Brainstem’s Role in Placebo and Pain Perception Highlighted

PainRelief.com Interview with:
Lewis Crawford, B.Sci (Hons), PhD Candidate 
Neural Imaging Laboratory | Faculty of Medicine and Health
University of Sydney 

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

Response: This study was performed as a means to accurately and robustly define the areas of the brainstem responsible for alleviating and enhancing pain via conditioning and expectation alone, that is, the phenomena of placebo analgesia and nocebo hyperalgesia. The reason we were able to do this was by being able to access a 7-tesla ultra-high field MRI, one of only two in Australia, that allowed us to resolve the small nuclei in the brainstem which make up descending analgesic circuitry (they carry signals from your brain to your spinal cord).

We found that a central pathway, comprised of the midbrain Periaqueductal Gray (PAG) and Rostral Ventromedial Medulla (RVM), acted during both phenomena, however in opposite ways. We also identified several other nuclei as playing a role in the modulation of pain which, prior to this study, had not been explored or suggested to play a role in this context. We believe that the brainstem circuitry we defined here enables further research into mechanisms responsible for analgesia and hyperalgesia and will promote further investigation into brainstem function in humans. 

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Astronauts Risk Herniated Discs and Back Pain From Space Flight

PainRelief.com Interview with:
Dr. Radostin Penchev
Johns Hopkins Medicine

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

Response: Although fewer than 600 people have travelled to space, human space travel is expected to exponentially surge with several companies now offering space excursions as well as with the establishment of the U.S. Space Force in 2019. In parallel with this effort, NASA plans to have a sustained presence on the Moon by 2028.

It turns out that more than 50% of astronauts experience back pain (termed space adaptation back pain) during their mission and are over 4 times more likely to suffer from herniated discs than the normal population. As such, physicians should anticipate a surge in space-related back pathology. More importantly, understanding the cause of back pain in astronauts may also improve the care for other austere environment populations including deep sea divers, fighter pilots and high-altitude explorers.

In this comprehensive review of the literature, we examined the epidemiology, potential causes, and treatments for spinal pain in astronauts.

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Tramadol Prescriptions for Pain Relief Linked to More Complications than Codeine

PainRelief.com Interview with:
Carlen Reyes PhD
Médico de familia
Gestora de proyectos de investigación IDIAP Jordi Gol

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

Response: Tramadol and codeine are two “weak” opioids frequently prescribed for different non-cancer pain indications, however, few are the studies that compare the adverse outcomes between them using large routinely collected primary care data. We aimed to fulfil this gap by analysing the risk of adverse events with the tramadol and codeine dispensations in a large primary care health care data (SIDIAP database) from Spain. 

We found that the dispensations of tramadol were associated with a greater risk of cardiovascular events, mortality and fractures compared to the dispensations of codeine. 

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Study Finds Medical Cannabis Not Likely to Solve Opioid Crisis for Pain Patients

PainRelief.com Interview with:
Carsten Hjorthøj, senior Researcher
Copenhagen Research Center for Mental Health – CORE, Mental Health Center Copenhagen, Copenhagen University Hospital
University of Copenhagen, Department of Public Health
Section of Epidemiology, Copenhagen, Denmark.

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

Response: Denmark introduced a pilot program of medical cannabis in 2018. Medical cannabis, and cannabis-based medicine, has gained a lot of both attention and controversy as a possible way to treat pain disorders, but the evidence base is still sparse. The Danish nationwide unselected registers allow us to perform a high quality pharmacoepidemiologic study with propensity score matched controls.

The main findings are that medical cannabis and cannabis-based medicine did not reduce the use of opioids in pain patients, and might actually lead to an increase in use of opioids. However, patients with neuropathic pain disorders appeared to reduce their use of gabapentin, their use of overall medication (but not opioids!), and the number of days spent in hospital, compared with controls.

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Chronic Migraine: TOP-PRO Study Compares Propranolol and Topiramate for Pain Relief

PainRelief.com Interview with:

Dr. Debashish Chowdhury
MBBS; DTCD; MD (Medicine); DM (Neurology); FIAN
Commonwealth Fellow in Stroke Medicine (Edinburg, UK)
Director – Professor and HOD
Department of Neurology, G B Pant Institute of Post Graduate Medical Education and Research,
New Delhi, India

Dr. Chowdhury

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

Response: Chronic migraine is a highly disabling headache disorder affecting about 2% of the global population. Oral preventive treatment options for chronic migraine are limited. Only topiramate has good evidence of efficacy. Although propranolol has class I evidence of efficacy for the prevention of episodic migraine, it has not been tested for chronic migraine with a robust clinical trial. Hence, we conducted an RCT, called the TOP-PRO study assessing the efficacy and tolerability of propranolol against topiramate for the prevention of chronic migraine using a non-inferiority design.

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Study Addresses How Weather Affects Pain Tolerance

PainRelief.com Interview with:
Erlend Hoftun Farbu, PhD student
Department of Community Medicine
The Arctic University of Norway
Tromsø, Norway

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

Response: Many report that weather affect their pain condition. Some studies confirm this, others do no. However, these studies have asked “How much pain do you have today?”

We used two tests to assess how much pain a person can tolerate. We then looked at how pain tolerance vary over time and if they are associated with weather.

The results show quite clearly that people can tolerate more pain caused by intense cold temperature in the colder months of the year. There was no such seasonal variation in pain caused by pressure to the leg. On the other hand, we found that both pressure pain tolerance and weather at one day was associated with the next days, but not the next month. When we further linked the weather and pain tolerance, we found that, for example, in some periods a rise in temperature happened at the same time as a rise in pain tolerance. While in other periods, there were no such association. We mean that this is because we adapt to the weather. For example, how we experience 5 °C (41°F) is different in autumn and spring..

Finally, temperature and barometric pressure could predict future values of pressure pain tolerance

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Acetaminophen (paracetamol) During Pregnancy May Alter Fetal Development

PainRelief.com Interview with:
Ann Z. Bauer ScD
Department of Work Environment
University of Massachusetts Lowell | UML 

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

Response: Acetaminophen (paracetamol, brand name Tylenol) is an over-the-counter medication used to relieve pain and reduce fever. It is an active ingredient in over 600 medications and used by more than 50% of pregnant women worldwide and up to 65% of pregnant women in the US.

Current guidance recommends acetaminophen as the pain reliever of choice during pregnancy, as other pain relievers such as ibuprofen and aspirin are contraindicated during pregnancy, particularly after 20 weeks.

In this consensus statement the authors reviewed the research on acetaminophen use during pregnancy from 1995 through 2020 and found a growing body of evidence that suggests prenatal acetaminophen exposure may alter fetal development increasing the risk of neurodevelopmental, reproductive and urogenital disorders. Importantly, this review identifies a convergence of evidence from the trifecta of research areas -human cohort studies, in vitro and animal models. This statement asking for precaution and more research was supported by a total of 91 clinicians and researchers (13 authors and 78 signatories) from around the world.

Research suggests acetaminophen is an endocrine disruptor meaning it interferes with the proper functioning of hormones, specifically it is an anti-androgen that can significantly reduce testosterone production.  Acetaminophen exposure during pregnancy has been suggested to increase the risk of male undescended testicles (cryptorchidism) and shorter anogenital distance (ADG) a marker of sub-fertility.  Additionally, research suggests increased risk of neurodevelopmental disorders primarily attention deficit hyperactivity disorder (ADHD) and related behavioral abnormalities, but also autism spectrum disorder (ASD), language delays, decreased IQ, and conduct disorders.

Many users do not consider acetaminophen to be a medication with potential side effects. There is high usage, in part, because of a perception  that use is of negligible risk.  However, because use is so common, if acetaminophen is responsible for even a small increase in individual risk it could contribute substantially to these disorders in the overall population.

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Migraine Pain Linked to Stress Varies by Individual

PainRelief.com Interview with:

Serena L. Orr, MD, MSc, FRCPC, FAHS
Assistant Professor
Depts of Pediatrics, Clinical Neurosciences and Community Health Sciences 
Cumming School of Medicine, University of Calgary
Director, Pediatric Headache Program
Alberta Children’s Hospital

Dr. Orr

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

Response: Stress has long been felt to be one of the most common trigger factors for migraine. However, there is very little data on the relationship between stress and pain severity in individuals with migraine on a day-to-day basis, and this relationship is even more poorly understood among individuals with more frequent attacks, such as those with chronic migraine (who have at least 15 days/month of headache, 8 or more of which meet criteria for migraine attacks).

This was a study that looked at daily electronic headache diary data for 136 adults with chronic migraine, using data from the N1-Headache application. In this study, we aimed to understand the relationship between perceived stress and pain severity in individuals with chronic migraine. Individuals completed 90 days of daily diary entries where they reported on their headache characteristics, and their perceived stress levels, measured on a scale of 0-10.

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Caution Should Be Taken with Hip Steroid Injections For Arthritis Pain Relief

PainRelief.com Interview with:
Kanu M. Okike, MD
Orthopedic Surgeon
The Hawaii Permanente Medical Group

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

Response: Hip corticosteroid injections are a common treatment for osteoarthritis and other hip conditions.  Recently, isolated case reports have raised the question of whether hip corticosteroid injections could be associated with rapid progression of the arthritis process – a condition known as rapidly destructive hip disease (RDHD).

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Pain Relief Study of Low Carb Ketogenic Diet

PainRelief.com Interview with:
Rowena Field

B.App.Sc (phty) M.Physio. APAM
Physiotherapist/Director
PhD research candidate Sydney University
STEPP (solutions tools and education for persistent pain)

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

Response: Chronic pain is a difficult problem to treat because it is multifactorial, driven by the brain continuing to arrive at the conclusion that protection is required. Turning up the sensitivity in the nervous system results in ongoing pain as a protector even though there is no new tissue damage. Other protection mechanisms such as increased inflammation, and increased sympathetic ‘fight or flight’ also occur.

Chronic pain becomes part of a whole system protective response, so looking at other treatment options that alter the system (such as diet) are useful additions to pain management. A ketogenic diet restricts carbohydrate to below 50g/day producing ketones for energy from fat. It has been used to treat epilepsy over the last two centuries and successfully reduces nervous system excitability. Many of the drugs used for chronic pain (such as Lyrica) are also anti-epileptic medications, suggesting common pathways. As well as these impacts on the nervous system, pre-clinical research has also shown ketones to be signalling molecules that reduce inflammation.

Combined with the clinical reports that pain reduction occurred when people were on ketogenic diets, it seemed reasonable to test the diet specifically in a chronic pain population.

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