By Frank Kumli, Head of Innovation and Entrepreneurship at Basel Area Business & Innovation, and Cécile Tardy-Srinivasan, Manager of DayOne Accelerator

Pain is a crucial sensation for survival, but it can also drive us to depression and long-term suffering if not managed correctly. Alarmingly, chronic pain affects more than 30 percent of people worldwide, [1] yet current treatments can be ineffective or lead to drug dependence, leaving many individuals in dire need of innovative solutions that will help them find relief. In response, researchers are exploring ground-breaking ways to manage pain – from neuroplasticity training through interactive games to therapies that use virtual reality (VR) – which promise to shake up the status quo of clinical pain management in the years to come. In fact, these fascinating approaches are already finding their place in forward-thinking healthcare institutions, supported by the healthtech sector, which is booming in multiple locations around Europe, especially in the Basel area in Switzerland.

Pain is a complex and multifaceted biomechanism that is experienced differently by each person. Its subjective nature means that it can’t be measured or quantified; a person’s perception of pain is unique and influenced by various factors, including genetics, past experiences, and emotional state. Psychosocial elements – such as mood, stress levels, and  support systems – also shape how a person perceives and copes with pain. This complex web of factors has plagued healthcare professionals for a long time, making chronic pain treatment incredibly challenging. Traditional therapies offer temporary relief, but long-term use can lead to dependence and addiction, which is evident with the opioid crisis in countries such as the  US. Many clinicians are therefore looking for alternative treatments, while also seeing the benefits of taking a more holistic approach to the pain management paradigm.

Dr Elan Schneider is CEO and Co-founder of the Israeli company TrainPain – comprised of a team of healthcare professionals, scientists, and technology experts who have developed a neuroplasticity training game for chronic pain. Dr Schneider has dedicated the best part of his career to finding novel solutions for treating pain. He explained: “Pain can destroy a person’s quality of life for prolonged periods, yet there isn’t always a clear correlation between the physical damage in the body and the intensity of pain felt. The latest understanding of pain suggests that neuroplastic changes can heighten the sensitivity of the body’s pain-processing nerves. This means that even minor threats to the body can trigger pain, amplifying these nerve signals and resulting in disproportionate levels of pain relative to the actual harm.

“Despite extensive research in this field, many findings haven’t made their way into clinical practice. At TrainPain, we’ve translated some ground-breaking concepts from neuroscience into tangible solutions. Our method is to train the body’s natural ability to regulate pain by enhancing the neural circuits that naturally turn down the volume of pain-related nerve signals sent to the brain. While this approach isn’t new – opioids and cannabinoids, for example, work similarly to mimic the body’s inhibitory neurotransmitters – traditional medications not only come with side effects, but also fail to promote the body’s inherent learning capabilities for long-term changes in pain regulation.”

Transdiagnostic pain management

The team at TrainPain has taken a transdiagnostic approach to pain management, looking at mechanisms that are common across different types of chronic pain. This could help to meet the dire need for novel therapies for neuropathic pain – including fibromyalgia, complex regional pain syndrome, and phantom limb pain – where current treatments are largely ineffective or insufficient.

Dr Schneider continued: “Various conditions display an overlap, with neuroplasticity in the nervous system being a pivotal factor. Engaging in numerous repetitions of therapeutic tasks can help address these maladaptive neuroplastic changes and promote healthier alterations in the nervous system. To this end, our solution harnesses sensory perception tasks, delivered through video games, to provide the necessary engagement and ensure that patients participate for sufficient time to benefit. This form of training aids learning and induces changes in how sensory neurons activate and communicate.”

Basel: a hub for scaling innovation

TrainPain is one of a handful of companies attracted to Basel, Switzerland, which is now arguably the healthtech capital of Europe. Basel and the surrounding area are replete with highly specialized scientific entrepreneurs and large pharmaceutical players, where growing companies such as TrainPain can be immersed in a forward-thinking environment to foster innovation. The company signed up for the DayOne Accelerator with Basel Area Business & Innovation – a non-profit agency that helps innovative companies develop and expand – to make the vital connections it needed to take its ideas to the next level and, ultimately, reach the patients they are designed to help.

Commenting on the accelerator, Dr Schneider said: “Participating in this accelerator gave us the opportunity to talk with the right people at the intersection of pharma and digital health. We learned a lot about the pharmaceutical industry and its needs, where our solution fits, and how to make important collaborations with healthcare organizations to ensure we are ready for the future.”

Another alum of the DayOne Accelerator is Rescape, a Welsh startup that develops VR solutions for reducing pain and anxiety. Rescape knew about the beneficial ecosystem of the Basel area, which helped the company take its innovation from conception to completion. Matt Wordley, Co-founder and Board Director at Rescape, explained: “We don’t get much exposure to pharmaceutical companies in Wales, so spending time in Basel has been crucial for our development as a small startup. It has allowed us to understand the complexities of the pharma world, and network with the right people. In fact, a couple of the collaborations born out of our time in Basel have really helped us fast-track our business, and a number of other opportunities are still being pursued. The team at Basel Area Business & Innovation has also opened the doors to mainland Europe, helping our
VR solutions conform to the EU medical device regulations.”

Virtual reality in healthcare

VR is most often associated with gaming, but its applications are being explored in a variety of industries. In healthcare, a recent analysis of VR and augmented reality in scientific literature found more than 8,000 research papers on the topic, with the most common medical conditions under investigation including pain, stroke, anxiety, depression, fear, cancer, and neurodegenerative disorders. [2] Pain and anxiety management have the largest evidence base for the use of VR in medicine, [3] where distraction through immersion – along with neurophysiological changes – contribute to therapeutic effects. This could lead to novel treatment options for patients with chronic pain, potentially reducing the reliance on opioids. [4] In addition, Rescape is already seeing significant benefits in a more acute setting.

Wordley explained: “The brain becomes ensconced in the environment that it is in, as it is not designed to cope with two realities. With VR, we are basically hacking the brain, so it shelves the pain or anxiety the patient is experiencing, and replaces it with a distracting or relaxing environment. We have found some wonderful results in paediatric patients, especially with children who are stressed or anxious about minor procedures, such as those involving needles. VR can actually help to reduce sedation requirements in children, and potentially eliminate the need for anaesthesia for minor operations. This is a huge benefit to both anxious children and stressed parents, as well as healthcare professionals, reducing the risks and recovery times for patients.”

Wordley continued: “VR is also being deployed in palliative care as a temporary respite for patients – a form of escapism – and in intensive care units (ICUs). A nice example in the latter setting involved a patient who was having around 20 panic attacks per day following an extended ICU stay, where he experienced pain and isolation from the outside world. Within a couple of weeks of using VR, he was having just the odd panic attack, and could be moved to a general ward. However, his story didn’t end there. Not long after being discharged, he needed to get his big toe amputated, but the medical team couldn’t use a general anesthetic because of his health, and it would need to be done using a regional block. This caused him to spiral into a panic attack, until he agreed to use VR to calm his nerves, allowing the operation to continue.”

Summary

Pain management has been troubled by its subjective nature, where simply treating the ‘problem’ doesn’t always equate to therapeutic success. This can leave patients with enduring pain and anxiety, and clinicians with few options. The call for novel therapies to fill the gap in managing pain is being answered with the help of extraordinary innovations stemming from the healthtech sector, which are nurtured in thriving hubs such as Basel. Although there is no silver bullet, neuroplasticity training and VR are now additional tools in the clinician’s armamentarium, allowing them to not only reach for their pharmacopeia, but also turn to technology to help improve the lives of their patients in pain.

References
1. Cohen S, Vase L, Hooten W. Chronic pain: an update on burden, best practices, and new advances. The Lancet. 2021;397(10289): 2082- 2097. doi: https://doi.org/10.1016/S0140-6736(21)00393-7
2. Yeung A, Tosevska A, Klager E, et al. Virtual and Augmented Reality Applications in Medicine: Analysis of the Scientific Literature. J Med Internet Res. 2021;23(2):e25499.  doi: https://doi.org/10.2196/25499
3. Rescape. The Evidence for Virtual Reality in the Clinic. 2021. https://www.rescape.health/virtual-reality-white-paper [Accessed 10 July 2023]
4. Gupta A, Scott K, Dukewich M. Innovative Technology Using Virtual Reality in the Treatment of Pain: Does It Reduce Pain  via Distraction, or Is There More to It? Pain Med. 2018  Jan 1;19(1):151-159. doi: https://doi.org/10.1093/pm/pnx109. PMID: 29025113.