Pain Suppresses the Activity Of the Brain Reward System

Stéphane Potvin, PhD
Centre de recherche
Institut Universitaire en Santé Mentale de Montréal
Full professor; Department of psychiatry and addiction
University of Montreal

PainRelief.com: What is the background for this study? What are the main findings?

Dr. Potvin: Let’s begin by using a concrete example. First, imagine that you are taking a walk and it is really cold outside; so cold, in fact, that you can no longer enjoy the experience. Upon returning home, you realize that you no longer feel the pain, and you now have a smile on your face. During this sequence of events, what happened in your brain? To figure it out, we performed a functional neuroimaging study during which a painful cold gel was applied on the right foot of a group of healthy volunteers. What we discovered is that during pain stimulation, there was a clear de-activation of the medial orbito-frontal cortex, which is one of the main “pleasure” centers in the brain. Intriguingly, we observed that after the cold pain stimulation was discontinued, participants experienced significant levels of pleasant emotions that lasted for approximately 4 minutes.

Opioid Analgesic Use For Pain Relief in Chronic Noncancer Pain

PainRelief.com Interview with:
Dr Stephanie Mathieson
NHMRC Health Professional Research Early Career Fellow
The University of Sydney
Faculty of Medicine and Health, Sydney School of Public Health
Institute for Musculoskeletal Health
Royal Prince Alfred Hospital Australia

PainRelief.com:  What is the background for this study?

Response: Chronic non-cancer pain, such as chronic non-specific low back pain has a substantial impact on society by costing billions of dollars each year in health care costs and lost productivity.

Current clinical practice guidelines for the management of chronic non-cancer pain, such as those from the Centers for Disease Control and Prevention, now recommend avoiding the initial use of opioid analgesics, as the risk of harms, such as overdose and death.

We wanted to establish the extent to which opioid analgesics are used by people with chronic noncancer pain. This is important, as many studies report how many opioids are prescribed, but this may not represent the actual use of opioid analgesics.

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Stronger Pain Relief When Patient and Provider Demonstrate Facial Mirroring

PainRelief.com Interview with:
Dan-Mikael Ellingsen PhD
Department of Psychology, University of Oslo
Norwegian Centre for Mental Disorders Research (NORMENT),
Division of Mental Health and Addiction
Oslo University Hospital, Oslo, Norway.

Dr. Ellingsen

PainRelief.com:  What is the background for this study?  What are the main findings?

Response: We know that the patient-clinician relationship can have an important impact on clinical outcomes, but we know relatively little about how this works. A better understanding of the behavioral, physiological, and brain mechanisms behind the patient-clinician interaction may help demystifying the therapeutic relationship and how it influences treatment outcomes.

In order to investigate the behavioral and brain mechanisms involved when patients and clinicians interact, we simultaneously recorded brain activity (using functional MRI) in clinicians and patients with chronic pain, while they underwent a pain treatment session. We also recorded and analyzed non-verbal communication – facial expressions – during the interaction. We found that when the patient and clinician had first established a level of rapport – or therapeutic alliance – through a clinical intake and consultation, they showed stronger concordance in brain activity in brain areas involved in empathy and “theory of mind” (the process of trying to understand other people’s mental states) when they engaged during treatment. We also found that in interactions where the patient and clinician showed more mirroring in facial expressions, the patient also reported higher therapeutic alliance and stronger pain relief from the treatment.

High Dose Pain Reliever Paracetamol -Acetaminophen Linked to Increase in Overdoses

PainRelief.com Interview with:
Andrea Burden, Ph.D.
Assistant Professor of Pharmacoepidemiology
Institute of Pharmaceutical Sciences
Zurich Switzerland

PainRelief.com:  What is the background for this study?

Response: Paracetamol (also known as acetaminophen) is one of the most commonly used medications in the world. While the drug is generally safe, daily intake exceeding 4,000 milligrams (4 grams) can lead to irreversible liver injury and even death. Traditionally in Europe, paracetamol is available in two dose formulations, the 500 and 1,000 milligram tablets. The lower dose formulation is often available over-the-counter (without a prescription), while the high-dose formulation requires a medical prescription. In the last decade, there has been accumulating evidence that both the availability of high-doses of paracetamol, and the quantity of paracetamol available to patients, are associated with the risk of overdose. Therefore, in this study, we aimed to identify if there was an increase in the number of calls to the National Poison Information Centre in Switzerland for paracetamol-related overdoses after the high-dose 1,000 milligram (1 gram) paracetamol tablets became available in October of 2003. We also examined if there were differences in the circumstances of the overdose and severity between the 500 milligram or 1,000 milligram tablets.

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Can CBD and Cannabis Provide Pain Relief in Fibromyalgia?

PainRelief.com Interview with:
Amnon A. Berger, MD, PhD
MD/PhD Program 2006-2017
The Hebrew University Hadassah Medical School
Jerusalem, Israel
Resident Physician (CA-1/PGY-2) and Loring Scholar
Department of Anesthesiology, Critical Care and Pain Medicine
Beth Israel Deaconess Medical Center, Boston, MA

Dr. Berger

PainRelief.com:  What is the background for this study?  What are the main findings?

Response: Fibromyalgia is a common disorder of chronic widespread pain. It has been estimated to affect 2-4% of the general population, though that number is likely an underestimate of the actual incidence. Outside of chronic pain, it also contributes to morbidity and disability because it affects sleep, causes cognitive impairment and psychiatric perturbations. Fibromyalgia is difficult to diagnose and even more difficult to treat.

Because the underlying causes – the etiology and pathophysiology at the base of this condition – are still largely unknown, it is harder to tailor specific treatments. There is evidence to support several modes of treatment, but truly high-level evidence exists only for physical exercise. Effective treatment depends on long term commitment and a multimodal approach by a multidisciplinary team.

Recently, with the rise of use in cannabis and CBD, both for medical and recreational use, evidence has emerged to support its use in fibromyalgia. While most of the evidence is not clear cut and not high enough evidence to support cannabis use, the evidence is overall positive and cannabis derivatives may be an effective choice as part of a multimodal treatment plan.

FDA Recommends Avoiding NSAIDs for Pain Relief in Pregnancy at 20 Weeks or Later

MedicalResearch.com Interview with:
Catherine Y. Chew, PharmD, BCGP

Deputy Director, Division of Drug Information
Center for Drug Evaluation and Research
U.S. Food and Drug Administration

Catherine Y. Chew, PharmD, BCGP Deputy Director, Division of Drug Information Center for Drug Evaluation and Research U.S. Food and Drug Administration
Dr. Chew

MedicalResearch.com:  What actions is FDA taking regarding NSAID use during pregnancy?

Response: The U.S. Food and Drug Administration (FDA) is warning that use of prescription or over-the-counter (OTC) nonsteroidal anti-inflammatory drugs (NSAIDs) from around 20 weeks of pregnancy through the end of pregnancy may cause rare but serious kidney problems in an unborn baby. This can lead to low levels of amniotic fluid surrounding the unborn baby and possible complications.

For prescription NSAIDs, FDA is requiring changes to the prescribing information to describe the risk of kidney problems in unborn babies; these kidney problems can result in low amniotic fluid. FDA is recommending that pregnant women avoid NSAIDs from around 20 weeks of pregnancy. Prescribing information already recommends avoiding NSAIDs from around 30 weeks through the end of pregnancy because NSAIDs can cause a problem that may result in heart issues in the unborn baby. If NSAID use is necessary between 20 and 30 weeks of pregnancy, NSAID use should be limited to the lowest effective dose for the shortest possible duration. Health care professionals should consider ultrasound monitoring of amniotic fluid if a pregnant woman uses NSAIDs beyond 48 hours.

FDA will also work with sponsors to request updates of the Drug Facts labels of OTC NSAIDs intended for use in adults. These labels already warn to avoid using NSAIDs during the last three months of pregnancy because the medicines may cause problems in the unborn baby or complications during delivery. The Drug Facts labels also already advise pregnant and breastfeeding women to ask a health care professional before using these medicines.

MedicalResearch.com: What did FDA find?

Response: These labeling changes are based on cases reported to FDA about low amniotic fluid levels or kidney problems in unborn babies associated with NSAID use during pregnancy. FDA’s medical literature review also contributed to the basis for the labeling changes.

Among the 35 cases of low amniotic fluid levels or kidney problems reported to FDA through 2017, all were serious. Two newborns who died had kidney failure and confirmed low amniotic fluid when mothers took NSAIDs while pregnant; three other newborns who died had kidney failure without confirmed low amniotic fluid when mothers took NSAIDs while pregnant. The low amniotic fluid levels started as early as 20 weeks of pregnancy. In 11 cases where low amniotic fluid levels were detected during pregnancy, the fluid volume returned to normal after the woman stopped taking the NSAID.

FDA’s medical literature review yielded similar findings. In these publications, low amniotic fluid levels were detected with NSAID use for varying amounts of time, ranging from 48 hours to multiple weeks. In most cases, the condition was reversible within three to six days after stopping the NSAID. In many reports, the condition was reversed when the NSAID was stopped; the condition reappeared when the same NSAID was started again.

MedicalResearch.com: What are NSAIDs? Are all NSAIDs included in the new FDA recommendations to avoid NSAID use from around 20 weeks through the end of pregnancy?

Response: For decades, people have used NSAIDs to treat pain and fever from many different long- and short-term medical conditions, such as arthritis, menstrual cramps, headaches, colds, and the flu. NSAIDs work by blocking the production of certain chemicals in the body that cause inflammation. There are both prescription and OTC NSAIDs.

NSAIDs are available alone and combined with other medicines for the temporary relief of pain and fever, including pain or fever symptoms associated with colds, flu, and insomnia. Examples of NSAIDs include ibuprofen (Advil, Motrin), naproxen (Aleve), diclofenac (Voltaren), and celecoxib (Celebrex) and aspirin.

An exception to these new FDA recommendations is the use of the low-dose aspirin (81 mg) for certain pregnancy-related conditions at any point in pregnancy under the direction of a health care professional. Low-dose aspirin may be an important treatment for some women during pregnancy. The recommendations also do not apply to NSAIDs administered directly to the eye.

MedicalResearch.com: NSAIDs already carry a warning about use in late pregnancy. What is different about these labeling changes?

Response: Warnings to avoid taking NSAIDs after about 30 weeks of pregnancy are already included in the prescribing information because taking these medications during this time may lead to heart issues in the unborn baby. The new labeling changes recommend avoiding NSAIDs as early as about 20 weeks of pregnancy because of the risk of kidney problems that result in low amniotic fluid.

MedicalResearch.com: What should pregnant women and health care professionals do? What are other options for pain relief during pregnancy?

Response: Women should not use NSAIDs after around 20 weeks in pregnancy unless specifically advised to do so by a health care professional. Because many OTC medicines contain NSAIDs, pregnant women should read the Drug Facts labels to determine if the medicines contain an NSAID. If pregnant women are unsure if a medicine contains an NSAID, they should ask a pharmacist or health care professional for help.

Other medicines, such as acetaminophen (Tylenol), are available to treat pain and fever during pregnancy. Pregnant women should ask their pharmacist or health care professional for help deciding which medication might be best.

Health care professionals should limit prescribing NSAIDs between 20 to 30 weeks of pregnancy and avoid prescribing them after 30 weeks of pregnancy. If NSAID treatment is determined necessary, health care professionals should limit use to the lowest effective dose and shortest duration possible. They should also consider ultrasound monitoring of amniotic fluid if the pregnant woman regularly uses NSAIDs longer than 48 hours and discontinue the NSAID if low amniotic fluid levels are found.

Citation:

FDA recommends avoiding use of NSAIDs in pregnancy at 20 weeks or later because they can result in low amniotic fluid
NSAIDs may cause rare kidney problems in unborn babies

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Traditional and Battlefield Acupuncture Provide Post-Op Pain Relief and Reduced Need for Opioids

PainRelief.com Interview with:

  • Brinda Krish, D.O., lead author of the study and an anesthesiology resident at Detroit Medical Center.
  • Padmavathi Patel, M.D., principal investigator of the study and Medical Director, Northstar Anesthesia at John D. Dingell Veteran Hospital.

PainRelief.com:  What is the background for this study?  What are the main findings?

Dr. Padmavathi Patel: Pain is a major contributor to health care costs and a common cause of long-term disability (about  $61.2 billion/year) in lost productivity due to pain.

acupuncture

76.2 million Americans (one in four) have suffered from pain that lasts longer than 24 hours (2013).

Numerous literature such as:

1. “Use of prescription opioids in the treatment of pain has increased notably over recent decades.”

2. “Rates of death from prescribed opioids increased four fold between 2000 and 2014.”

3. “16,651 opioid related deaths in 2010.”

4. “The problem of opioid overuse and dependence is seen in the military as well as in civilian.”

-Opioid-related side effects could lead to a delay in recovery.
-Pain control is more challenging for military population.
-More extensive injuries and greater pain severity is seen in survivors of combat- related blast injuries compared to those of non-blast civilians and also they require larger opioid doses.
-Pain is a very common patient complaint, both in veteran and non-veteran populations.
-Among the 5.7 million unique patients seen annually with in the Department of Veterans Affairs (DVA), more than half of these patients experience chronic pain.

In 2017, The DVA and the United States Department of Defense (DoD) published an updated guidelines on opioid therapy for chronic pain that strongly recommends against initiation of long-term opioid use and recommends alternatives, including non-pharmacologic therapy, such as Acupuncture, which has been shown to be effective for treating a variety of painful conditions.

Acupuncture techniques have been in existence for centuries, with roots tied to Eastern Asia. Traditional acupuncture involves the insertion of very thin needles at specific trigger points around the body to relieve pain. Battlefield acupuncture (BFA), developed by a U.S. Air Force doctor uses needles that are inserted at various trigger points in the ear. In 2013, $5.4 million was awarded to the Departments of Defense and Veterans Affairs to teach BFA to healthcare providers in both the military and the Department of Veterans Affairs and assess it.  In light of the opioid epidemic, there is a strong need to decrease perioperative opioid use. Opioid use due to postoperative pain along with perioperative anxiety has been linked to increased length of hospital stay, increased morbidity and mortality, and ultimately higher healthcare costs.

Battlefield acupuncture was introduced into Veterans Health Administration (VHA) in the last few years and in VHA, clinicians of various disciplines (MDs, DOs, PAs, nurse-practitioners), can currently obtain clinical privilege to provide it.

I received the Battlefield acupuncture training at John D. Dingell VA medical Center, Detroit and I was surprised with the outcomes of chronic pain patients. As an anesthesiologist I know pain after the surgery is common, often severe and largely unnecessary. I discussed these concerns with the surgeons and created the protocol to use BFA for general surgical patients and traditional acupuncture for hip replacement patients as an adjuvant to the standard protocol for acute post-surgical pain control.

Effective relief of postoperative pain is vital. Such pain probably prolongs hospital stay, as it can affect all the organ systems with side effects. Post op pain remains grossly under treated, with up to 70% of patients reporting moderate to severe pain following surgery.

Multimodal pain control not only can result in earlier discharge from hospital, but it may also reduce the onset of chronic pain syndromes.

2 studies performed TA (n=21), Controls given sham acupuncture (n=21).  BFA (n=28), Controls given sham acupuncture (n=36). Measured variables included post-operative opioid requirements, postoperative pain, the incidence of PONV, and patient satisfaction scores

Key conclusions use of Battlefield acupuncture and Traditional acupuncture reduced post-operative opioid requirements, post-operative pain scores (pain intensity) and increased patient satisfaction scores.  BFA also reduced PONV in patients.  

Opioid Epidemic for Pain Relief Has Waned But is Not Over

PainRelief.com Interview with:
Mario Moric M.S.
Department of Anesthesiology
Rush University Medical
Center Department of Anesthesiology

PainRelief.com:  What is the background for this study?  What are the main findings?

  • Prescription Pain Medicine (PPM) abuse has become a national problem and is now consider an epidemic. In 2012, health care providers wrote 259 million prescriptions for opioid pain medication; enough for every American adult to have a bottle of opioids. 
  • With the recent public information campaign about the epidemic and the possible addictive nature of opioid prescription pain medications, the abuse rates have declined.  We examined data from the National Survey on Drug Use and Health (NSDUH) public data derived from a national survey. 
  • We have raw data (actual reported rates of PPM abuse, see attached image) and weighted data (corrected for the sampling design).  Looking at the raw data you can see that abuse rates for lifetime use (highest line), past year use (middle red line) and past month use (bottom green line) are all more or less stable until 1998 after which we saw huge increase. From 1998 to 2004 the lifetime use increased 186%, the past year use increased 193% and the past month use increased 183%.  Then the decrease, from 2009 to 2018 the lifetime use decreased 72%, the past year use decreased 90% and the past month use decreased 185%.
  • Using the weighted data, the past year use decreases 26% and was statistically significant, indicating a real world decrease in prescription pain medication abuse.
Prescription Pain Medicine

COVID-19 Protein Provides Pain Relief, Opening Up Targets for Future Pain Treatments

PainRelief.com Interview with:
Rajesh Khanna, PhD
Professor of Pharmacology, Anesthesiology and Neuroscience
University of Arizona 
Tucson, AZ 85724

PainRelief.com:  What is the background for this study?

Response: SARS-COV-2 infection can be spread by asymptomatic, presymptomatic, and symptomatic carriers. Transmission of SARS-CoV-2 by asymptomatic or presymptomatic individuals may account for half of the spread, which may be why the virus has been so difficult to contain. The data from our study shows that the Spike protein, the major surface antigen of SARS-CoV-2, is analgesic. Therefore, an explanation for the unabated spread may be that asymptomatic or presymptomatic individuals do not experience the pain and discomfort that act as early warning signs of infection.

How Do Primary Care Physicians Handle Opioids For Patients Seeking Chronic Pain Relief?

PainRelief.com Interview with:
Laura Militello
Unveil, LLC
Applied Decision Science, LLC

PainRelief.com:  What is the background for this study?

Response: Little is known about how primary care clinicians’ (PCC) approach chronic pain management in the current climate of rapidly changing guidelines and the growing body of research about risks and benefits of opioid therapy. When it comes to pain management, primary care clinicians (PCCs) find themselves in a somewhat unexpected role. Few conditions intersect with a range of specialties (i.e. mental health, orthopedics, endocrinology, etc.), disability, and aberrant behavior in the way that chronic pain does. PCCs find themselves in a position where they are asked to assess and diagnose sometimes vague and diffuse pain, and determine appropriate treatment often before the underlying cause of the pain is well-understood.

A recent cultural shift in the U.S. has created a situation in which a formerly default treatment, prescription opioid therapy, is no longer considered safe or appropriate for many patients with chronic pain. The addictive qualities and overall safety profile of opioid medications have come into sharp focus in recent years, leading to a push to reduce opioid use while also trying to achieve pain relief with little guidance for PCCs about how to manage this change in treatment plans. Others have documented the uneasiness many experience in managing patients with chronic pain. One participant in our study described the sense that opioid prescribing sometimes extends into unexpected and disconcerting territory in this way: “I never signed up to be an enforcer.” The complexity and moral uncertainty (6) associated with managing patients with chronic pain is an important backdrop for the findings from this study.