For the first time, researchers at the UNC School of Medicine showed they could target one brain region with a weak alternating current of electricity, enhance the naturally occurring brain rhythms of that region, and significantly decrease symptoms associated with chronic lower back pain.

The results, published in the Journal of Pain and presented at the Society for Neuroscience conference in San Diego this week, suggest that doctors could one day target parts of the brain with new noninvasive treatment strategies, such as transcranial alternating current stimulation, or tACS, which researchers used in this study to boost the naturally occurring brain waves they theorized were important for the treatment of chronic pain.

“We’ve published numerous brain stimulation papers over several years, and we always learn something important,” said senior author Flavio Frohlich, PhD, director of the Carolina Center for Neurostimulation and associate professor of psychiatry. “But this is the first time we’ve studied chronic pain, and this is the only time all three elements of a study lined up perfectly. We successfully targeted a specific brain region, we enhanced or restored that region’s activity, and we correlated that enhancement with a significant decrease in symptoms.”

Co-first author Julianna Prim, a graduate student mentored by Karen McCulloch, PT, PhD, in the Department of Allied Health Sciences at the UNC School of Medicine, who works closely with Frohlich’s lab, said, “If brain stimulation can help people with chronic pain, it would be a cheap, non-invasive therapy that could reduce the burden of opioids, which we all know can have severe side effects.”

Chronic pain is the leading cause of disability in the world, but there is not consensus among scientists that brain activity plays a causal role in the condition. Frohlich says the pain research field has focused largely on peripheral causes of chronic pain. For example, if you have chronic lower back pain, then the cause and solution lie in the lower back and related parts of the nervous system in the spine. But some researchers and clinicians believe chronic pain runs deeper, that the condition can reorganize how cells in the nervous system communicate with each other, including networks of neurons in the brain. Over time, the theory goes, these networks get stuck in a kind of neural rut, essentially becoming a cause of chronic pain.

Previous studies showed that people with chronic pain experience abnormal neural oscillations, or brain waves. There are several kinds of brain waves related to different brain regions and various kinds of brain activities – processing visual stimuli, memorization, creative thinking, etc. When we speak, think, eat, play sports, watch television, daydream, or sleep, our brain activity creates electrical patterns researchers can measure using electroencephalograms, or EEGs. These patterns fluctuate or oscillate, which is why they appear as waves that rise and fall on an EEG printout.

One type of brain activity is called alpha oscillations, which occur when we are not taking in stimuli. When we meditate in silence, daydream in the shower, or even when we’re “in the zone” during athletic activity, alpha oscillations dominate the brain. Frohlich’s lab wanted to know if these alpha oscillations were deficient in the somatosensory cortex, located in the middle portion of the brain and likely involved in chronic pain. If so, then could Frohlich’s team enhance the alpha waves there? And if that were possible, would there be any pain relief?

Prim and colleagues recruited 20 patients with lower chronic back pain. Each of them reported back pain as “four” or greater for at least six months on the subjective scale of one to 10. Each participant volunteered for two 40-minute sessions that took place one to three weeks apart.

During all sessions, researchers attached an array of electrodes to the scalps of patients. During one session, researchers targeted the somatosensory cortex using tACS to enhance the naturally occurring alpha waves. During another session for all participants, researchers used a similar weak electrical current that was not targeted – this was a sham or placebo stimulation session. During all sessions, participants felt tingling on their scalp. They could not tell the difference between the sham and tACS sessions. Also, the researchers in charge of analyzing the data did not know when each participant underwent the sham or tACS sessions, making this study double-blinded.

Co-first author Sangtae Ahn, PhD, a postdoc in Frohlich’s lab, analyzed the data, which showed that Frohlich’s team could indeed successfully target and enhance alpha oscillations in the somatosensory cortex of people with chronic lower back pain. When Prim and colleagues surveyed the participants, all of them reported a significant reduction in pain immediately following the tACS sessions, according to the subjective 0-10 pain scale. Remarkably, some participants reported feeling no pain after the tACS sessions. Participants did not report the same pain reduction after the sham stimulation sessions.

“The exciting thing is that these results occurred after just one session,” Prim said. “We hope to conduct a larger study to discover the effects of multiple tACS sessions over a longer time period.”

Frohlich said his lab also hopes to conduct studies on people with various kinds of chronic pain.

“This study is a perfect example of what’s possible when scientists and clinicians collaborate,” he said. “Ultimately, if we want to develop better treatments, cures, and prevention strategies, then these sorts of new approaches that bring researchers together are of fundamental importance.”

A modified form of botulinum toxin gives long-lasting pain relief in mice without adverse effects and, in time, could replace opioid drugs as a safe and effective way of treating chronic pain, according to research by UCL, the University of Sheffield and the Hospital for Sick Children, Toronto.

For the study, published today in Science Translational Medicine and funded by the Medical Research Council, scientists deconstructed the botulinum molecule and reassembled it with an opioid called dermorphin to make Derm-BOT – a compound which successfully targets and silences pain signals from neurons in the spinal cords of mice.

Key neurons in the spinal cord are targets for pain management as they directly ‘sense’ pain and send this information to the brain.

“Injected into the spine, Derm-BOT relieves chronic pain – such as that caused by nerve damage – and avoids the adverse events of tolerance and addiction often associated with repeated opioid drug use,” explained co-corresponding author, Professor Steve Hunt (UCL Cell & Developmental Biology).

“It doesn’t affect muscles like the botulinum toxin used to reduce wrinkles but it does block nerve pain for up to four months without affecting normal pain responses. It really could revolutionise how chronic pain is treated if we can translate it into clinic, removing the need for daily opioid intake.”

Chronic pain of ‘moderate to severe’ intensity is widespread affecting 7.8 million people in the UK and 19% of adult Europeans. It is a serious social and medical problem which negatively impacts quality of life.

Opioids like morphine and fentanyl are considered to be the gold standard for pain relief but there is little evidence that their long-term use is effective in treating chronic pain. This is because the body builds up a tolerance to repeated drug use which over the long term. Paradoxically opioids can also increase the body’s sensitivity to pain.

In the UK, 5% of the population are on opioids with 80% reporting negative side effects.

Opioid medications can also activate brain reward regions, causing addiction. Over 2 million individuals in the US have ‘opioid use disorder’ with most starting with prescribed opioid painkillers and opioid overdose is now the second leading cause of death in the US.

Previous studies in rats and companion dogs show that precise injections of tiny amounts of toxic substances, such as ‘substance P-saporin’, into the spine kill neurons responsible for crippling, chronic pain. This approach relies on an analogue of ricin which is difficult to manufacture to clinical standards and clinicians are resistant to irreversibly kill nerve cells.

In contrast, Derm-BOT is safe to manufacture, is non-toxic and does not kill neurons.

“We needed to find the best pain targeting molecular parts to direct the botulinum silencing ‘warhead’ to the pain-controlling system in the spine. For this, we developed a molecular Lego system which allows us to link the botulinum ‘warhead’ to a navigation molecule, in this case, the strong opioid called dermorphin, allowing the creation of widely desired long-lasting pain killers without the side effects of opioids,” said co-corresponding author Professor Bazbek Davletov from the Department of Biomedical Science at the University of Sheffield.

Dermorphin targets and binds to opioid receptors on the surface of neurons which allows the Derm-BOT compound to enter the cells where the botulinum ‘warhead’ then reversibly inhibits the release of neurotransmitter, silencing the cells essential for sending pain signals to the brain.

Over a five year period, 200 mice were used to simulate the early stages of human inflammatory and neuropathic pain and were treated with a single injection of either Derm-BOT, SP-BOT (a substance P-modified botulinum molecule) or morphine. The behaviour of the mice was monitored to track their pain-response and the locations and binding properties of the botulinum compounds were investigated.

“Both SP-BOT and Derm-BOT have a long-lasting effect in both inflammatory and neuropathic pain model, successfully silencing neurons without cell death. We were impressed to see that one tiny injection was enough to stop chronic pain caused by inflammation and nerve damage for at least a month.

“Furthermore, a single injection of Derm-BOT reduced mechanical hypersensitivity to the same extent as morphine. We hope to take our investigations forward with the aim of translating this into the clinic,” concluded lead author, Dr Maria Maiarù (UCL Cell & Developmental Biology).

 

Top 10 Natural Painkillers to help you get relief fast:

1. Spicy foods
2. Arnica oil
3. Turmeric and ginger
4. Peppermint and wintergreen essential oil

5. Magnesium oil or Epsom salt baths
6. Use a foam roller
7. Drink bone broth
8. Regenerative medicine (Regenexx)
9. Active release technique or deep tissue massage
10. Chiropractic care and acupuncture

 

Between a third and half (43%) of the UK population–roughly 28 million adults–lives with chronic pain, finds an analysis of the available evidence, published in the online journal BMJ Open.

This proportion is likely to rise as the population ages, warn the researchers, who add that chronic pain is a major cause of disability and distress among those affected by it.

There is no consensus on the proportion of people living with long term pain in the UK, and in a bid to try and gain an accurate picture, the researchers trawled relevant databases to find research on different types of pain, published after 1990.

Their search included studies on population based estimates of chronic pain–defined as lasting more than 3 months–chronic widespread pain, fibromyalgia (a rheumatic condition characterised by muscular or musculoskeletal pain), and chronic neuropathic pain (pain caused by nerve signalling problems).

From among 1737 relevant articles, 19 studies, involving just under 140,000 adults, were deemed suitable for inclusion in the final analysis.

They pooled the study data to arrive at an estimate of the prevalence of chronic pain, overall, and chronic widespread pain. Summary estimates were also drawn up for moderate to severely disabling chronic pain, fibromyalgia, and chronic neuropathic pain among UK adults.

Based on seven studies, the researchers worked out that the prevalence of chronic pain ranged from 35% to 51% of the adult population, with the prevalence of moderate to severely disabling chronic pain (based on four studies), ranging from 10% to 14%–equivalent to around 8 million people.

Pooling of the data showed that 43% of the population experience chronic pain, and 14% of UK adults live with chronic widespread pain. The summarised data also showed that 8% of UK adults experience chronic neuropathic pain, and 5.5% live with fibromyalgia.

Twelve of the studies categorised the prevalence of pain by age group, and unsurprisingly, these showed that older people were more likely to live with pain over the long term.

Among 18-25 year olds, the prevalence was 14%, although it may be as high as 30% among 18-39 year olds, the analysis indicates–a sizeable chunk of the working population, say the researchers.

Among those aged 75 and above, the prevalence was almost two thirds (62%), suggesting that if current trends continue, the burden of chronic pain may increase further still as the population ages, say the researchers.

Women were more likely than men to be affected by chronic pain, irrespective of age or pain type.

The researchers point out that the included studies varied considerably, and that not all of them were of high quality, so making it difficult to draw firm conclusions.

The studies showed gradually increasing prevalence of chronic pain over time, from 1990. And the researchers estimate that the prevalence of chronic pain in the UK is now around 43%, equating to around 28 million people, based on population stats for 2013.

“Such prevalence data does not itself define need for care or targets for prevention, but reliable information on prevalence will help to drive public health and healthcare policymakers’ prioritisation of this important cause of distress and disability in the general population,” they conclude.