and had not taken medication for symptoms in the previous 24 hours. For ethical reasons, participants could continue daily preventive medications, and most with migraine were taking these agents. The investigators determined CGRP levels using a commercial enzyme-linked immunosorbent assay kit.

The study included 103 women with CM (mean age, 43.1 years), 31 matched healthy women with no headache history (mean age, 38.6 years), 43 women with EM (mean age, 44.4 years), and 14 patients with episodic cluster headache (including 13 men; mean age, 45.4 years) matched for age in a pain-free period.

Study participants underwent a general physical and neurologic examination. Those with EM and CM had at least a normal neuroimaging examination.

The analysis showed that CGRP levels were significantly higher in women with CM (74.90 pg/mL) than in control women (33.74 mg/mL; P < .001), women with EM (46.37 pg/mL; P < .001 vs CM and P < .005 vs controls) and to patients with episodic cluster headache (45.87 pg/mL).

"Increased peripheral CGRP levels should be interpreted as a distant sign of activation of the trigeminovascular system; because its molecule is so large, CGRP cannot pass the blood-brain barrier," said the authors.

Thresholds of 43.45 and 58.22 pg/mL optimize the sensitivity and specificity to differentiate patients with CM from healthy controls and patients with EM, respectively, according to the authors.

Migraine With Aura

A total of 46 women with CM had a history of migraine with aura attacks. CGRP levels were significantly higher in these women than in those who had never experienced an aura. However, only 4 patients experienced at least 1 aura per month.

According to the authors, there are several potential explanations for this finding. It could, for example, support the proposal that the pathophysiologic mechanism of the aura, the cortical spreading depression phenomenon, is enough to activate sensory nerve terminals around pial blood vessels.

Among women with EM, CGRP was not significantly elevated in the 21 women with aura compared with the 22 with no aura antecedents.

Among the women with CM, CGRP levels were not significantly different in patients meeting criteria for analgesic overuse. "Even considering that all of the women in our study with CM meeting overuse criteria had tried formal withdrawal of symptomatic medications at least once and for 2 months without success, these results are a further proof that both subtypes of CM, with and without analgesic overuse, would share the same pathophysiologic substrate," the authors write.

Other variables, such as age, depression, fibromyalgia, vascular risk factors, history of triptan use, and type of preventive treatment, also did not influence CGRP levels.

The fact that patients were taking preventive medications could be considered a limitation of the study but could also make the results more relevant because, as the authors point out, these drugs could reduce trigeminovascular system activation, resulting in a decrease in CGRP release.

Although the new study had other potential limitations, such as the use of a select headache clinic population, "it seems that interictal CGRP levels are somewhat specific and sensitive for CM in the context of a patient with daily or almost daily headaches and a history of migraine, which could be of great help on sharpening the diagnosis of the primary headache disorders and supports the proposal of a key role of CGRP of sensitization of pain circuits leading to CM," the authors concluded.

Using CGRP as a biomarker for CM may not be that far off from clinical practice, if the current results are confirmed in other studies using this neuropeptide, perhaps together with other pain-producing peptides, said Dr. Pascual. Such studies, he said, would not be difficult to carry out.

"My prediction is that clinical trials in chronic migraine that include the follow-up of CGRP levels will begin soon after publication of our study," he said.

And, he said, it won't be long before hospitals will start using CGRP levels to routinely follow patients with CM because this testing is neither very expensive nor difficult to perform.

Monitor Status

In an accompanying editorial, Stephen D. Silberstein, MD, Jefferson Headache Center, Jefferson Center for Neuroscience, Philadelphia, Pennsylvania, and Lars Edvinsson, MD, Internal Medicine, Lund University, Sweden, agreed the study demonstrates that peripheral CGRP levels may be a biomarker for CM.

Physicians could use CGRP levels outside migraine attacks, and in the absence of medication for symptoms, to monitor a patent's status and response to preventive treatment, they write.

"Future work on the role of CGRP and its receptor in CNS and intracranial structures will be very interesting," they write. "In particular, we look forward to learning more about the effects of small-molecule CGRP antagonists and antibodies toward CGRP and the CGRP receptor on CGRP levels and clinical outcome."

They noted that until now, CGRP elevations in plasma have not been reproduced in all studies but that technical problems have at times hampered the proper measurements of this neuropeptide.

Thursday, August 22, 2013

Bacteria can cause pain on their own | Genes & Cells | Science News

Bacteria can directly trigger the nerves that sense pain, suggesting that the body's own immune reaction is not always to blame for the extra tenderness of an infected wound. In fact, mice with staph-infected paws showed signs of pain even before immune cells had time to arrive at the site, researchers report online August 21 in Nature.

"Most people think that when they get pain during infection it's due to the immune system," says coauthor Isaac Chiu of Boston Children's Hospital and Harvard Medical School. Indeed, immune cells do release pain-causing molecules while fighting off invading microbes. But in recent years scientists have started uncovering evidence that bacteria can also cause pain.

Chiu and his colleagues stumbled on this idea when they grew immune cells and pain-sensing cells together in a dish. The researchers were trying to activate the immune cells by adding bacteria to the mix but were surprised to see an immediate response in the nerve cells instead. This made them suspect that nerve cells were sensing the bacteria directly.

To take a closer look at a real infection, the team injected the back paws of mice with Staphylococcus aureus, a bacterium that causes painful sores in humans. The researchers measured how tender the infected area was by poking it with flexible filaments of plastic. If the mouse didn't like being prodded, it would lift its paw, giving a sensitive measure of each infection's ouch factor.

The mice's paws were most sensitive when bacterial cell numbers were at their peak, six hours after infection. By the time the immune response caught up, at 48 hours after infection, the pain had largely ebbed away. The researchers identified two protein factors released by S. aureus that could trigger nerve cells in dishes and that were also painful when injected into the mice.

These factors seemed to be more important than the immune system in making mouse paws achy, since mice with faulty immune responses were at least as tender as normal mice, the researchers report. However, pain from immune reactions might play a more significant role in other kinds of infections, Chiu cautions, since not all bacterial species are as good as S. aureus at evading the immune system.

The team guessed that the nerves were helping to alert the immune system to the presence of bacteria, but when they tested this idea, they got a surprise. "We saw the opposite of what we expected," Chiu says. When the researchers infected mice that lacked pain-sensing nerve cells, even more immune cells rushed to the site of infection than in normal mice. This implies that the nerve cells normally suppress the immune system, Chiu says.

Chiu doesn't know why pain should dampen the body's defenses against pathogens but speculates that when tissue is damaged by injury, an overenthusiastic immune system may need to be held back. Bacteria like S. aureus might take advantage of pain's anti-immune effects to avoid detection, he suggests, "but it's an open question."

Kevin Tracey, an immunologist and president of the Feinstein Institute for Medical Research in Manhasset, N.Y., says the results fit with his own studies that show nerve signals can put the brakes on immune responses. "It's a beautiful study," Tracey says. "It's important because it shows that in order to understand the immune system, you really have to understand the nervous system."

Saturday, August 17, 2013

The Color of Pain | Illusion Chasers, Scientific American Blog Network

Want to know an effective way to reduce pain from burns? Cover the affected red area, so you are unable to look at it. Ideally, use a blue bandage. Painfully hot stimuli applied to red skin feel more painful than applied to blue skin, a new research article published in Frontiers in Human Neuroscience shows.

The scientists, Matteo Martini, Daniel Perez-Marcos and Maria Victoria Sanchez-Vives from  the University of Barcelona, used immersive virtual reality in combination with the application of real heat stimuli to the wrists of experimental subjects. Participants saw their virtual arms get increasingly red, blue, or green as the heat rose, and indicated, by pressing a button, when the sensation became painful. In an additional experimental condition, a gray dot close to the virtual arm became red as the temperature increased, but the color of the arm itself remained unaltered.

The experimental set-up and the four experimental conditions. The participant saw the virtual environment through a head mounted display. When the participant felt the heat stimulation as painful, she stopped the stimulation by pressing a button with the other hand (A). The participant's arm resting on the table matches the avatar's posture (B). First-person perspective view of the avatar while the skin color changed into blue (C), red (D), or green (E). In the fourth condition, the skin of the virtual arm did not change color but a gray spot on the table turned into red (F).

The results showed that subjects experienced pain earlier (that is, at lower physical temperatures) when the arm was red than when it was blue.

Pain thresholds in each condition. Asterisks indicate significant comparisons (*p < 0.05; **p < 0.01)

Also, the experience of increased pain was not associated to seeing red per se, but it mattered whether the color was on the body or not. A patch of red near –but not on– the virtual arm resulted in significantly less pain than that recorded with the arm itself becoming red.

So much for looking at life through rose-colored glasses.

See more pain illusions in our new article in Scientific American Mind, in the  September 2013 print edition.


Wednesday, August 14, 2013

Throbbing pain isn’t a matter of the heart, UF researchers find » News » University of Florida

Throbbing pain may pound like a heartbeat, but University of Florida scientists have discovered the sensation is all in your head, or more precisely, in your brain waves.

The finding could drastically change how researchers look for therapies that can ease pain, said Dr. Andrew Ahn, a neurologist at the UF College of Medicine, a part of UF Health. Ahn and his colleagues reported their findings in the July issue of the journal Pain.

"Aristotle linked throbbing pain to heart rhythm 2,300 years ago," Ahn said. "It took two millennia to discover that his presumption was wrong."

People who have experienced a toothache or a migraine — or even just hit their shin on the coffee table — may have noted a throbbing quality to the pain that physicians have long associated with arterial pulsations at the location of the injury. Some medicines even constricted blood vessel walls in hopes of lessening the effect.

"Current therapies for pain do not adequately relieve pain and have serious negative side effects, so we thought that by examining this experience more closely we could find clues that would lead us to improved therapies to help people who suffer from pain," Ahn said. "It turns out that we have been looking in the wrong place all along."

Ahn and his colleagues had previously examined the pulsations associated with throbbing pain while monitoring heart rate and found the two were not linked. This observation can be verified by almost anyone experiencing throbbing pain, by comparing their throbbing experience with their own pulse. At the time, researchers did not have an alternative explanation for the origin of the throbbing quality of pain, but this current case study reveals new answers.

Ahn and his colleagues Jue Mo and Mingzhou Ding in the UF College of Engineering along with Morris Maizels of the Blue Ridge Headache Center in Asheville, N.C., examined a patient who had a throbbing sensation that remained even after her chronic migraine headaches had resolved. They simultaneously recorded the patient's sensation of the throbbing pain and her arterial pulse and found that they differed from one another, indicating that the pulsing of blood from the heartbeat was unrelated to the throbbing quality of pain.

However, through the use of an electroencephalogram, they found that the throbbing quality was correlated with a type of brain activity called alpha waves.

"We understand very little about alpha waves, but they appear to have an important role in attention and how we experience the world," Ahn said. "In addition, by analogy to how a radio works, alpha waves may also act as a carrier signal that allows different parts of the brain to communicate with itself."

What scientists don't know yet is exactly how alpha waves cause throbbing pain. But the current findings indicate that the experience of pain is linked more to how the brain works and not to the pulsations of blood at the location of the pain. Understanding this will allow researchers to design new studies to discover better treatments for pain, Ahn said.

Study Finds ‘Doctor Shopping’ Uncommon - National Pain Report - National Pain Report

Less than one percent of patients – about 135,000 people — who purchase prescription painkillers in the U.S. were classified as "doctor shoppers" in the first national study of opioid prescriptions and sales records.

But while they make up only a small proportion of the 48 million patients who are prescribed painkillers, researchers say patients who visit multiple doctors and pharmacies to obtain opioids are having an outsized impact on the system. Federal and state officials have cracked down on the illicit use of painkillers by making it harder for patients to obtain opioids – even ones with legitimate prescriptions.

The study found that the vast majority of patients prescribed opioids did not abuse the drugs or visit a suspicious number of doctors.

"We estimate that a small outlying population of approximately one of every 143 patients who purchased opioids from retail pharmacies in 2008 obtained these prescriptions from a suspiciously large number of different prescribers. Patients in this population got an average of 32 prescriptions from an average of 10 different physicians," wrote researchers Douglas McDonald and Kenneth Carlson of Abt Associates.

The study, published online in the journal PLOS ONE, analyzed records for over 146 million prescriptions dispensed in 2008 for opioids containing buprenorphine, codeine, fentanyl, hydrocodone, methadone, oxycodone, oxymorphone, propoxyphene, or tramadol.

The drugs were prescribed by over 900,000 doctors, dispensed by about 37,000 pharmacies, and given to over 48 million patients.

Patients classified as doctor shoppers purchased 4.3 million prescriptions, or nearly 2 percent of all opioid prescriptions sold in 2008. Some doctor shoppers saw over 200 different physicians that year, often crossing state lines to obtain prescriptions.

"The amounts of opioids purchased by patients in this extreme population are another strong signal of doctor shopping – an estimated average of 109 morphine equivalent milligrams per patient per day for the entire year. Even if these patients did not divert drugs for illicit purposes, obtaining opioids from such large numbers of prescribers may signal dangerously uncoordinated care," the researchers said.

The risk of abuse was highest for oxycodone (2.8% of all prescriptions) and oxymorphone (2.3%). The lowest risk of abuse was for codeine (1.2%), fentanyl (1.2%), methadone (1%), and propoxyphene (1%).

To prevent abuse, most states have created prescription drug monitoring programs (PMPs) to collect sales records of painkillers. But studies have found that many physicians do not access PMPs before writing patients' prescriptions. Many PMPs are not "user friendly" and often have rules that frustrate doctors. Physician awareness about the tools is poor, and some states restrict access, opening the database only to law enforcement officials.

"Ultimately, the front lines of defense against drug diversion by deceptive patients are manned by physicians and other healthcare providers who are authorized to prescribe scheduled drugs. Many of these providers are ill prepared," the researchers said.

"Pain management has not been traditionally been a part of the curriculum in medical schools and surveys of physicians have found their knowledge of pain management principles to be deficient."

The researchers said physicians could prevent doctor shopping by screening new patients for their risk of abuse and by monitoring their adherence to prescribed treatments. They also recommend that PMPs and health insurers scan prescription data to flag suspicious activity that may indicate doctor shopping, and then alert physicians and pharmacists about the patients.

The study found that most patients who were prescribed opioids did not abuse the drugs or used them sparingly.

Among patients using opioids during the first 2 months of 2008, 43% did not use the drugs for the rest of the year. Of those patients who continued to use opioids, 31% received their prescriptions from 1 physician and 14% from 2 physicians. About 3% of patients obtained prescriptions from 5 to 9 prescribers.

Backlash Against Walgreen’s New Painkiller Crackdown | CommonHealth

You may be in for a shock if you try to get a prescription for any controlled substance – from Ambien to opioid pain relievers – filled at Walgreens anywhere around the country.
Walgreens recently announced what it calls a new “Good Faith Dispensing” policy under which the pharmacy giant – the largest in the nation – is suddenly requiring its pharmacists to take “additional steps” to verify prescriptions for controlled substances.
In plain English, this means that Walgreens pharmacists are going to call your doctor, or at least your doctor’s office, to see if your doctor did the right thing in giving you a prescription for pain relievers and other drugs. The policy is provoking distress and outrage among pain patients, physicians and others.This process, the company says, “may, at times, require” the pharmacist to contact the prescribing doctor to make sure the diagnosis, the exact billing code, the expected length of therapy and “the previous medications/therapies tried and failed” are correct.
In a telephone conversation, a Walgreens spokesman denied that the aggressive new policy was specifically triggered by the Drug Enforcement Administration’s crackdown on the company in the wake of problems with infamous “pill mills” in Florida. Until recently, unscrupulous “patients” and unscrupulous doctors in Florida have colluded in diverting massive quantities of prescription pain relievers such as oxycodone (an ingredient in OxyContin) through fake clinics dubbed “pill mills.”
In June, Walgreens and the DEA announced an $80 million settlement to resolve the government’s charges that Walgreens failed to control the sales of opioid pain relievers in some of its stores.
The government said that distributors of pain relievers failed to monitor suspiciously large orders for opioids Necessary as that crackdown was, a presumably unintended result is that legitimate pain patients are finding it harder to get the medications they need.
Walgreens spokesman Michael Polzin told me that he was not sure precisely when the company’s “Dear Valued Prescriber” letter spelling out the new policy went out, adding that he thought it went out in April or early summer. (There is no date on the letter itself). The date of the DEA settlement was June 11, 2013.
Although pain patient advocates worry most about getting prescriptions for opioid pain relievers, Polzin confirmed that the letter actually stipulates new procedures for all controlled substances. In theory at least, that could make it harder for patients to get prescriptions for other drugs such as Restoril, Halcion, Sonata, Ambien and Lunesta.
Asked why Walgreens is taking this action now, Polzin said, “There’s been, as is well known, a sharp rise in the abuse of prescription painkillers in recent years and health care professionals of all practices are being asked to find better ways to make sure those medications are used for legitimate purposes.”
Asked specifically if the $80 million settlement imposed by the DEA triggered the company’s actions, Polzin said, “We actually imposed our Good Faith Dispensing policy before that settlement. We have done a number of things before reaching the agreement with the DEA to make sure we were fulfilling the obligations for dispensing controlled substances and making sure that our training and pharmacy staff were where they needed to be.”
He acknowledged that the new policy may mean that getting prescriptions filled “could take extra time – it does require us at times to get information from physicians’ offices.”
Whatever the motivation by Walgreens, the American Medical Association is furious. In a resolution in late June, an AMA committee chaired by Iowa dermatologist Marta van Beek called the Walgreens’ policy a direct “intrusion into medical practice.”
As the AMA committee put it, “pharmacists are not and under no circumstances should be required to confirm the appropriateness of a prescription; this decision is a purely medical one, completely in the purview of the treating physician.” The policy “will be very disruptive to physicians’ practices, interrupting visits and procedures and delaying other patients’ care.” The Walgreens policy may also seriously delay “delivery of medications to all patients.”
Van Beek added, in an email to me, “The physician-patient relationship is focused on the patient’s disease and how best to treat it in the context of the patient’s health and social factors. A pharmacy does not have this perspective.”
US Representative Michelle L. Grisham, a Democrat from New Mexico and a former secretary of health in that state, is also worried that the Walgreens’ policy “is endangering the health and safety of patients by delaying the filling of opiate prescriptions.” The policy may force patients “to go to multiple pharmacies to fill prescriptions, which could put patients in jeopardy with state Prescription Drug Monitoring Programs, she said in a letter to the New Mexico Board of Pharmacy.
In a telephone conversation, Grisham went further: Walgreens “policy is very over-reaching..[they] are vilifying the patient, which is outrageous.”
Some pharmacists don’t seem to like the new Walgreens policy, either. On a website, one member of the group, speaking for himself, blogged that the policy as “the height of corporate self-interest.” That view does not reflect the policy of the society.
Pain patient Cindy Steinberg, national director of policy and advocacy at the Connecticut-based US Pain Foundation, acknowledges that “a pharmacist “is entitled to look for the authenticity of a prescription.” But, she told me, “this is now going over the line into judging the appropriateness of a prescription. That is outside pharmacy practice. They can’t question whether a physician can or should institute this therapy…“this is very harmful for people with pain who are simply trying to get their medications so they can have some quality of life.”
The new Walgreens policy is creating particular problems for pain patients in Florida. One South Florida chronic pain patient, Julee Payne, wrote me that she has filled her prescriptions with Walgreens for over 10 years. But now, she said, “we’re expected to drive around for hours to find a pharmacy who will/can fill our medications…”
The result of the new Walgreens policy, she said, is that pharmacists “have been given the absurd task of policing the doctors on top of everything else….It is truly a public health crisis here.”
Judy Foreman, a longtime syndicated health columnist, is the author of the forthcoming book “A Nation in Pain – Healing Our Biggest Health Problem,” from Oxford University Press.
Update from Judy Foreman: A previous version of this story incorrectly left the impression that the American Society of Health-System Pharmacists as a whole was highly critical of a new Walgreens’ policy called “Good Faith Dispensing.” That was in fact a view expressed in a blog by one individual member of the group posted on June 15, 2013 and does not represent the opinion of the organization as a whole; that opinion was expressed in an official blog on July 22, 2013. We regret the error.

Monday, August 12, 2013

SciBite: Latest pharma & biotech news and competitor intelligence for Pain

Risk of Adult Anxiety Seen in Children’s Stomachaches -

Children with chronic stomach pains are at high risk for anxiety disorders in adolescence and young adulthood, a new study has found, suggesting that parents may wish to have their children evaluated at some point for anxiety.
Researchers at Vanderbilt University tracked 332 children with recurring stomachaches that could not be traced to a physical cause — so-called functional abdominal pain — comparing them as they reached young adulthood with 147 children who had never had such stomachaches.
About half the teenagers and young adults who had had functional abdominal pain as children developed an anxiety disorder at some point, compared with 20 percent of the control group, the researchers found. The vulnerability to anxiety persisted into adulthood even if the pain had disappeared, although the risk was highest if the pain continued.
Forty percent of the children with functional abdominal pain went on to experience depression, compared with 16 percent of those who had never had these stomachaches.
The study was published on Monday in the journal Pediatrics.
"What this study shows is a strong connection between functional abdominal pain and anxiety persists into adulthood, and it drives home the point that this isn't by chance," said Dr. John V. Campo, chairman of the department of psychiatry at Ohio State University, who was not involved in the new study.
In 2001, Dr. Campo published a smaller study that found that 28 young adults who had suffered functional abdominal pain as children were far more likely to have an anxiety disorder than 28 similar adults who had experienced another childhood illness.
Chronic abdominal pain affects 8 percent to 25 percent of school-age children. The problem can lead to school absences and take a toll on families.
"Somebody might say, 'Of course they have mental issues or they are emotionally distressed — it's because of the pain,' " said Lynn S. Walker, senior author of the study and director of the division of adolescent health at Monroe Carell Jr. Children's Hospital at Vanderbilt.
"But we found even if the pain went away, these adolescents and young adults still have anxiety," Dr. Walker said. "So maybe we need to treat their anxiety."
The state-of-the-art treatment for functional abdominal pain is rehabilitative, focused on getting patients to participate in daily activities despite their stomachaches. "There's no question that there are triggers for the pain, but the problem is in the perception of the pain and adaptation to the pain," said Dr. Samuel Nurko, director of a functional abdominal pain center at Children's Hospital Boston.
Dr. Nurko compared the pain to a light on a dimmer switch, which psychological techniques can help children control. "You don't take away the pain," he said. "You 'dim' it to be able to cope better."
The new study underscores the importance of screening children with the condition for anxiety or depression, the authors said. Anxious children tend to be good children who are concerned about doing their best, Dr. Walker said, and parents may be flummoxed by the suggestion that such a child could be grappling with a mental health issue.
The majority of the children enrolled in the study "had not seen a mental health professional, ever," Dr. Walker said.
But Miranda van Tilburg, an associate professor of medicine at the University of North Carolina School of Medicine, cautioned parents against leaping to the conclusion that a child's unexplained stomach pain is "all anxiety based, because we don't know that."
"The take-away message should be you should not be afraid, if your doctor talks to you about anxiety in your child, to seek help from a mental health professional, because it could help your child feel better," Dr. van Tilburg said.
Such a referral is "not an admission that that's what's causing the pain," she said. "It's just an admission that anxiety is linked to the pain."
Nasrin Kazemi, a part-time real estate agent in Brentwood, Tenn., has three children, all of whom had frequent stomachaches. "If I get a little more excited, or sad, or mad about something, my stomach will start hurting," said Mrs. Kazemi's youngest daughter, Donya, 11.
The anticipation of starting sixth grade this fall has set off new waves of stomach pain. "It's probably not going to stop until I get used to sixth grade," Donya said.
She became anxious two years ago after a ghastly fortnight of flu-induced vomiting, her mother said. Since then, Donya worries about attending birthday parties where she might catch another flu, and such concerns make her abdominal pain flare up.
At first, Mrs. Kazemi was reluctant to seek psychological help for Donya, but her daughter eventually saw Dr. Walker. Mrs. Kazemi is hopeful about the new research, even though it suggests that Donya may have a lifelong vulnerability to anxiety.
"Because she is learning to deal with her emotions and to not let them get the better of her, she'll be better with dealing with negative things that happen later in life," Mrs. Kazemi said.

Wednesday, August 07, 2013

An End to Sunburn Pain: Scientists Say It’s Possible |

For sun worshipers, the sting of the sunburn is sometimes the price of bronzed skin, but it doesn't have to be that way, according to researchers.

Wolfgang Liedtke, a Duke University neurologist, and scientists from Rockefeller University and the University of California San Francisco discovered that by blocking a molecule called TRPV4, they can eliminate the chain of events that result in the pain caused by sunburn.

Most sunburns are triggered by ultraviolet B rays (UVB) that damage the skin's outermost layer, which can result in redness and burning. In moderate amounts, exposure to UVB rays can be beneficial, launching the body's vitamin D-making processes. But with intense exposure, UVB rays can contribute to skin cancer and accelerate skin aging as well. In their findings, published in the Proceedings of the National Academy of Sciences (PNAS), Liedtke and his colleagues showed they could halt the process by which UVB rays irritate skin cells in both mice and people.

UVB rays activate TRPV4 to allow calcium ions into skin cells, and lead to secretion and increased production of another molecule called endothelin, which causes pain and itching. The researchers identified this pathway after they bred mice that were missing TRPV4 in the outer layer of the skin on their hind paws, which resembles human skin. When their paws were exposed to UVB rays, the mice showed little change or pain to their skin, while normal mice with TRPV4 developed blisters and redness.

Liedtke saw similar increases in TRPV4 and endothelin in biopsy specimen of human skin, which suggests the same pathway is involved in people's responses to UVB rays.

But most importantly, he and his team also showed that by blocking the activity of TRPV4 with a solution containing an experimental agent that inhibits TRPV4 that was applied to the hind paws of the normal mice, the mice showed little adverse reaction to the UVB exposure and were significantly less affected by pain.

The researchers are still unsure whether the process actually protects the skin from long-term UVB exposure damage–or if it simply blocks the sensation for pain. That's important, since sunburn and the pain associated with it are signals that skin has reached its limit of sun exposure — and for people, that's an alert to get out of the sun and into the shade.

"[TRPV4 inhibitors] will have to be used together with sunscreen because of the yet unknown issue of the long-term damage by UV rays on cell growth and on the damage it can have on DNA and the DNA structure," says Liedtke. "We need to look into whether and how much the calcium influx through the TRPV4 channel is linked to that type of damage. It's possible the calcium influx makes defense mechanisms stronger, or weaker. It could also be that the calcium accelerates the damage."

So for now, the researchers envision that TRPV4 blockers would be used in tandem with sunblock. According to the International Business Times, there are quite a few pharmaceutical companies that are already producing TRPV4 blockers:

But even if the inhibitors don't prove helpful in protecting against sunburn pain after exposure, they will likely work preventively Liedtke says the results highlight the role that skin may play in other pain-related reactions. "This plays into a direction that some research has taken in implicating the skin as having a more proactive role in pain symptoms — for instance, skin inflammations, in which skin cells are obvious contributors to the pain response. But there has also been research suggesting that even [in] bone fractures where the bone is close to the skin, the pain of that is modulated and enhanced by the skin cells," says Liedtke.

There won't be a solution to sunburn pain in time for the last sunny days of summer, but the findings could pave the way for soothing treatments in summers to come. In the meantime, the best way to treat sunburn pain is to avoid inflaming the skin in the first place — wear sunscreen and avoid the sun's most intense UV rays, between 10am and 4pm.