chronic pain

#Chronic pain: are #psychological interventions beneficial?

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  • Noticias Médicas Univadis

Psychological therapies may have a small, but statistically significant benefit for reducing pain among older adults with chronic pain, according to findings of a new systematic review and meta-analysis on the subject published in JAMA Internal Medicine.

The findings come at a time when there is an increased focus on non-pharmacologic therapies for chronic pain that use cognitive behavioural therapy approaches.

Researchers examined data on 2,608 participants from 22 studies and found psychological interventions that used cognitive behavioural therapy modalities were associated with statistically significant benefits in terms of reduced pain and catastrophizing beliefs as well as improved self-efficacy for managing pain. “Benefits were small and documented at the time of treatment completion; with the exception of pain reduction, evidence is lacking for the persistence of observed benefits in other assessments conducted up to six months later,” the authors said.

The observed benefits were strongest when delivered using group-based approaches with the authors suggesting access to peer support, social facilitation of target behaviours, and public commitment to therapy goals may account for this finding.

“Research is needed to develop and test strategies that enhance the efficacy of psychological approaches and sustainability of treatment effects among older adults with chronic pain,” the authors concluded.

#CBT for #Chronic Pain May Help Fight the #Opioid Epidemic

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Batya Swift Yasgur, MA, LSW

Cognitive-behavioral therapy (CBT) appears to be an effective alternative to opioids for chronic nonmalignant pain, either as a stand-alone treatment or in combination with other nonopioid medications, new research shows.

Investigators at Drexel University College of Medicine, Philadelphia, describe CBT as a “useful and empirically based method of treatment for pain disorders that can decrease reliance on the excessive use of opioids.”

“There is a population that may legitimately need chronic opioid treatment, but most people’s pain can be managed with CBT or acceptance and commitment therapy and, if necessary, nonopioid pharmacotherapy as well as physical and occupational therapy,” study investigator Muhammad Hassan Majeed, MD, attending psychiatrist, Natchaug Hospital, Mansfield Center, Connecticut, told Medscape Medical News.

The study was published in the November issue of the Journal of Psychiatric Practice.

Growing Evidence Base

Dr Majeed said his interest in the use of nonopioid therapies dates back to when he worked in an opioid addiction treatment center.

“Many of the patients had the story of starting on opioid therapy for chronic pain and then escalating to aberrant use and abuse of opioids. Some were on a decent dose of suboxone but were still complaining about pain. I thought, ‘something is missing here,’ ” he said

Dr Majeed contacted study coauthor Donna M. Sudak, MD, professor of psychiatry, Drexel University College of Medicine, Philadelphia, who had been the program director during his psychiatric residency as well as past president of the Academy of Cognitive Therapy.

“We decided to collaborate on this article to further bring to light the role of CBT in treating chronic pain,” he said.

Their article reviews the “growing evidence base,” which encompasses neuroimaging studies, systematic reviews, and randomized trials of CBT in the treatment of chronic pain. They concluded that CBT is “efficacious and cost-effective,” with “long-lasting” impact.

By contrast, no empirical evidence supports the use of opioids for the treatment of chronic noncancer pain lasting more than 1 year. In fact, long-term opioid use is associated with a host of serious risks, including misuse, abuse, addiction, overdose, and death, the authors point out.

Despite the lack of evidence, there has been a “steady increase” in the use of opioid prescription for this indication during the past 2 decades, during which there has been a “steady rise” in opioid-related disorders and deaths from overdose.

The authors attribute the “recent surge in prescription opioid pain medication addiction in the United States” to “aggressive marketing and excessive dispensing” of these agents in the primary care setting.

A Delicate Balance

“When considering long-term opioid treatment for chronic pain, the physician must balance the risk of addiction against the goal of a functioning life,” the authors note.

Patients often request opioids, believing them to be the only means of achieving pain control and functionality. Physicians often prescribe them for this purpose.

Dr Majeed described visiting a pain clinic and observing a patient with chronic headaches. The patient was already being treated with clonazepam for insomnia. The physician prescribed an opioid so that the patient could be pain free and able to function at her child’s wedding.

“I did not want to jump to conclusions because she was not my patient and I had no long-term knowledge of her situation, but I wondered if there were not other nonopioid approaches to increasing this patient’s functionality and reducing her pain for this event.”

The authors advise physicians to discuss the pros and cons of opioid treatments and explore alternatives. Patients may be able to tolerate decreasing their opioid agents in “small increments” as they introduce alternative modalities so that the transition does not impair their functioning.

Dr Majeed added that physicians should discuss with their patients day-to-day functioning as a major treatment goal and that physicians should emphasize to patients that functioning is “more important than the numbers on the pain scale.”

Breaking a Vicious Cycle

The authors characterize the goal of CBT for pain disorders as reconceptualizing “the idea of pain from ‘pain means tissue damage’ and, if no source is found, ‘it’s all in your head’ to the idea that all pain is ‘in the head,’ and that multiple factors influence the perception of pain.”

Reframing pain in these terms enables the patient to begin seeing himself or herself as “a well person who has pain,” thereby lessening the preoccupation with pain and medical help-seeking.

The authors explain that patients with pain often think they would damage their body if they were active. This leads to inactivity, deconditioning, and increasing disability.

This cycle of inactivity and persistent help-seeking centralizes pain as the organizing principle in the patient’s life. Moreover, “the patient becomes governed by fear of pain, and the fear is worse than the real thing,” Dr Majeed commented.

The role of CBT is to help patients recognize the emotional and psychological factors that influence pain perception and the behaviors associated with having pain.

CBT tests the patient’s assumptions about the frequency and severity of pain and its association with activities. It encourages patients to engage in “behavioral experiments” that gradually enable them to engage in “meaningful work projects” and “pleasurable family activities.”

Tasks are divided into small components, and each goal is accomplished incrementally. Relaxation and meditation exercises are used to “manage tension and assist the patient to observe sensations without judgment.”

Cognitive strategies challenge the patient’s beliefs and thoughts about the pain. Then, using cognitive restructuring, the patient learns to modify thoughts to “increase accuracy and usefulness” and use “positive coping self-statements.”

The authors characterize acceptance and commitment therapy as an evidence-based cognitive and behavioral approach that increases effective functioning by helping the patient to accept suffering, use mindfulness, and increase activity and behavior in the service of the patient’s goals and values.

Psychiatrists as Gatekeepers

At present, primary care practitioners are the “gatekeepers” for pain management, Dr Majeed said.

Unfortunately, in the primary care setting, opioids are frequently overprescribed and nonpharmacologic interventions are underutilized. Reasons for this include lack of familiarity on the part of practitioners as well as time pressure, patient demands, ease of prescribing, and low reimbursement rates for psychotherapies.

Dr Majeed suggested that the psychiatrist should assume the role of gatekeeper of a multidisciplinary team that includes primary care practitioners, physical and occupational therapists, psychotherapists who deliver CBT and acceptance and commitment therapy, and pain specialists.

The role of the psychiatrist is particularly important because chronic pain is “complex and multifaceted.” It often occurs in association with depression and anxiety.

“The psychiatrist should define and interpret the goals of treatment, determine how much the pain is interfering with daily life, and prescribe nonopioid pharmacotherapies, such as antidepressants and anticonvulsants, when appropriate, which are medications that psychiatrists prescribe on a regular basis.”

Psychiatrists may also need more training in dosing and prescribing these agents specifically to treat chronic pain and in addressing opioid-related clinical decisions and management, he said.

Practitioners also need training in how to integrate the use of CBT into the treatment of chronic pain. This training may be “resource-intensive,” but may help “ease the clinical, financial, and social burden of pain disorders on society,” the authors emphasize.

Therapeutic Alliance

Many patients with chronic pain are particularly sensitive to receiving a referral to a mental health professional because they believe they are being told that their distress is not “real.” The authors encourage therapists to be attuned to this problem and to focus on building a therapeutic alliance.

“Concerns may be alleviated by emphasizing that many patients with chronic health conditions have benefited from mental health care and learning to cope better with the stressful demands of illness,” the authors advise.

Dr Majeed added that it is important to remind patients that clinicians will work collaboratively with them to create a treatment plan that might include medications or procedures if appropriate

No funding for the study has been described. The authors have disclosed no relevant financial relatioships.

J Psychiatr Pract. 2017;23:409-414. Full text

#Acupuncture for #Chronic Pain: Unprecedented Advances

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Pauline Anderson

SAN DIEGO — The last two decades have seen “unprecedented advances” in the use of acupuncture to treat pain conditions, with a “rapid rise” in the number and quality of related published studies, according to a physician who is an experienced acupuncture practitioner.

“Right now, we have a pretty solid foundation for the efficacy of acupuncture” for headache, osteoarthritis (OA), and musculoskeletal conditions, said Farshad M. Ahadian, MD, clinical professor of anesthesiology, University of California, San Diego.

“I think it’s fair to say that acupuncture is here to stay. It’s going to be a permanent addition to our tool box.”

Dr Ahadian presented the data here at the Academy of Integrative Pain Management (AIPM) 28th Annual Meeting.

Opioid Epidemic Rages On

To reach their “full potential,” clinicians need to “fully integrate” conventional medicine with alternative therapies, which includes acupuncture, Dr Ahadian told meeting delegates.

This may be increasingly important because of two “really important critical challenges”:  the opioid epidemic and the aging population.

“The opioid epidemic has been raging for two decades, and there seems to be no end in sight. And I don’t think we have woken up to the implications that an aging population has for the prevalence of chronic pain.”

During his presentation, Dr Ahadian reviewed some of the extensive literature on acupuncture for chronic pain. Between 1997 and 2010, over 600 related clinical trials were published.

One recent review,  which Dr Ahadian described as “one of the most academically rigorous” analyses, was independently funded by the National Institute for Health Research in the United Kingdom.

After screening almost 1000 publications, researchers selected 29 of the highest-quality randomized controlled trials. The studies compared true acupuncture with sham acupuncture (needling that did not penetrate the skin or needling at the wrong points) or no acupuncture (standard medical care) in almost 18,000 patients.

The authors carried out an individual patient data meta-analysis, which Dr Ahadian said was “unique” for this kind of research.

“Instead of 29 data points, they actually had almost 18,000 data points, so it was a much more powerful means of gathering data.”

The analysis showed that acupuncture was statistically superior to both sham acupuncture and nonacupuncture across several pain conditions, including neck and lower back pain, OA of the knee, headache, and migraine (all P for overall effect = .001).

The effect size for sham acupuncture was “a little bit smaller” than for nonacupuncture, said Dr Ahadian.

“That underscores the powerful effect of placebo that is associated with any type of physical modality, including acupuncture,” he said. He added that this presents “challenges for acupuncture research.”

The analysis also confirmed that acupuncture had “clinically meaningful effects, which is important,” said Dr Ahadian.

Clinically Meaningful Results

Other research has shown that acupuncture increases functional connectivity.

“Chronic pain can lead to abnormal patterns or disruption of functional connectivity in various brain centers,” explained Dr Ahadian. He added that acupuncture “can help modulate and help normalize” functional connectivity.

He pointed to another study  that included patients with moderate to severe knee OA who were acupuncture naive and had not had any interventions in the prior 6 months. Patients were randomly assigned to receive true acupuncture or sham acupuncture.

Each participant received six treatments over a 1-month period. They also underwent functional MRI.

Using the validated Knee injury and OA Outcome Score (KOOS), researchers found that the interaction between groups (real vs sham) and time (baseline vs endpoint) was significant for the KOOS subscale scores for pain (P = .025), function in sport (P = .049), and quality of life (P = .039).

The analysis demonstrated statistically significant improvement in functional connectivity in the right frontal parietal network and the executive control network, “which are the brain centers that are felt to play a significant role” in processing pain, said Dr Ahadian.

At the same time, there was decreased connectivity in the sensory motor network, he said. “These are patterns that you would expect with improved pain control.”

The results were clinically meaningful, noted Dr Ahadian. The study found that after treatment, the increase in functional connectivity was positively correlated with changes in KOOS pain scores.

In traditional Chinese medicine, pain and illness are believed to be caused by an obstruction to the normal flow of qi (vital energy). It might be that functional connectivity is correlated to qi, said Dr Ahadian.

“Could it be that when we talk about removing these obstructions, what we’re talking about is actually improving functional connectivity?”

Dr Ahadian stressed that finding effective alternative therapies to treat chronic pain is increasingly important in an era characterized by skyrocketing opioid-related deaths. In 2015, there were 33,091 such deaths in the United States, he said.

Another factor that should stimulate the search for effective pain therapies is the growing elderly population. The percentage of those aged 65 years and older was 13% in 2012 but is expected to rise to 20% by 2050. The incidence of chronic pain increases with age.

Training

In addressing a query from an audience member about training, Dr Ahadian referred him to the American Academy of Medical Acupuncture (AAMA), the professional society of physicians who have incorporated acupuncture into their medical practice.

According to the AAMA website, membership requirements have been established in accordance with training guidelines created by the World Health Organization–recognized World Federation of Acupuncture-Moxibustion Societies.

Other delegates were curious about the optimal number of acupuncture treatments and response times.

While some experts advise patients they need to try up to 20 treatments to know whether the treatment is working, “in my experience, if you don’t have some positive response within maybe 4 or 5 treatments, you may need to think twice,” said Dr Ahadian.

He noted that “not everybody is a great acupuncture responder.”

Certain factors may reduce a patient’s “acupuncture responsiveness. Acupuncture relies on an intact nervous system to cause its effect, so if patients have significant peripheral neuropathy, or other neuropathies, they may not be as responsive,” he said.

Once patients do respond, Dr Ahadian said he attempts to increase the interval between treatments while sustaining the results.

“Our goal in medicine is not to marry the patient to our office and have patients come in all the time,” he said.

“If I can’t get persistent efficacy, or reasonable efficacy, lasting a month, then I may advise against it or I may need to figure out how to change my therapy.”

In a keynote address elsewhere at the AIPM meeting, retired US Army Colonel Gregory D. Gadson, who lost both legs due to a roadside bomb blast while serving in Baghdad in 2007, and now suffers chronic pain, said he still receives occasional “battlefield acupuncture.”

When asked by Medscape Medical News about “battlefield acupuncture,” Dr Ahadian explained that it involves a brief session using small needles in the skin of the ear to block pain. The treatment can be administered in as little as 5 minutes and is being used to treat wounded US service members.

Dr Ahadian reports that he receives principal investigator research support from Boston Scientific and Mainstay Medical.

Academy of Integrative Pain Management (AIPM) 28th Annual Meeting. Presented October 22, 2017

#Poor evidence for efficacy of #cannabis in #chronic pain and #PTSD

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More research needed on benefits and harms of cannabis and plant-based cannabis products

Two new systematic evidence reviews have found limited evidence for the efficacy of cannabis and plant-based cannabis products in chronic pain and post traumatic stress disorder (PTSD).
The first review looked at 27 chronic pain trials, finding low-strength evidence for the benefits of cannabis in neuropathic pain, but insufficient evidence in other pain populations. Evidence is also limited on its association with an increased risk for nonserious short-term adverse effects and potentially serious mental health adverse effects, such as psychosis, the authors said.

A second review also found insufficient evidence regarding the benefits and harms of plant-based cannabis preparations in patients with PTSD. Observational studies had shown that compared with nonuse, cannabis did not reduce PTSD symptoms, the authors said. In addition, the studies had medium and high risk of bias. The authors noted, however, that several ongoing studies may soon provide important results.

In an accompanying editorial , Dr Sachin Patel from Vanderbilt Psychiatric Hospital in the US said the reviews “highlight an alarming lack of high-quality data from which to draw firm conclusions about the efficacy of cannabis for these conditions, for which cannabis is both sanctioned and commonly used.”
The reviews and editorial are published in the Annals of Internal Medicine. 

#Caffeine may serve as an opioid adjuvant in patients with #chronic pain

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Caffeine was associated with improvements in pain and other symptoms in patients with fibromyalgia-like chronic pain receiving opioids.

Caffeine may act as an opioid adjuvant in fibromyalgia-like chronic pain patients, new research suggests. The data, published in the Journal of Pain Research , suggest caffeine consumption concomitant with opioid analgesics could provide therapeutic benefits not seen with opioids alone.

Caffeine’s properties as an analgesic adjuvant with nonsteroidal anti-inflammatory drugs/paracetamol have already been documented. However, little clinical research has explored caffeine’s effects on opioid analgesia. This latest study assessed the effects of caffeine consumption on pain and other symptoms in 962 opioid-using and non-opioid-using patients with chronic pain.

In opioid users, caffeine consumption had modest but significant effects on pain, catastrophising, and physical function. Lower levels of pain interference were associated with low and moderate caffeine use compared to no caffeine intake. Lower pain catastrophising and higher physical function were observed in all caffeine dose groups relative to the no caffeine group. Lower pain severity and depression were observed only in the moderate caffeine group. In opioid non-users, low caffeine intake was associated with higher physical function; however, no other significant effects were observed.

The authors concluded that the absence of effects in opioid non-users suggests caffeine exhibits a weak but significant opioid analgesic adjuvant effect.

Novel Nondrug Approach May Help Chronic Pain

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Nancy A. Melville

PITTSBURGH — An innovative psychotherapeutic intervention involving the deconstruction of the emotional response to pain and the use of mindfulness to gain more control shows some efficacy as a nonpharmacologic approach to not only manage of chronic pain but also  reduce misuse of opioids.

The intervention, called mindfulness-oriented recovery enhancement (MORE), integrates aspects of mindfulness with other facets of psychotherapy, said its developer, Eric Garland, PhD, associate dean for research in the College of Social Work at the University of Utah, Salt Lake City, in presenting the research here at the American Pain Society (APS) 2017 Annual Scientific Meeting.

“MORE unites complementary aspects of mindfulness training, third-wave cognitive-behavioral therapy (CBT), and principles of positive psychology,” he said.

The therapy, detailed on Dr Garland’s website, specifically targets the hedonic dysregulation that occurs with addiction, stress, and chronic pain and focuses on three components: mindfulness, involving attentional control; reappraisal, involving psychological flexibility; and savoring, with a focus on reward processing.

Aspects of the approach specifically strive to deconstruct the emotional responses that can perpetuate and worsen chronic pain and to use visualization tools to gain perspective, Dr Garland said.

“Some chronic pain patients experience pain emotionally as an unchanging entity over which they lay a layer suffering, saying things like ‘Why me?’ and ‘This pain is ruining my life’.”

“We teach patients skills to remove the emotional overlay and to decompose the experience into subcomponent sensory sensations,” he said.

“For example, rather than experiencing the pain as this terrible anguish and emotional experience, we ask patients to focus on the pain as a cluster of sensations of heat, or tightness or tingling, as well as to pay attention to the spaces between such sensations, when there is no sensation at all.

“Coping with any one of the sensations may be more manageable than the monolithic experience of pain as a whole.”

Another session of the intervention involves focusing mindfully on a bouquet of flowers to generate and shift emotional reward from a natural reward as opposed to a drug-related source.

In a randomized, controlled trial of the intervention published in 2014, 115 patients with chronic pain for a mean of 10.4 years were randomly assigned to the MORE intervention or a standard support group for 8 weeks. Those in the MORE group showed significant reductions in pain severity.

Several recent studies have further demonstrated significant improvements in chronic pain associated with the intervention, including an indirect effect of reinterpretation of pain sensations and nonreactivity to aversive experiences, Dr Garland said.

“The studies showed the effects of MORE were driven by the capacity to reinterpret pain as innocuous sensory information as well as having nonreactivity to stressful thoughts and emotions,” he added

A subanalysis published this year in Drug and Alcohol Dependence using data from the study showed intriguing improvements in positive affect and reductions in misuse associated with the intervention.

The findings specifically showed greater improvements in measures of momentary pain (P = .01) and positive affect (P = .004) in the MORE group compared with the support group, and over the course of treatment, patients were significantly more likely to exhibit positive affect regulation (odds ratio, 2.75).

Additionally, improvements in positive affect (but not pain) during the intervention were associated with reduced risk of misusing opioids by post-treatment (P = .02).

Another analysis of the data, published in February in the Clinical Journal of Pain, showed a positive effect of MORE on deficits in hedonic capacity that can occur in chronic pain, characterized by increased sensitivity to aversive states and insensitivity to natural rewards.

In the analysis, dispositional mindfulness among those in the MORE group, assessed with the Five Facet Mindfulness Questionnaire, was associated with hedonic capacity scores, assessed on the Snaith-Hamilton Anhedonia and Pleasure Scale (P < .001).

“In light of this association, it is plausible that interventions that increase mindfulness may reduce pain-related impairment among opioid-using patients by enhancing hedonic capacity,” the authors conclude.

Dr Garland concluded that the MORE approach could have highly powerful effects.

“Teaching patients to ‘take in the good’ and mindfully savor natural, healthy pleasures may provide the learning signal needed to restore adaptive hedonic regulation and, ultimately, reverse addiction,” he said.

Dr Garland has disclosed no relevant financial relationships.

American Pain Society (APS) 2017 Annual Scientific Meeting.  Presented May 20, 2017.

 

Cannabis-based therapy shows promise in skin conditions

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A review of available evidence has concluded that cannabinoids could be useful in the treatment of eczema, psoriasis, and dermatitis.

Previous studies have investigated the use of cannabis-based therapy in areas such as chronic pain, nausea, and anorexia. A review of current literature has now determined that the anti-inflammatory properties of cannabinoids could make them useful in the treatment of a wide-range of skin diseases.

Writing in the Journl of the American Academy of Dermatologya , the authors said cannabinoids have a promising role in the treatment of itch. Studies to date have shown benefits with the use of cannabinoids in conditions such as pruritis, xerosis, prurigo and allergic dermatitis, to name but a few.

While the findings are promising, Dellavalle cautioned that most of these studies are based on laboratory models and large-scale clinical trials have not been performed before these therapies can be used for the management of dermatological conditions in practice. He said however, that for those who have used other medications for skin disease without success, trying a cannabinoid is a viable option.
“These diseases cause a lot of problems for people and have a direct impact on their quality of life,” he said. “The treatments are currently being bought over the internet and we need to educate dermatologists and patients about the potential uses of them.”

Chronic pain and rain: new link identified

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New study finds patients experience higher pain levels during wetter months.

Preliminary findings from a new study suggest a correlation between the weather and pain intensity in chronic pain sufferers.

The University of Manchester-led Cloudy with a Chance of Pain project collected data from more than 9,000 participants who recorded their daily pain symptoms on a smartphone app. The app correlated the data with real-time local weather events, using GPS.

At the halfway stage of the project, the team looked at data sets collected from participants in three cities; Leeds, Norwich and London. They found that in all three cities, as the number of sunny days increased from February to April, the amount of time patients reported they spent in severe pain decreased. The amount of time patients reported they experienced severe pain increased again when the weather was wetter and there were fewer hours of sunshine.

Will Dixon, Professor of Digital Epidemiology at The University of Manchester’s School of Biological Sciences and scientific lead for the Cloudy project, said the early results were “encouraging”.

The findings were presented at the British Science Festival this week.

Spinal cord stimulation reduces emotional response to chronic pain Stimulator alters connectivity and processing in specific brain regions associated with chronic pain.

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Stimulator alters connectivity and processing in specific brain regions associated with chronic pain.

Spinal cord stimulation may help relieve chronic pain. According to a study published in “Neuromodulation: Technology at the Neural Interface”, the stimulation reduces the emotional response to pain.

The study, carried out by Ohio State University (Columbus), was based on previous findings which showed that pain perception varies according to cognitive, emotional and sensory influences. Ten patients with chronic leg pain had a stimulator implanted in their spinal cord. Functional MRI was used to measure changes in their cortical networks.

The researchers found that stimulation can reduce the emotional connectivity and processing in certain areas of the brain. “Being able to modulate the connections between the brain areas involved in emotions and those linked to sensations may be an important mechanism involved in pain relief linked to spinal chord stimulation,” explained study leader Ali Rezai.

Using fMRI scans, it was possible to identify brain regions involved in pain perception and modulation. The researchers hope that by understanding more about neural networks they can develop new therapies to treat chronic pain.

Pain threshold raised by numbers of opiate receptors

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Study shows: adaptive response allowing people to deal with pain more easily.

The number of opiate receptors in the brain has a decisive influence on the pain threshold. A British study has shown that the number adapts to chronic pain in order to be better able to deal with pain. The study was published in “Pain”.

The study was carried out by Manchester University and included 17 patients with arthritis and nine healthy controls. Heat was applied to the participants’ skin using a laser simulator, and their brains were examined with Positron Emission Tomography (PET) to show the spread of opiate receptors dealing with the pain.

The more opiate receptors in the brain, the better the participants were able to cope with the pain, the researchers discovered. They also found that arthritis patients have more receptors. This suggests that the increase in opiate receptors in the brain is an adaptive response to chronic pain, enabling those affected to deal with it more easily.

“As far as we are aware, this is the first time that these changes have been associated with increased resilience to pain and shown to be adaptive,” said study author Christopher Brown. The underlying mechanisms are still unclear, but if one could find a way to enhance them, this may constitute a step towards naturally increasing resilience against pain without the adverse effects of painkillers, say the researchers.