Neurological

Deep Mind Stimulation: The Reply To Continual Ache?

Chronic pain affects 1 in 4 adults in the US, many of whom are drug-resistant.1 It places a significant burden on individuals and health systems, affecting mental health, cognitive function, and the promotion of opioid addiction.2 However, researchers are short before discovering new ways to treat the disease – including through deep brain stimulation (DBS).

What is DBS?

DBS has the potential to treat a variety of neurological disorders by implanting electrical electrodes in specific areas of the cerebral cortex or subcortex and connecting the electrodes to an implanted electrical stimulator.3 Electrically stimulated areas of the brain are then stimulated to relieve certain symptoms or eliminate. While this treatment strategy is approved for motor disorders such as essential tremors, dystonia, and Parkinson’s disease, it is gaining increasing interest for pain relief in therapy-resistant individuals

DBS for the treatment of chronic pain

Since the 1950s, researchers have studied DBS as a treatment for those with incurable, pain-causing disorders.5 These studies have included a variety of difficult-to-treat pain syndromes ranging from brachial plexopathy to spinal cord injury and thalamic pain syndrome to accidental-related pain and mechanical lower pain Back area.6 Success has also been reported for incurable facial pain, although subsequent studies targeting various chronic pain disorders have shown inconsistent effectiveness.5,6 Consequently, DBS is still viewed as investigative and “off-label” for chronic pain treatment today.

However, this off-label status has not hampered research. One study reported the results of 59 patients with various chronic pain syndromes who received DBS in the periventricular gray area (PVG) of the brain and / or thalamus.7 Compared to the preoperative values, the results showed a dramatic improvement, with more than that Half of the patients reported pain relief of 50 percent regardless of the pain etiology.

Another study involved performing DBS in the periaqueductal gray (PAG) or PVG area, as well as in the sensory region of the thalamus or inner capsule in patients with various causes of pain. The pain reduction was over 50 percent. 8

Interestingly, some patients who do not meet the 50 percent pain reduction criteria so widely used in research say that they are very satisfied with any pain reduction because it significantly improves their quality of life.9 This means that many patients have been shown to have failed DBS -Treatment independent of a partial but notable improvement.

Identifying new destinations for chronic pain management

Prasad Shirvalkar, pain doctor and assistant professor at the University of California, explains: “Historically, DBS has primarily targeted two brain regions: the ventral thalamus and the PAG areas. Thalamic DBS was believed to work in accordance with the gate control theory of pain. Stimulation of the thalamus is believed to produce a tingling sensation or other paresthesia that effectively blocks pain-related transmission of fibers that provide inputs from the periphery and the spinal cord. Gate control theory assumes that ascending fibers / inputs into the brain have limited bandwidth and that providing additional inputs can disrupt pain signal transmission. The PAG DBS can help by strengthening the body’s own opioid system, but there is some controversy about this. “3

Research suggests that a low frequency below 50 Hz has an analgesic effect on thalamus and PAG stimulation, while higher frequencies above 70 Hz are believed to increase pain sensitivity. Additionally, stimulation of the ventral posterolateral (VPL) and ventral posteromedial (VPM) nuclei causes a comfortable sensation that overrides the pain, while stimulation of the PVG and PAG areas induces analgesia and a warm sensation over the painful region. 9

“More recently, a team at Oxford introduced DBS of the anterior cingulate cortex (ACC), which can reduce the ‘discomfort’ or ‘annoyance’ of pain without affecting the somatosensory component of pain,” says Shirvalkar. Patients have reported that while the pain was not completely relieved, it was less irritating or felt removed from it, demonstrating the emotional or affective aspect of the ACC.9

Overcoming obstacles to the effective use of DBS

DBS currently involves a constant flow of electricity and does not adapt to changes in brain activity.1 According to Shirvalkar, “one of the biggest obstacles in DBS against pain is that DBS often loses its effectiveness in the long term, regardless of which target is stimulated Years for many patients. That is, the brain seems to adapt to the stimulation and “ignore” it. We are trying to figure out how to overcome such an adjustment. “3

“It is more likely that multiple regions of the brain will join together in a network to create and maintain chronic pain conditions,” explains Shirvalkar. “We are conducting a clinical study that includes a novel test period in which patients temporarily place electrodes in their brain for a period of 10 days. We then work very hard over 10 days to record brain activity and stimulate multiple regions that we believe are important for chronic pain. In this way, we can determine which areas, or “knots”, will be the most pain reliever when stimulated for that individual. “By conducting a comprehensive test phase, Shirvalkar and his team can learn more about the network behavior of chronic pain in the brain and maximize the likelihood of finding an effective therapy for each patient. Importantly, Shirvalkar says, “This way, patients will not be implanted with a permanent device when the likelihood of long-term benefit is low.”

Any emerging research could advance treatment for other conditions as well. “Other brain diseases that are treated with brain stimulation, such as epilepsy, Parkinson’s and depression (although experimental), could also benefit from developing technology that would make the stimulation respond to sustained neural activity,” says Shirvalkar. “Many of my colleagues are working on developing an adaptive DBS for these other conditions.”

The future of DBS in chronic pain

Go forward, Shirvalkar believes that advances are needed in two important scientific areas. “The first is understanding the basic brain mechanisms underlying these diseases so that we can better understand what effects stimulation actually has on the disease itself,” he says. “The second is to find out how we can non-invasively modulate key brain circuits using transcranial magnetic stimulation or scalp stimulation. I think the future is moving away from stimulating individual brain regions towards networks, ultimately with the aim of doing this without invasive implants. ”

References

1. Miller, YES. Tailored deep brain stimulation for the treatment of chronic pain. UC San Francisco. Published on February 3, 2020. Accessed December 20, 2020. https://www.ucsf.edu/news/2020/02/416601/tailoring-deep-brain-stimulation-treat-chronic-pain.

2. Dydyk AM, Yarrarapu SNS, Conermann T. Chronic pain. StatPearls; 2020. Updated November 8, 2020. https://www.ncbi.nlm.nih.gov/books/NBK553030/

3. Shirvalkar P., Sellers KK, Schmitgen A. et al. A test phase of deep brain stimulation for the treatment of chronic pain. J Clin Med. 2020; 9 (10): 3155. doi: 10.3390 / jcm9103155

4. Lozano AM, Lipsman N., Bergman H. et al. Deep brain stimulation: current challenges and future directions. Nat Rev Neurol. 2019; 15 (3): 148-180; 160. doi: 10.1038 / s41582-018-0128-2

5. Frizon LA, Yamamoto EA, Nagel SJ, Simonson MT, Hogue O, Machado AG. Deep Brain Stimulation for Pain in Modern Times: A Systematic Review. Neurosurgery. 2020; 86 (2): 191-202. doi: 10.1093 / neuros / nyy552

6. Ben-Haim S., Mirzadeh Z., Rosenberg WS. Deep brain stimulation for persistent neuropathic facial pain. Neurosurgical focus. 2018; 45 (2): E15. doi: 10.3171 / 2018.5.FOCUS18160

7. Boccard SGJ, Pereira EAC, Moir L., Aziz TZ, Green AL Long-term results of deep brain stimulation in neuropathic pain. Neurosurgery. 2013; 72: 221–2 230. doi: 10.1227 / NEW.0b013e31827b97d6

8. Kumar K, Toth C, Nath RK Deep Brain Stimulation for Persistent Pain: A 15 Year Experience. Neurosurgery. 1997; 40: 736- 746. doi: 10.1097 / 00006123-199704000-00015

9. Farrell SM, Green A, Aziz T. The current state of deep brain stimulation in chronic pain and its context in other forms of neuromodulation. Brain Sci. 2018; 8 (8): 158. doi: 10.3390 / brainsci8080158

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