Pain Management

Posted on Pain Management

Chronic pain linked to socioeconomic background – new study

Development of chronic musculoskeletal pain can be influenced by socioeconomics, fear of movement, smoking and poorer support networks, new research shows. 

In a systematic review of current evidence, researchers found that people from a lower socioeconomic background were twice as likely to develop chronic pain following injury.  

Those with a combination of characteristics, including smoking, high level of pain at the time of injury, fear of movement, poorer support networks and a lower level of education or household income, maybe seven times more likely to develop chronic pain after an injury. The results are published in PLOS One. 

Pain is described as ‘acute’ when it has been present for a short period of time – anything that lasts for less than three months after initial injury. Pain is described as chronic when it has been present for longer than three months after initial injury. Chronic musculoskeletal pain affects about 43 per cent of the UK population and is the greatest cause of disability worldwide, often persisting for many years or indefinitely. People with chronic pain often experience poorer quality of life and are also more likely to develop diseases including cancer, cardiovascular diseases and diabetes.  

Current approaches to managing chronic pain focus on physical rehabilitation at the site of the pain, or injury. However, the body’s healing process usually takes place over no longer than three months, suggesting that the reasons for longer-term pain are more complex. 

Lead author Michael Dunn, of the University of Birmingham and St. George’s University Hospitals NHS Foundation Trust, said: “The purpose of acute pain is to alter behaviour to protect the body from harm, but chronic pain persists because of a sensitised nervous system that continues our experience of pain, even after the healing process has completed.”  

This process, the researchers found, is influenced by a range of psychological and social factors and so treatment which focuses solely on the injured body part is often ineffective. 

Mr Dunn continued: “The characteristics that we have identified are related particularly to an individual’s experiences, rather than a type of injury. For that reason, approaches to treating people with musculoskeletal injuries should be more person-centred, focusing on broader biological, psychosocial and social well-being. Put simply, current healthcare approaches do not address all the reasons people do not get better.” 

The researchers also identified other factors related to developing chronic pain, such as lower job satisfaction, stress and depression. These characteristics were supported by lower quality evidence, but are also linked to lower socioeconomic backgrounds. 

“People from lower socioeconomic backgrounds are twice as likely to develop chronic pain after injury. This indicates that not only are current healthcare approaches inadequate, they may also be discriminatory, with current healthcare approaches that are orientated around the injured body part being geared towards those from higher socioeconomic backgrounds who are less likely to experience these psychological or social factors,” said Mr Dunn.  

Posted on Pain Management, Rheumatoid arthritis

Why some people with rheumatoid arthritis have pain without inflammation

Synovial tissue

In this image, abnormal synovial tissue is shot through with excessive tissue growth, including blood vessels (in magenta). Synovium should be thin and smooth. CREDIT Bai et al.

Treatment for rheumatoid arthritis (RA) has come a long way in recent years. In many cases, a battery of medications can now successfully stymy the inflammatory cells that cause swelling and pain when they infiltrate tissues around the joints.

Yet for some reason, about 20% of patients with painful, visibly swollen joints consistently get no relief from multiple rounds of even the strongest of these anti-inflammatory drugs.

Surgical interventions intended to remove inflamed tissue have revealed why: “In some cases, their joints aren’t actually inflamed,” says co-senior author Dana Orange, an associate professor of clinical investigation in Rockefeller’s Laboratory of Molecular Neuro-oncology. “With these patients, if you press on the joint, it feels mushy and thick to the touch, but it’s not caused by the infiltrating immune cells. They have excessive tissue growth, but without inflammation. So why are they experiencing pain?”

She and her colleagues suggest an explanation in a new paper in Science Translational Medicine. These patients have a suite of 815 genes that activate abnormal growth of sensory neurons in tissues that cushion the affected joints.

“These 815 genes are rewiring the sensory nerves, which explains why anti-inflammatory drugs don’t work to alleviate pain for these patients,” says Orange. The findings may lead to new treatments for these outliers.

A puzzling disconnection

Rheumatoid arthritis is a tricky chronic disease. Its symptoms—stiffness, tenderness, swelling, limited motion, and pain—slowly emerge in the hands, wrists, feet, and other joints. It occurs symmetrically (not just in one hand but in both, for instance) and sporadically, with irregular flare-ups. Extreme fatigue and depression are also common.

Most cases of RA are caused by products of immune cells such as cytokines, bradykinins, or prostanoids invading the synovium—a soft tissue lining the joints—where they bind to damage-sensing pain receptors. Drugs that target immune mediators have made RA a far more tolerable condition for most, but those suffering from the disconnection between inflammation and ache haven’t benefitted.

Doctors often prescribe these patients drug after anti-inflammatory drug in an ultimately fruitless attempt to give relief. As a result, “we are subjecting some patients to a lot of medications that cause immunosuppression and yet have little chance of making their symptoms better,” Orange says.

She and her colleagues sought answers in the genes expressed in the joint tissue samples of these patients.

Genetic culprits

The researchers looked at tissue samples and self-reported pain reports from 39 patients with RA who had pain but little inflammation. They also developed a machine-learning analysis that they coined graph-based gene expression module identification (GbGMI).

GbGMI tests every possible combination of genes in a dataset to determine the optimal set of genes that together associate with a targeted clinical feature—in this case, pain.

Using RNA sequencing, the researchers found that of the 15,000 genes expressed in the tissue samples, about 2,200 had increased expression in the 39 patients. Using GbGMI, they identified 815 genes that together associated with patient reports of pain.

“This is a challenging problem, because we have a large number of genes but a limited number of patients,” says co-senior author Fei Wang, professor of population health sciences and founding director of the Institute of Artificial Intelligence for Digital Health at Weill Cornell Medicine. “The graph-based approach we used effectively explored the collective associations between a gene set and patient-reported pain.”

Single cell sequencing analysis found that of the four types of fibroblasts in synovial tissue, CD55+ fibroblasts exhibited the highest expression of pain-associated genes. Located in the outer synovial lining, CD55+ cells secrete synovial fluid, allowing for frictionless joint movement. They also expressed the NTN4 gene, which codes for a protein called Netrin-4. Proteins in the netrin family guide axon growth paths and promote new vascular growth.

Surprising pain pathways

These genes, it turned out, were enriched in pathways that are important for neuron axon growth, the researchers discovered. The keys to sensation, sensory neurons receive and transmit information to the central nervous system. Axons are the tendrils that branch out from them into tissues.

“That led us to hypothesize that perhaps the fibroblasts are producing things that alter the growth of sensory nerves,” Orange says.

But what role was the protein playing in the sensation of pain?

To find out, they grew neurons in vitro and then doused them with Netrin-4, which sparked the sprouting and branching of CGRP+ (gene-related peptide) pain receptors. It’s the first time that Netrin-4 has been shown to alter the growth of pain-sensitive neurons, she notes.

Imaging of RA synovial tissue also revealed an overabundance of blood vessels, which feed and nurture new cells. These vessels were encased by CGRP+ sensory nerve fibers and were growing towards the lining fibroblasts in areas of excessive tissue growth, or hyperplasia. This process likely leads to the squishy swelling that many rheumatologists and surgeons have mistaken for inflammation.

Better drugs

In the future, the researchers aim to home in on other products that fibroblasts may be producing that can affect the growth of pain-sensitive neurons. They’ll also delve into the other types of sensory nerves that might be affected.

“We studied one type, but there are about a dozen. We don’t know if all nerves are affected equally. And we don’t want to block all sensation. Sensory nerves are important for knowing that you should avoid certain movements and the position of your joint in space, for instance,” Orange says.

“We want to drill down on those details so that hopefully we can come up with other treatments for patients who don’t have a lot of inflammation. Right now, they’re taking medications that can cost $70,000 a year but have no chance of working. We must do a better job of getting the right drug to the right patient.”

Posted on Fibromyalgia, Pain Management

How to tell if your pain is from Fibro – and how to talk to you doctor about it.

Are you or a loved one living with unexplained pain? In this enlightening episode, Dr. Elizabeth Ortiz breaks down the science behind Nociplastic pain and offers valuable insights to start the Fibro conversation with your doctor! Video Key Takeaways Fibromyalgia is a clinical syndrome characterized by widespread musculoskeletal pain, along with associated symptoms like fatigue, sleep disturbances, mood disorders, and brain fog. Fibromyalgia is a real condition with genuine pain.

The pain of fibromyalgia is termed “Nociplastic pain,” which results from a dysregulated nervous system, leading to hypersensitivity to pain signals. Fibromyalgia pain can manifest as deep, aching pain that is not logically connected to a specific injury, and it can occur on both sides of the body and above and below the waist. It’s essential to discuss the possibility of fibromyalgia with a doctor, explore medication options, and consider lifestyle changes such as diet, sleep, movement, and community support to manage fibromyalgia pain effectively.

Posted on Pain Management

CBD products don’t ease pain and are potentially harmful – new study finds

There is no evidence that CBD products reduce chronic pain, and taking them is a waste of money and potentially harmful to health, new research finds
There is no evidence that CBD products reduce chronic pain, and taking them is a waste of money and potentially harmful to health, new research finds

There is no evidence that CBD products reduce chronic pain, and taking them is a waste of money and potentially harmful to health, according to new research led by the University of Bath in the UK.

CBD (short for cannabidiol) is one of many chemicals found naturally in the cannabis plant. It’s a popular alternative medicine to treat pain and is readily available in shops and online in the form of oils, tinctures, vapes, topical creams, edibles (such as gummy bears) and soft drinks.

However, consumers would do well to steer clear of these products, according to the new study.

“CBD presents consumers with a big problem,” said Professor Chris Eccleston, who led the research from the Centre for Pain Research at Bath. “It’s touted as a cure for all pain but there’s a complete lack of quality evidence that it has any positive effects.”

He added: “It’s almost as if chronic pain patients don’t matter, and that we’re happy for people to trade on hope and despair.”

For their study, published this week in The Journal of Pain, the team – which included researchers from the Universities of Bath, Oxford and Alberta in Canada – examined research relevant to using CBD to treat pain and published in scientific journals up to late 2023.

They found:

  • CBD products sold direct to consumers contain varying amounts of CBD, from none to much more than advertised.
  • CBD products sold direct to consumers may contain chemicals other than CBD, some of which may be harmful and some illegal in some jurisdictions. Such chemicals include THC (tetrahydrocannabinol), the main psychoactive component of the cannabis plant.
  • Of the 16 randomised controlled trials that have explored the link between pain and pharmaceutical-grade CBD, 15 have shown no positive results, with CBD being no better than placebo at relieving pain.
  • A meta-analysis (which combines data from multiple studies and plays a fundamental role in evidence-based healthcare) links CBD to increased rates of serious adverse events, including liver toxicity.

Medical vs non-medical CBD

In the UK, medical cannabis is the only CBD product that is subject to regulatory approval. It’s occasionally prescribed for people with severe forms of epilepsy, adults with chemotherapy-related nausea and people with multiple sclerosis.

Non-medical CBD is freely available in the UK (as well as in the US and many European countries) so long as it contains negligible quantities of THC or none at all. However, CBD products sold on the retail market are not covered by trade standards, meaning there is no requirement for them to be consistent in content or quality.

Most CBD products bought online – including popular CBD oils – are known to contain very small amounts of CBD. Moreover, any given product may be illegal to possess or supply, as there’s a good chance it will contain forbidden quantities of THC.

Chronic pain

An estimated 20% of the adult population lives with chronic pain, and sufferers are often desperate for help to alleviate their symptoms. It’s no surprise then that many people reach for CBD products, despite their high price tag and the lack of evidence of their effectiveness or safety.

Dr Andrew Moore, study co-author and former senior pain researcher in the Nuffield Division of Anaesthetics at the University of Oxford, said: “For too many people with chronic pain, there’s no medicine that manages their pain. Chronic pain can be awful, so people are very motivated to find pain relief by any means. This makes them vulnerable to the wild promises made about CBD.”

He added that healthcare regulators appear reluctant to act against the spurious claims made by some manufacturers of CBD products, possibly because they don’t want to interfere in a booming market (the global CBD product market was estimated at US$3 billion in 2021 or £2.4 billion and is anticipated to reach US$60 billion by 2030 or £48 billion) especially when the product on sale is widely regarded as harmless.

“What this means is that there are no consumer protections,” said Dr Moore. “And without a countervailing body to keep the CBD sellers in check, it’s unlikely that the false promises being made about the analgesic effects of CBD will slow down in the years ahead.”

The study’s authors are calling for chronic pain to be taken more seriously, with consumer protection becoming a priority.

“Untreated chronic pain is known to seriously damage quality of life, and many people live with pain every day and for the rest of their lives,” said Professor Eccleston. “Pain deserves investment in serious science to find serious solutions.”

Posted on Pain Management

Did you know that physical activity can protect you from chronic pain? One of the reasons is that it increases your pain tolerance

Kayakers in northern Norway

UiT researchers have found that physically active people have a lower risk of experiencing chronic pain several years later. “This suggests that physical activity increases our ability to tolerate pain and may be one of how activity helps to reduce the risk of developing severe chronic pain,” says doctoral fellow Anders Årnes. David Jensen/UiT The Arctic University of Norway

In 2023, researchers from UiT The Arctic University of Norway, the University Hospital of North Norway (UNN), and the Norwegian Institute of Public Health found that among more than 10,000 adults, those who were physically active had a higher pain tolerance than those who were sedentary; and the higher the activity level, the higher the pain tolerance.

After this finding, the researchers wanted to understand how physical activity could affect the chances of experiencing chronic pain several years later. And they wondered if this was related to how physical activity affects our ability to tolerate pain.

“We found that people who were more active in their free time had a lower chance of having various types of chronic pain 7-8 years later. For example, being just a little more active, such as going from light to moderate activity, was associated with a 5% lower risk of reporting some form of chronic pain later,” says doctoral fellow Anders Årnes at UiT and UNN.

He is one of the researchers behind the study.

He adds that for severe chronic pain in several places in the body, higher activity was associated with a 16% reduced risk.

Measured cold pain tolerance

The researchers found that the ability to tolerate pain played a role in this apparent protective effect. That explains why being active could lower the risk of having severe chronic pain, whether or not it was widespread throughout the body.

“This suggests that physical activity increases our ability to tolerate pain and may be one of the ways in which activity helps to reduce the risk of severe chronic pain,” says Årnes.

The researchers included almost 7,000 people in their study, recruited from the large Tromsø survey, which has collected data on people’s health and lifestyle over decades.

After obtaining information about the participants’ exercise habits during their free time, the researchers examined how well the same people handled cold pain in a laboratory. Later, they checked whether the participants experienced pain that lasted for 3 months or more, including pain that was located in several parts of the body or pain that was experienced as more severe.

Among the participants, 60% reported some form of chronic pain, but only 5% had severe pain in multiple parts of the body. Few people experienced more serious pain conditions.

The research was recently published in the journal PAIN – Journal of the International Association for the Study of Pain.

Pain and exercise

When it comes to exercising if you already have chronic pain, the researcher says:

“Physical activity is not dangerous in the first place, but people with chronic pain can benefit greatly from having an exercise program adapted to help them balance their effort so that it is not too much or too little. Healthcare professionals experienced in treating chronic pain conditions can often help with this. A rule of thumb is that there should be no worsening that persists over an extended period of time, but that certain reactions in the time after training can be expected.”