A new study cites a possible breakthrough treatment in pain management

Pain in children


Damaged nerves can be regenerated with the application of a frozen needle under advanced imaging guidance, according to new research to be presented at the Society of Interventional Radiology Annual Scientific Meeting in Boston.

The technique, called interventional cryoneurolysis, is performed by an interventional radiologist and can offer hope to patients in persistent pain following a traumatic injury.

“The idea that we can induce regeneration of damaged nerves simply by placing a cold needle through the skin under imaging guidance is extremely exciting,” said the lead author of the study, J. David Prologo, MD, FSIR, ABOM-D, an interventional radiologist and associate professor at Emory University School of Medicine in Atlanta. “This research answers the call from United States legislators and specialty medical societies to develop alternatives to opioids for the management of pain.”

Researchers at Emory University treated eight patients with chronic nerve pain related to a prior trauma with CT-guided interventional cryoneurolysis. CT-guided cryoneurolysis uses imaging to place a needle and freeze damaged nerves, causing them to degenerate and lose function. “What happens next is almost magical,” Prologo says. “If the nerve is exposed to the correct amount of cold, over the correct area, for the right amount of time, it will regenerate—replacing the previously damaged nerve with a healthy one.” 

In this study, the average time from traumatic injury to the procedure was 9.5 years. There were no procedure related complications or adverse events, and all patients returned to their baseline strength over time—confirming regeneration of the targeted nerve. In six of the eight patients, pain symptoms dramatically improved following regeneration—reflected as a collective decrease of 4.6 points in Visual Analog Scale pain scores.

Prologo believes that the interventional radiology skillset applied to nerve freezing has many applications for treatment of complex pain. “We are using this regeneration technique not only to manage nerve pain induced by trauma—but also for pudendal neuralgia, post mastectomy pain, post-surgical pain, and many other conditions historically managed with narcotics,” says Prologo. “Interventional radiologists can place these needles safely in precise locations all over the body, allowing access to pain generators that were previously unreachable and giving hope to patients who struggle with pain.”

Cannabis-related products demonstrate a short-term reduction in chronic pain


The evidence behind the effectiveness of cannabis-related products to treat chronic pain is surprisingly thin, according to a new systematic evidence review by researchers at Oregon Health & Science University.

The federally funded review, which will be updated on an ongoing basis, was published today in the Annals of Internal Medicine.

Researchers did find evidence to support a short-term benefit in treating neuropathic pain – caused by damage to peripheral nerves, such as diabetic neuropathy resulting in pain described as burning and tingling, involving two FDA-approved synthetic products with 100% tetrahydrocannabinol, or THC: dronabinol (under the trade name Marinol) and nabilone (Cesamet). Both products also lead to notable side effects including sedation and dizziness, according to the review.

Another product, a sublingual spray of equal parts THC and cannabidiol, or CBD, extracted from the cannabis plant, known as nabiximols, also showed evidence of some clinical benefit for neuropathic pain, although that product is not available in the U.S. This product also led to side effects, such as nausea, sedation and dizziness.

“In general, the limited amount of evidence surprised all of us,” said lead author Marian S. McDonagh, Pharm.D., emeritus professor of medical informatics and clinical epidemiology in the OHSU School of Medicine. “With so much buzz around cannabis-related products, and the easy availability of recreational and medical marijuana in many states, consumers and patients might assume there would be more evidence about the benefits and side effects.

“Unfortunately, there is very little scientifically valid research into most of these products,” she said. “We saw only a small group of observational cohort studies on cannabis products that would be easily available in states that allow it, and these were not designed to answer the important questions on treating chronic pain.”

Voters in Oregon, Washington and 20 other states have legalized medical and recreational marijuana, however, the researchers found many of the products now available at U.S. dispensaries have not been well studied.

“For some cannabis products, such as whole-plant products, the data are sparse with imprecise estimates of effect and studies had methodological limitations,” the authors write.

This situation makes it difficult to guide patients.

“Cannabis products vary quite a bit in terms of their chemical composition, and this could have important effects in terms of benefits and harm to patients,” said co-author Roger Chou, M.D., director of OHSU’s Pacific Northwest Evidence-based Practice Center. “That makes it tough for patients and clinicians since the evidence for one cannabis-based product may not be the same for another.”

The living review, including a visual abstract summary of the findings, will also be shared on a new web-based tool launched by OHSU and VA Portland Health Care System early this year to help clinicians and researchers evaluate the latest evidence around the health effects of cannabis. Known as Systematically Testing the Evidence on Marijuana, or STEM, the project includes “clinician briefs” to help health care workers translate the clinical implications.

“This new living evidence review is exactly the type of resource clinicians need to clarify for patients the areas of potential promise, the cannabis formulations that have been studied and, importantly, the major gaps in knowledge,” said co-author Devan Kansagara, M.D., M.C.R., professor of medicine in the OHSU School of Medicine and a staff physician at the VA Portland.

Reviewers searched more than 3,000 studies in the scientific literature as of January of this year and landed on a total of 25 with scientifically valid evidence – 18 randomized controlled studies and seven observational studies of at least four weeks.

The effects of cannabis and related products are based on their ability to mimic the body’s own endocannabinoid system. The system is comprised of receptors and enzymes in the nervous system that regulate bodily functions and can affect the sensation of pain.  In the evidence review, researchers sorted the types of product into high, comparable and low ratios of THC to CBD and compared their reported benefits and side effects.

Dronabinol and nabilone fit into the high THC to CBD ratio category, with 100% THC (no CBD), showing   the most benefit among the products studied, with meta-analysis of the six randomized controlled studies demonstrating statistically valid benefits for easing neuropathic pain compared to a placebo.

“Honestly, the best advice is to talk to your primary care physician about possible treatments for chronic pain,” McDonagh said. “If you want to consider cannabis, you need to talk to your doctor.”

How pain is generated in the brain explored in cutting-edge study

Isochronic music to help ease chronic pain, headaches, or sleep.

A state-of-the-art University of Essex study has developed a new scientific approach to understanding how pain is generated in the brain. 

The research led by Dr Elia Valentini focused on studying a potential indicator of pain – the oscillation in the alpha band.

These important brain waves fall in the middle of the spectrum and are generated as people take on day-to-day tasks. 


Dr Valentini developed a new method of studying how these waves change under stress and pain. 

As part of the study, 36 healthy volunteers were tested with an electroencephalogram (EEG) and electrical brain activity was recorded from different parts of their heads. 

They had five-minute sessions of rest, painful hot water immersion, warm water and an unpleasant sound listening. 

By studying brainwaves the team was able to pinpoint differences between heat, pain, and unpleasant sound. 

Dr Valentini and his colleagues identified specific parts of the head where the alpha waves slowed down during pain. 

Dr Valentini, from the Department of Psychology, said: “We made a critical study that addressed the important issue of sensitivity and specificity of pain biomarkers, which is a crucial methodological question to develop novel treatment for people suffering from chronic pain.” 

The research and advanced data analysis allowed the team to produce an accurate picture of alpha oscillations during pain. 

It is hoped the study – published in NeuroImage – will pave the way for further research which could lead to a better understanding of how pain is generated within the brain. 

Dr Valentini now hopes to expand upon this research with even more advanced data analysis and experiments – to discover more about alpha waves and pain. 

Pain and Inflammation – The science of acupuncture

The science of acupuncture
The science of acupuncture

Acupuncture is a traditional Chinese technique that has been used for millennia to treat chronic pain and other health problems associated with inflammation, yet the scientific basis of the technique remains poorly understood. 

Now, a team of researchers led by neuroscientists at Harvard Medical School has elucidated the underlying neuroanatomy of acupuncture that activa

In a study conducted in mice and published Oct. 13 in Nature, the team identified a subset of neurons that must be present for acupuncture to trigger an anti-inflammatory response via this signaling pathway. 

The scientists determined that these neurons occur only in a specific area of the hindlimb region—thus explaining why acupuncture in the hindlimb works, while acupuncture in the abdomen does not. 

“This study touches on one of the most fundamental questions in the acupuncture field: What is the neuroanatomical basis for body region, or acupoint, selectivity?” said lead investigator Qiufu Ma, HMS professor of neurobiology at Dana-Farber Cancer Institute.

One area of particular interest to the research team is the so-called cytokine storm—the rapid release of large quantities of cytokines that frequently drives severe, systemic inflammation, and can be triggered by many things, including COVID-19, cancer treatment, or sepsis. 

“This exuberant immune response is a major medical problem with a very high fatality rate of 15 percent to 30 percent,” Ma said. Even so, drugs to treat cytokine storm are lacking. 

Adapting an ancient technique to treat aberrant inflammation

In recent decades, acupuncture has been increasingly embraced in Western medicine as a potential treatment for inflammation. 

In this technique, acupoints on the body’s surface are mechanically stimulated, triggering nerve signaling that affects the function of other parts of the body, including organs. 

In a 2014 study, researchers reported that electroacupuncture, a modern version of traditional acupuncture that uses electrical stimulation, could reduce cytokine storm in mice by activating the vagal-adrenal axis—a pathway wherein the vagus nerve signals the adrenal glands to release dopamine. 

In a study published in 2020, Ma and his team discovered that this electroacupuncture effect was region specific: It was effective when given in the hindlimb region, but did not have an effect when administered in the abdominal region. The team hypothesized that there may be sensory neurons unique to the hindlimb region responsible for this difference in response. 

In their new study, the researchers conducted a series of experiments in mice to investigate this hypothesis. First, they identified a small subset of sensory neurons marked by expression of the PROKR2Cre receptor. They determined that these neurons were three to four times more numerous in the deep fascia tissue of the hindlimb than in the fascia of the abdomen. 

Then the team created mice that were missing these sensory neurons. They found that electroacupuncture in the hindlimb did not activate the vagal-adrenal axis in these mice. In another experiment, the team used light-based stimulation to directly target these sensory neurons in the deep fascia of the hindlimb. 

This stimulation activated the vagal-adrenal axis in a manner similar to electroacupuncture. “Basically, the activation of these neurons is both necessary and sufficient to activate this vagal-adrenal axis,” Ma said. 

In a final experiment, the scientists explored the distribution of the neurons in the hindlimb. They discovered that there are considerably more neurons in the anterior muscles of the hindlimb than in the posterior muscles, resulting in a stronger response to electroacupuncture in the anterior region. 

“Based on this nerve fiber distribution, we can almost precisely predict where electrical stimulation will be effective and where it will not be effective,” Ma explained. 

Together, these results provide “the first concrete, neuroanatomic explanation for acupoint selectivity and specificity,” Ma added. “They tell us the acupuncture parameters, so where to go, how deep to go, how strong the intensity should be.” 

He noted that while the study was done in mice, the basic organization of neurons is likely evolutionarily conserved across mammals, including humans. 

However, an important next step will be clinical testing of electroacupuncture in humans with inflammation caused by real-world infections such as COVID-19. Ma is also interested in exploring other signaling pathways that could be stimulated by acupuncture to treat conditions that cause excessive inflammation. 

“We have a lot of tough chronic diseases that still need better treatments,” he said, such as inflammatory bowel syndrome and arthritis. Another area of need, he added, is excessive immune reactions that can be a side effect of cancer immunotherapy.

Ma hopes that his research will ultimately advance scientific understanding of acupuncture and provide practical information that can be used to improve and refine the technique. 

New research may explain the unexpected effects of common painkillers like cancer or heart disease

Do You Know The Warning Signs of Heart Disease? - YouTube

 Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and aspirin are widely used to treat pain and inflammation. But even at similar doses, different NSAIDs can have unexpected and unexplained effects on many diseases, including heart disease and cancer.

Now, a new Yale-led study has uncovered a previously unknown process by which some NSAIDs affect the body. The finding may explain why similar NSAIDs produce a range of clinical outcomes and could inform how the drugs are used in the future.

The study was published May 23 in the journal Immunity.

Until now, the anti-inflammatory effects of NSAIDs were believed to arise solely through the inhibition of certain enzymes. But this mechanism does not account for many clinical outcomes that vary across the family of drugs. For example, some NSAIDs prevent heart disease while others cause it, some NSAIDs have been linked to decreased incidence of colorectal cancer, and various NSAIDs can have a wide range of effects on asthma.

Now, using cell cultures and mice, Yale researchers have uncovered a distinct mechanism by which a subset of NSAIDs reduce inflammation. And that mechanism may help explain some of these curious effects.

The research showed that only some NSAIDs — including indomethacin, which is used to treat arthritis and gout, and ibuprofen — also activate a protein called nuclear factor erythroid 2-related factor 2, or NRF2, which, among its many actions, triggers anti-inflammatory processes in the body.

“It’s interesting and exciting that NSAIDs have a different mode of action than what was known previously,” said Anna Eisenstein, an instructor at the Yale School of Medicine and lead author of the study. “And because people use NSAIDs so frequently, it’s important we know what they’re doing in the body.”

The research team can’t say for sure that NSAIDs’ unexpected effects are due to NRF2 — that will require more research. “But I think these findings are suggestive of that,” Eisenstein said.

Eisenstein is now looking into some of the drugs’ dermatological effects — causing rashes, exacerbating hives, and worsening allergies — and whether they are mediated by NRF2.

This discovery still needs to be confirmed in humans, the researchers note. But if it is, the findings could have impacts on how inflammation is treated and how NSAIDs are used.

For instance, several clinical trials are evaluating whether NRF2-activating drugs are effective in treating inflammatory diseases like Alzheimer’s disease, asthma, and various cancers; this research could inform the potential and limitations of those drugs. Additionally, NSAIDs might be more effectively prescribed going forward, with NRF2-activating NSAIDs and non-NRF2-activating NSAIDs applied to the diseases they’re most likely to treat.

The findings may also point to entirely new applications for NSAIDs, said Eisenstein.

NRF2 controls a large number of genes involved in a wide range of processes, including metabolism, immune response, and inflammation. And the protein has been implicated in aging, longevity, and cellular stress reduction.

Said Eisenstein, “That NRF2 does so much suggests that NSAIDs might have other effects, whether beneficial or adverse, that we haven’t yet looked for.”