Jun 22 2021

Brain Implant to Treat Pain

Researchers report a study in which they investigate the potential of a closed loop brain-machine interface (BMI) to treat pain in rats. If this line of research is successful it could lead to a new paradigm in the management of chronic pain.

Chronic pain is a tricky condition to treat because we currently have limited options, all of which are problematic in some way. Acute pain, such as after trauma or surgery, is easier to manage because the treatment course is likely to be limited. This kind of pain is called nociceptive pain, when it is the result of tissue damage. The obvious goal here is to manage the damage by treating the underlying condition, but manage the pain in the meantime until healing can reduce the pain. Another category of pain is terminal pain, such as in some cancer patients. While this has its own challenges, aggressive pain management is also appropriate.

Chronic pain, however, may need to be sustained for years, and this presents serious challenges. This may be due to chronic conditions that cannot be cured, such as arthritis, degenerative changes, and primary pain conditions like migraines. This category also include neuropathic pain, where the pain is due to abnormalities in the nervous system itself, rather than the nervous system properly detecting tissue damage. With neuropathic pain, the pain itself is often the disorder.

The challenges of chronic pain stem from the fact that it is often difficult to find a treatment that is effective. But also, even if a treatment is effective, pain medication itself (analgesics) has risks from long term use. Aspirin-like drugs (NSAIDS) can cause ulcers and kidney damage. Acetaminophen can cause liver damage. Narcotics are addictive and cause tolerance. The best approach to chronic neuropathic pain is what we call neuropathic pain prophylaxis – medications safe and intended to take daily to reduce overall pain. But these medications can have significant side effects, and don’t always work sufficiently. There are also nerve stimulators, which avoid pharmaceutical side effects, but have limited efficacy.

With all of these options, however, for most patients we can make a significant improvement in their pain and quality of life. But it can be challenging, and some patients don’t respond adequately to existing treatments. So more options are always welcome.

The idea of using electrical or magnetic stimulation to affect nerve or brain function is therefore an attractive option. The advantage is that these interventions can directly affect brain function while avoiding pharmaceutical risks and side effects. The downside is that such interventions can be invasive and the technology is still in its infancy.

The current study is therefore an important proof of concept, but of course is preliminary, partly because it was conducted in rats. The researchers implanted a computer chip in the frontal cortex of rats. This is a closed-loop system, which means it reads brain activity in order to control its stimulating effect. In this case the chip reads activity from the anterior cingulate cortex, which is involved in pain perception. However, it not only detected activity but interpreted that activity to judge when pain specifically was being perceived. According to the researchers their device was 80% accurate in detecting pain. The chip also connected to an area of the prefrontal cortex which inhibits pain, and it stimulated this region when it detected pain from the cingulate cortex.

The researchers used two standard methods to determine the effects. One is to present a painful stimuli to the rats’ paws (like slowly increasing temperature) and measure how quickly they withdraw. In this study the rats with the stimulator on withdrew 40% more slowly than with the stimulator off. They also kept the rats in a cage with two chambers, on in which the stimulator is on and the other off, and the rats spent twice as much time in the chamber with the stimulator on.¬†Obviously this will have to be checked in human subjects to determine its actual efficacy, but this is a good proof of concept.

Just because this method uses brain stimulation rather than drugs does not mean there is not issue with chronic use. The part of the brain stimulated should not produce any euphoria or activate the reward centers, so hopefully this will not cause any addiction phenomenon. But the brain can still habituate to chronic stimulation. This means that the stimulator may become less effective over time. Also, if chronic stimulation downregulates the prefrontal cortex being stimulated this may actually increase baseline pain over time, by reducing baseline inhibition. Again, this will have to be studied before this becomes an accepted treatment.

Brain-machine interface technology is improving overall, and interventions like this are likely to benefit from generic improvement in the technology. Stimulating specific parts of the brain is likely to be a more precise intervention than any drug, because the brain tends to share neurotransmitters and receptors for different functions. But if you can isolate one circuit, then you can isolate one function. Further, a closed-loop approach can deliver or inhibit stimulation based on moment-to-moment needs. This could reduce the overall “dose” of the intervention. Algorithms might also theoretically be developed to minimize habituation. Rather than depending on the patient, whos is in pain, to follow strict protocols to minimize adverse effects, these protocols can be built into the treatment itself.

No one treatment is likely to be a panacea, but we are potentially seeing the opening up of a new approach to brain therapeutics that could potentially have higher efficacy and safety and fewer side effects. As always, though, be patient. I suspect we are 10-20 years away from advanced applications like this.

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