The chronic pain puzzle – Is DBS the missing piece?

Pain – and how we approach it – is a perpetual puzzle for all member of our health-care system. Physicians scratch their heads in finding ways to prevent pain and treat that which persists after their patients leave the hospital, but this is an uphill battle. Those who continue to experience pain have earned contracts for a lifelong journey with their pain. Chronic pain, especially back pain, contributes more than $500 billion to annual health-care costs [1] and disables more than 20% of the workforce [2]. However, many potential solutions are themselves expensive puzzle pieces that can be misunderstood or incompatible with the patients they attempt to treat.

Prescription painkillers, or “opioids,” while touted as a cheap and effective therapy for many different kinds of pain, have consistently made headlines because of the rapid increase in narcotic-related deaths over the past decade. [3] However, they are not without their side effects, which are not uncommon – more than 20% of patients will experience constipation, nausea, and itching, and over-sedation. Higher-risk patients may experience breathing issues, especially if they have been receiving similar medications or have medical problems that prolong the effects of these pills. A recent CDC survey reported that a quarter of patients with legitimate prescriptions are incorrectly using or storing these medications, increasing the risk for overdose or harm to their loved ones in close proximity. [4]

The crisis has called for physicians and researchers to work ever so closely together to produce alternative treatments that are effective in patients that are nowadays living longer with more complex medical problems.

One of these therapies include deep brain stimulation (DBS) therapy, a treatment modality that has long been studied and evaluated for use in several brain-related disorders. Since the 1970s, scientists have discovered specific “targets” within the brain that conduct irregular patterns of brain electrical activity, and these patterns have been associated with different pain syndromes. Initial interest in this technology focused on the use of DBS to treat movement disorders, including Parkinson’s Disease. Many movement disorders are associated with pain itself, and patients reported an increase in their quality of life and pain control with further improvements in the procedure over time.

In the past 30 years, collaborations between neurosurgeons, pain specialists, and researchers led to its use in patients with chronic pain syndromes, with significant success with patients with cluster headaches and back pain. [5] Current research is exploring its use in pain after stroke or loss or a limb (e.g. phantom limb pain) [6]. Treatment effect is even more significant with patients who have previously failed to realize adequate pain relief with escalating conventional treatments methods, including:

1) over-the counter medications (e.g. Tylenol, Advil)

2) prescription opioid therapy

3) neuropathic pain treatments (e.g. Neurontin, Lyrica)

4) complementary therapies (e.g. acupuncture),

5) interventional pain therapies (e.g. injections for nerve block, radiofrequency and chemical denervation).

It is natural to have questions about the overall safety and approach of this “brain surgery.” After a referral to a neurosurgeon with specialized experience, patients receive routine pre-operative medical and surgical evaluations, including a thorough review of pain complaints, triggers, and expectations for eventual relief. On the day of the procedure, the patient is placed under general anesthesia, and a small device called a pulse generator (e.g. neurostimulator) in is placed in the neck or abdomen. Leads connect the generator to the “target” areas in the brain, and the integrity of the connections and the generator are tested before the end of the procedure. Recovery in the hospital lasts a few days, and the patient may receive closer (i.e. around-the-clock) monitoring for the first 24 hours for unlikely complications including bleeding, infection and seizures. After leaving the hospital, a few patients may report slight changes in mood and personality. DBS lead placement may be responsible for the majority of these complaints, and it is very important to follow-up with the surgeon within 1-2 weeks after the initial procedure.

DBS has proven to be beneficial for patients with the most recalcitrant types of pain. In combination with conventional and alternative treatments (e.g. multimodal therapy), DBS provides an essential piece of the pain puzzle that may be beneficial with other pain syndromes and clinical disorders syndromes in the future.


References

[1] Institute of Medicine Report from the Committee on Advancing Pain Research, Care, and Education: Relieving Pain in America, A Blueprint for Transforming Prevention, Care, Education and Research. The National Academies Press, 2011. http://books.nap.edu/openbook.php?record_id=13172&page=1.

[2] Peter D. Hart Research Associates. Page 3. KEY FINDINGS. Americans in Pain. Much of America is hurting: the majority of adults (57%) in this country have … http://www.researchamerica.org/uploads/poll2003pain.pdf

[3] Vivolo-Kantor AM, Seth P, Gladden RM, et al. Vital Signs: Trends in Emergency Department Visits for Suspected Opioid Overdoses — United States, July 2016–September 2017. MMWR Morb Mortal Wkly Rep 2018;67:279–285. DOI: http://dx.doi.org/10.15585/mmwr.mm6709e1

[4] QuickStats: Percentage of Emergency Department Visits That Had an Opioid Ordered or Prescribed, by Age Group — National Hospital Ambulatory Medical Care Survey, United States, 2006–2015. MMWR Morb Mortal Wkly Rep 2018;67:344. DOI: http://dx.doi.org/10.15585/mmwr.mm6711a8

[5] Lempka SF, Malone DA, Hu B, Baker KB, Wyant A, Ozinga JG, Plow EB., Pandya M, Kubu CS, Ford PJ, Machado AG. Randomized clinical trial of deep brain stimulation for poststroke pain. Ann Neurol. 2017 May;81(5):653-663. doi: 10.1002/ana.24927.

[6] Bittar, RG. et al. Deep brain stimulation for pain relief: A meta-analysis. J Clin Neurosci. 2005 Jun;12(5):515-9. DOI:10.1016/j.jocn.2004.10.005

A Promising Treatment for Neurological Disease and Psychiatric Disorders

Neuromodulation or Neurostimulation is a promising modality for treating neurological disease (Parkinson’s disease, Tremors, Chronic Pain, seizures) as well as psychiatric disorders (Major Depression, OCD). The basic premise of neuromodulation is that by stimulating deep brain structures, it is possible to disrupt abnormal patterns of brain activity (in people with neurologic disease) and thereby restore normal brain electrical rhythms resulting in improvement and even resolution of symptoms. While the exact mechanism of how Neuromodulation works is not completely understood, it is believed that restoring normal brain electrical activity is essential to improve disease symptoms. Contrary to what many in the general public would think, a typical neurostimulating system is relatively simple in that it consists of only three components: an implantable stimulator generator/pulse generator (IPG), a lead, and extension wiring. Traditional Neuromodulation consists of continuous high-frequency stimulation (known as an open-loop system). While effective in minimizing some symptoms, this method of neuromodulation comes with the drawbacks of causing potential tissue damage from the constant stimulation as well as shortening generator (IPG) battery life to 2-5 years.

In continuous pursuit of a cure, neuromodulation companies/labs are developing increasingly sophisticated brain stimulators. Building off the success of the open-loop system, researchers have developed next generation systems that make stimulation more targeted not only in terms of where, but when stimulation occurs. This new targeted type of therapy where stimulation occurs in response to specific changes in a patient’s electrical brain activity is known as closed-loop neuromodulation. These implantable devices are able to record the electrical activities of many neurons continuously and as a result, determine patterns in the overall neural activity. The specific neural patterns are then able to be utilized as an input signal to the processor in the device that can sync neurostimulation with a specific event.

Consider that an early usage for neuromodulation was treating refractory epilepsy, an event that occurs spontaneously and unpredictably (much like that of a life-threatening cardiac arrhythmia). One could see the similarities between a neuromodulator and Automated Implantable Cardioverter Defibrillator (AICD), and thus the benefits provided by a closed-loop system. Much like how an AICD delivers a shock to stop an abnormal heart rhythm only when it occurs, an implantable closed loop neurostimulator can halt an epileptic seizure by delivering stimulation when it senses the beginning of seizure activity in the brain. While only an analogy, it makes sense that a device that only as beneficial in specific situations would be better to be triggered for that purpose alone.

The transformational benefit of closed loop neuromodulation clearly is a targeted therapy specific to an individual’s electrical brain activity, but other benefits of a closed loop system are still impressive such as a potential decrease in tissue damage as well as an overall decrease in power consumption leading to increased battery life (and subsequently avoiding frequent surgical IPG replacement). The benefits of the closed loop system are now starting to be quantified with early studies are demonstrating promising results with the treatment of epilepsy. A 2018 FDA approved study demonstrated that patients with a closed loop system experienced a 70% median seizure reduction after five years of therapy. This finding as well as numerous other promising ones are validating the benefits of a closed loop system. As a result of its individualization, closed loop neuromodulation can and is now being applied to all types of neuropathology. As the technology continues to be refined the benefits to those suffering will only increase.