Worldwide, 1.5 billion people live with chronic pain, with greater prevalence among adults living in poverty, women and the elderly. In the US alone, chronic pain costs an estimated $560–635 billion per year in direct medical costs, lost productivity and disability programmes. Treatment for pain remains a major scientific and clinical challenge: the current portfolio of analgesic drugs such as opioids can relieve pain, but they also have immediate side effects on sensory and mental function and carry the risk of long-term addiction.
That is why researchers at Lund University, led by neurophysiology professor Jens Schouenborg, have developed a method to combat pain via personalized stimulation using micron-thin, tissue-friendly microelectrode arrays. They publish their study in Science Advances.
“We have achieved an almost total blockade of pain without affecting any other sensory system or motor skill, which is a major breakthrough in pain research. Our results show that it is actually possible to develop powerful and side-effect-free pain relief, something that has been a major challenge up to now,” explains Matilde Forni, doctoral student and first author of the new pain-relief study.
Tissue-friendly microelectrode technology
The technique applies electrical stimulation deep inside the brain to two regions called the periaqueductal grey substance (PAG) and dorsal raphe nucleus (DRN). Both the PAG and the DRN are part of the brain’s pain control centres, which makes them key targets for pain-relief treatments. While deep-brain stimulation has been attempted before to relieve pain, previous studies have had variable success due to foreign-body reactions to the electrode technology, which led to loss of local neurons and reduced stimulation efficacy.
To address these limitations, the team developed a highly flexible cluster of microelectrodes coated in hard gelatin needles. The gelatin expands and then dissolves during implantation, enabling insertion of the ultrathin microelectrodes and high-precision stimulation of deep-brain targets with minimal damage to nerves.
“We have been working for more than a decade on developing tissue-friendly technology that can sit in the tissue without irritation,” explains Schouenborg.
The cluster design of the microelectrodes enables a personalized pain treatment approach, as specific subgroups of electrodes can be activated and modulated to provide pain relief to suit an individual’s needs. The researchers tested their procedure on rats and found that electrical stimulation remained effective in treating pain using the same microelectrode subset and stimulation parameters for 11 weeks of testing, showing the high stability of the implanted microelectrodes for long-term pain analgesia. They did not observe visible side effects during the course of treatment, indicating that the technology provided pain relief without causing adverse reactions.
Novel animal model enables pain quantification
The researchers also developed an animal model in which the degree of pain signal could be quantified, enabling them to validate the treatment efficacy. Using a similar cluster recording array, they detected these pain signals in the rat’s brain. “We combine reading out the pain signal to the cortex cerebri with conventional reflex tests, so it’s a much more valid animal model for pain,” says Schouenborg.
The team compared their new technology with morphine-induced pain relief. “The technology was clearly superior,” states Schouenborg, highlighting that the novel stimulation technology yielded stronger analgesia than morphine (as seen through a reduction in pain signal) while at the same time having little to no adverse side effects.
Future of electrical stimulation in brain disease therapeutics
Schouenborg imagines a future where high-efficacy pain treatment can be delivered on demand, depending on the patient’s pain levels. Taking this a step further, patient-controlled interfaces could allow the patient to activate stimulation when they start to feel pain. The team’s current goal is to scale this treatment system up for humans within the next five to eight years. If further validated in humans, the technology could provide greater pain relief than drugs for those suffering from severe pain who currently have no satisfactory treatment.
Ultralow-frequency neuromodulation safely relieves chronic pain
According to the researchers, the technology could also be employed to treat other neurological conditions. “We recently published a study on a Parkinson’s disease model where we used very similar technology, which in that case restored normal motor movements with no side effects,” Schouenborg explains. In this study, they implanted the cluster technology in the part of the brain that regulates movement. Using personalized stimulation parameters, the team provided powerful, specific therapeutic effects in rat models. They claim that this treatment for Parkinson’s will be ready to test in the first humans within the next two years.
The team anticipates that this technology could demystify currently unknown details about how the brain operates. Through being able to both stimulate and record output signals of relevant brain regions; their technology could enable the development of improved diagnostics for a series of brain diseases.
