An independent panel convened by the National Institutes of Health concluded that individualized, patient-centred care is needed to treat and monitor the estimated 100 million Americans living with chronic pain. To achieve this aim, the panel recommends more research and development around the evidence-based, multidisciplinary approaches needed to balance patient perspectives, desired outcomes, and safety.

“Persons living with chronic pain have often been grouped into a single category, and treatment approaches have been generalized with little evidence to support this practice,” said Dr. David B. Reuben, panel chair and professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles. “Chronic pain spans a multitude of conditions, presents in different ways, and requires an individualized, multifaceted approach.”

Chronic pain is often treated with prescription opioids, but the panel noted widespread concern with this practice. Although some patients benefit from such treatment, there are no long-term studies on the effectiveness of opioids related to pain, function, or quality of life. There is not enough research on the long-term safety of opioid use. However, there are well-documented potential adverse outcomes, including substantial side effects (e.g., nausea, mental clouding, respiratory depression), physical dependence, and overdose — with approximately 17,000 opioid-related overdose deaths reported in 2011.

“Clearly, there are patients for whom opioids are the best treatment for their chronic pain. However, for others, there are likely to be more effective approaches,” stated Dr. Reuben. “The challenge is to identify the conditions for which opioid use is most appropriate, the alternatives for those who are unlikely to benefit from opioids, and the best approach to ensuring that every patient’s individual needs are met by a patient-centered health care system.”

The panel identified several barriers to implementing evidence-based, patient-centered care. For example, many clinicians do not have tools to assess patient measures of pain, quality of life, and adverse outcomes. Primary care practices often do not have access to multidisciplinary experts, such as pain management specialists. Insurance plans may not cover team-based, integrative approaches that promote comprehensive, holistic care. In addition, some plans do not offer effective non-opioid drugs as first-line treatment for chronic pain, thus limiting a clinician’s ability to explore other avenues of treatment. Once a health provider has made the decision to use opioids, there are insufficient data on drug characteristics, dosing strategies, or tapering to effectively guide clinical care.

“We have inadequate knowledge about treating various types of pain and how to balance effectiveness with potential harms. We also have a dysfunctional health care delivery system that promotes the easiest rather than the best approach to addressing pain,” noted Dr. Reuben.

To address knowledge gaps, the panel cited a need for more research on pain, multidisciplinary pain interventions, the long-term effectiveness and safety of opioids, as well as optimal opioid management and risk mitigation strategies. However, because well-designed longitudinal studies can be large, expensive, and difficult for recruitment, the panel encouraged the development of new research design and analytic methods to answer important research and clinical questions.

The panel also recommended engaging electronic health record vendors and health systems to provide pain management decision support tools for clinicians. In addition, the panel advised the NIH and other federal agencies to sponsor more conferences to harmonize pain assessment and treatment guidelines to facilitate consistent clinical care for the treatment of chronic pain.

A protein found in tick saliva could be turned into a drug that eases itching and chronic pain in people.

New research has shown that the protein – called Votucalis – provided pain and itch relief in research involving mice.

The findings from Durham and Newcastle Universities, in collaboration with pharmaceutical company Akari Therapeutics Plc, could lead to a replacement for traditional painkillers, for example opioids, that can be ineffective, can have serious side-effects and can be addictive.

The research is published in the journal Frontiers in Pharmacology.

Votucalis is derived from the saliva of ticks – in this case the brown-ear tick Rhipicephalus appendiculatus – who secrete the protein into their host when feeding so the host is unaware that they have been bitten.

Votucalis is a biologic drug that works by binding histamine, produced in the body, with high-affinity and thereby prevents histamine activating its four cell surface receptors resulting in reduced itch or chronic pain responses.

Conditions that cause chronic pain or itching include atopic dermatitis, psoriasis, arthritis, diabetes, sciatica, back injuries.

Study co-author Dr Paul Chazot, in the Department of Biosciences, Durham University, UK, said: “Persistent or chronic pain is a huge global health challenge, which affects over 20 per cent of the population.

“It is the single biggest reason that people in the UK visit their doctor and it is recognised as a priority disease by the World Health Organisation.

“The National Institute for Health and Care Excellence (NICE) has recommended that current opioid and gabapentinoid pain medications should not be prescribed to patients newly diagnosed with chronic pain (*Footnote 1), apart from cancer sufferers, so there is an urgent need to develop a new, long-lasting medication that is both effective and safe to use.

“Our study is the first to show evidence of the anti-itch and pain relief potential of Votucalis, which is very exciting. We could be on the brink of discovering a viable alternative to opioid and gabapentinoid drugs.”

Unlike opioids – which are morphine-based – the research shows that Votucalis does not enter the brain, which means it is not addictive and less likely to cause side-effects. It can be manufactured in large amounts using recombinant methods.

Study co-author Dr Ilona Obara, began the research with Dr Chazot while at Durham and continued the work after moving to the School of Pharmacy, Newcastle University, UK.

Dr Obara said: “It is amazing that a protein found in the saliva of this tiny creature could prevent chronic pain and itching in people.

“These are conditions that bring a huge amount of misery, and current medication displays limited efficacy, and can also often be detrimental to patients.

“Votucalis has already been tested in humans with other conditions, including conjunctivitis, without major side-effects, so the potential for this to be developed into a drug to tackle chronic pain and itching is definitely there.”

The researchers say the next step towards clinical testing is to develop a delivery system to effectively administer the drug at the site of itch and pain.

Votucalis is a pipeline drug for Akari Therapeutics Plc (UK), and Drs Chazot and Obara are co-authors on its patent for neuropathic and inflammatory pain.

Mr Clive Richardson, Chief Executive Officer of Akari Therapeutics Plc (UK), said: “We are delighted to be working with Drs Chazot and Obara on the pipeline drug Votucalis. The exciting new data in pain and itch supports the potential that the unique mode of action of Votucalis, inhibiting all four histamine receptors, opens exciting therapeutic opportunities in pain management and dermatology.”

The research has been funded by a PhD scholarship from the Saudi Arabian government, and partially funded by Akari Therapeutics Plc and the Medical Research Council Confidence in Concept scheme.

Biochemist Laura Bohn, PhD, and Sr. Staff Scientist Edward Stahl describe a compound called SR-17018, which activates the same pain-relieving receptor as opioid drugs, however it binds in a different way, augmenting pain relief while diminishing overdose risk in mouse studies. CREDIT Courtesy of Scripps Research

 Scientists at Scripps Research in Florida have created a collection of new pain-relieving compounds that, like morphine and other drugs, provide relief via activation of opioid receptors, but without inducing many dangerous and unwanted side-effects that have driven opioid-related overdose and deaths.

Writing Nov. 22 in the journal the Proceedings of the National Academies of Sciences, biochemist Laura Bohn, PhD, and colleagues describe a compound called SR-17018, which activates the same pain-relieving receptor as opioid drugs including morphine, oxycodone and fentanyl; however it binds to opioid receptors in a different way from those drugs, leaving the opioid receptor open and available to the body’s own natural pain-relieving substances, apparently augmenting pain relief. In a study published earlier this year (Pantouli et al., 2021, Neuropharmacolgy), the group showed that the compound performed particularly well in mouse studies of chemotherapy-induced neuropathic pain, the scientists write.

In the current report, the authors have made strides in understanding why these drugs seem so different. 

“We demonstrate that these compounds bind to a different site on the receptor than a typical opioid. Because of that, they seem to leave the receptor on and yet still receptive to endogenous opioids,” says Bohn, who chairs the Scripps Research Department of Molecular Medicine in Jupiter, Florida. “In neuropathy pain, we show they are far superior to morphine and oxycodone; moreover, SR-17018 does not decrease breathing.”

The authors also described a related compound that, being more potent, induces respiratory suppression, but at higher doses than are needed to relieve pain.  Importantly for safety, this compound, SR-14968, proved responsive to overdose rescue medication naloxone, when given at doses high enough to suppress breathing.

Perhaps most importantly for people with severe chronic pain, SR-17018 showed an ability to provide sustained pain relief over time without development of tolerance, the problem of reduced efficacy over time that requires increased doses, increasing danger of overdose.

The paper’s first author, Edward L. Stahl, notes that the new compounds are referred to as “biased agonists,” because they activate the mu opioid receptor in a way that preferentially engages one of its signaling pathways, the one that provides pain relief, over other pathways such as those that lead to suppressed breathing.

“The compound SR-17018 is the first biased agonist of the mu opioid receptor that does not lead to tolerance with chronic use,” says Stahl, a senior staff scientist in the Bohn lab. “This is a desirable feature for potential use in the context of chronic, severe pain.”

The new compounds were engineered to avoid the “beta-arrestin” signaling cascade that leads to opioids’ dangerous and unwanted traits, including respiratory suppression, a cause of overdose, and constipation, he adds.

Opioid medications remain a go-to treatment for severe pain, whether it’s from surgery, a sudden injury, or nerve damage. But as opioid addiction and overdose deaths reach new highs in the United States, the need for safer ways to treat acute pain has grown more urgent, Bohn says.  

In work spanning more than two decades, Bohn and her team have demonstrated the feasibility of untangling the pain-relieving properties of opioids from their negative traits. Her work has not only broadened understanding of how opioid receptors work to direct multiple physiological responses, it has pointed the field toward potentially safer options for providing relief from severe pain.

Bohn’s research group has engineered multiple compounds which, in mouse studies, diminish activation of beta-arrestin signaling. Additional problems of opioids continue to pose challenges, including dependance, or addiction. The fact that SR-17018 avoids tolerance with chronic use is good news, Bohn says. Also good news is how it wears off, she adds.

“The compound showed a nice, slow tapering. That, in itself, may help curb some of the dependence problems. A drug like morphine provides a quick rush then a quick clear, and you need the rush again.”

Going forward, the team is continuing to refine and test the compounds so that they could eventually be tested in a clinical setting.

“Severe and chronic pain associated with surgery, nerve damage, and trauma require strong pain relief,” Bohn says. “Safer solutions are needed. We believe these new compounds are a big step in the right direction.”

Bull ant in best credit Sam Robinson, University of Queensland

Australian bull ants have evolved a venom molecule perfectly tuned to target one of their predators – the echidna – that also could have implications for people with long-term pain, University of Queensland researchers say.

Dr Sam Robinson and David Eagles from UQ’s Institute for Molecular Bioscience found a bull ant venom component that exploits a pain pathway in mammals, which they believe evolved to stop echidnas attacking the ant’s nests.

“Venoms are complex cocktails and while bull ant venom contains molecules similar to those found in honey bee stings which cause immediate pain, we also found an intriguing new molecule that was different,” Dr Robinson said.

Whilst searching databases for similar amino-acid sequences, Dr Robinson found that the molecule matched the sequence of mammalian hormones related to Epidermal Growth Factor (EGF), and of these, was most closely related to that of the echidna.

“We tested the venom molecule on mammalian EGF receptors and it was very potent – this convinced us that the venom molecule was there to defend against mammals,” he said.

“We went on to show that while it didn’t cause direct pain, the molecule did cause long-lasting hypersensitivity.

“Many small carnivorous marsupials, like bandicoots, eat individual ants, but only the echidna is known to attack bull ant nests and target their young – we think that making the echidna sensitive to pain, in tandem with the immediate ‘bee-sting’ pain, may dissuade it from returning to the nests.

“You can see clearly in the ant’s DNA that it is producing a molecule that mimics a hormone of its natural enemy and is using it as a weapon against it – it brings to mind the ancient proverb ‘to know your enemy, you must become your enemy.’”

The team believes the links between EGF signalling and chronic pain are building momentum and is confident this study could inspire new ways to treat long-term pain.

EGF-inhibitor drugs are readily available on the market and used in anti-cancer therapy to slow tumour growth, with evidence suggesting patients that take them experience less long-term pain.

“We hope that by highlighting the role of this signalling pathway in pain, we can encourage different strategies for pain treatment, especially long-term pain for which treatment is currently limited,” Dr Robinson said.

The intention of The Analgesic Museum is to seed an international interdisciplinary network of scientists, museum and healthcare professionals, individuals living with persistent pain and artists committed to exploring the aesthetics and impact of museum engagement to reduce the burden of persistent pain. UC REGENTS

Philosophers have argued for centuries that the arts can draw the individual from isolation, create purpose and enliven existence. But can the arts also relieve pain? 

On March 11, Ian Koebner, an assistant professor in the Division of Pain Medicine at the UC Davis School of Medicine, is co-hosting a free, half-day virtual conference on the topic in Amsterdam. Called “The Analgesic Museum,” the event starts at 9:30 CET (12:30 a.m. PST) and will explore the different ways the arts can reduce the burden of pain.

Anyone who registers for the event can later view the conference recording (for those in the U.S. who are not night owls). 

“The public health potential of cultural engagement is an exciting field of study,” said Koebner, who is also the director of Integrative Pain Management at UC Davis Health. “The Analgesic Museum conference is bringing together an internationally renowned group of artists, scholars, and practitioners from diverse fields to explore the intersection of art and pain management practices. The opportunity for new research, exhibitions and artistic works is tremendous.”

The Institute of Advanced Studies, University of Amsterdam, CLUE+ and PULSE Network – Vrije University Amsterdam, University College London and Tilburg University are co-hosting the event. 

Featured speakers include:

• Christopher Bailey, arts and health lead for the World Health Organization
• Melissa Menzer, senior program analyst for the National Endowment for the Arts, and
• Jasminko Halilovic, founder and managing director of the War Childhood Museum in Sarajevo, Bosnia and Herzegovina. 

Topics discussed by the international group of artists, health professionals, museum curators, and scholars will include: 

• Arts strategies for addressing the opioid crisis
• Research and creative scholarship to explore how museum-based interventions can lessen pain
• Exhibition development to showcase the aesthetics of analgesia
• Arts experiences and practices to reduce the burden of pain 

In both the United States and Europe, an estimated 20% of adults experience chronic pain. Chronic pain is pain that lasts for three or more months. It is often resistant to medical treatment. 

The intention of The Analgesic Museum conference is to seed an international interdisciplinary network. It will include scientists, museum and healthcare professionals, individuals living with chronic pain and artists committed to exploring the aesthetics and impact of museum engagement to reduce the burden of chronic pain. 

Koebner created the successful and popular collaboration with Crocker Art Museum in Sacramento, Art RX. The program used specialized in-person museum tours (now presented virtually via Zoom) and discussions as a way to decrease pain and social disconnection for people with chronic pain. Koebner’s research showed participants experienced Art Rx as a positive and inclusive experience, with potential lasting benefit. 

Link here for more information and to register: https://ucdavishealth.zoom.us/webinar/register/WN_nxhVaSB-Rn6YUTyi5iVo0Q