The Future of Pain Control
The Rise and Fall of Pain Treatment
In addition to developing treatments to address pathology and disease, the evolution of neurosurgery has been closely tied with innovations that alleviate pain and suffering. Some seminal examples that have included a longstanding impetus for technological advancement are:
- Walter Dandy’s early work on trigeminal rootlet sectioning and lumbar discectomy
- Peter Janetta’s use of the operative microscope in developing microvascular decompression
- Akil and Richardson’s development of deep brain stimulation
While neurosurgeons sought techniques to treat pain without medications, several concepts drove the use of opioids over the last two decades. One was the mistaken propagation of the idea that patients do not become addicted to opioids when used for pain. This was further exacerbated by the adoption of pain as the “5th vital sign” in the mid-1990s. As a result, patients were referred for other treatments, including neurosurgical ones, only after “failed” pharmacologic therapy with opioids. Increased opioid prescribing initially addressed the demand to control acute pain, but the prevalence of runaway opioid use clarified its significant downsides, including:
- Hypogonadism leading to osteoporosis
- Extreme difficulty controlling acute pain
- Opioid-induced hyperalgesia
- Decreased efficacy of later interventions for pain
- Overdose and death
Now the tide has turned and federal and state governments are more invested in legislation to reduce opioid use. It is essential that neurosurgeons are armed with data to support best practices for surgical interventions and to advocate for patients who can benefit from opioids beyond regulatory restrictions that are not evidence-based.
Individual neurosurgeons can implement multimodal therapy and multidisciplinary consideration of neurosurgical treatments, including use of spinal surgery, spinal cord stimulation and ablative procedures. The International Association for the Study of Pain (IASP) has multimodal treatment guidelines for both acute pain and neuropathic pain2, which can be integrated into electronic medical record phrases for easy access to evidence-based recommendations. For patients undergoing surgery, initiation of multimodal pre-operative medication protocols (including gabapentin, magnesium, vitamin C, acetaminophen and nonsteroidal anti-inflammatories) all demonstrated significant pain reduction in the peri-operative period. Our neuro-anesthesia colleagues have studied the impact of their medication choices on post-operative pain, with some studies showing significant benefit with the use ketamine and dexmedetomidine during and even after surgery.3
The development of enhanced recovery after surgery (ERAS) protocols has proven remarkably effective in many types of surgeries, but presents a challenge in a neurosurgical patient population. Successful ERAS implementation has been reported in minimally invasive,4 complex5 and oncologic6 spine programs. Streamlining of patient care with the use of ERAS protocols increases staff empowerment, efficiency and adherence to post-operative goals, like early ambulation. Multimodal pain regimens can be integrated into these ERAS protocols as well.
Moving Toward the Future
Our conceptualization of pain related to the spine has evolved from a focus on neural decompression alone to include treatment of pain generated from mechanical instability and biomechanical imbalances. Similarly, neuromodulation, including spinal cord stimulation (SCS), has gone beyond the idea that stimulation needs to induce paresthesias in the affected area to be effective. Newer stimulation paradigms, such as high frequency stimulation, may prove more effective through a complex mechanism of blocking the inhibitory signals in a specialized area of the spinal cord (the dorsal horn of the spinal cord).7 This results in limiting the transmission of pain signals up to the patient’s consciousness. As the efficacy of SCS improves, it will serve to:
- Enlarge the population of patients who can be treated via an opioid-sparing intervention.
- Work as an alternative to extensive spinal surgeries that have long recoveries in patients without progressive neurological deficits that necessitate neural decompression.
- Salvage those who have lost responsiveness from their systems.
Additionally, wireless microtechnology for stimulation of the spinal cord, peripheral nerves or the dorsal root ganglion without expensive internal pulse generators may make this technology available to new populations around the world.
While the paradigms described above offer a spectrum of real-world, currently implementable options, technologies forecasted for the next 10-20 years may be truly practice-changing. Here are a few tantalizing possibilities:
- Utilizing advanced neuroimaging incorporating PET9 and tractography10 may better identify target subpopulations who are likely to benefit from neuromodulation and effective anatomic targets rendering DBS a viable treatment for some pain patients. This should then eclipse the marginal results seen in previous trials at Deep Brain Stimulation (DBS) for pain.
- MR-guided focused ultrasound to induce a temporary lesion may serve as a revolutionary tool for testing hypotheses in humans in a low-risk, minimally-invasive manner11.
- Variations in arrangement of the electrode array allow for new fields of stimulation to maximize the efficiency of the system.
- Closed loop systems have the potential for machine learning that may recognize, identify or refine physiologic targets for stimulation to reduce pain.
Similar to deep brain targets, advances in cortical stimulation are also possible. Cortical stimulation and non-invasive modalities, like transmagnetic and transcranial direct current stimulation, have been shown to be effective in relieving pain.12 Furthermore, similar to responsive neurostimulation used in epilepsy, integration of closed loop stimulation of the motor cortex via epidural or subdural strip or grid arrays could refine stimulation.
The Brain and the Heart
One of the difficulties in treating pain is the emotional overlay that can exacerbate pain. Deriving novel interventions for this component of pain management may prove invaluable. Many patients who fail multimodal therapy with biofeedback and cognitive behavioral therapy, may ultimately benefit from modulation of targets within the limbic circuitry, including the anterior cingulate, hypothalamus and ventral striatum.13
Yet another area ripe for evolution is development of a more quantitative and objective analysis of pain. Capacity in this is severely limited and further aggravates situations in which socioeconomic factors lead to exaggeration of pain, as in cases of disability and workman’s compensation. The National Center for Advancing Translational Sciences recently released a funding opportunity (NOT-TR-19-007) for tissue chips to model nociception, addiction and overdose. These microphysiological systems, or “tissue chips,” could record and model the biochemistry of nociceptive signaling, help to discover translatable biomarkers, test the biochemical efficacy of medications in development and/or objectively measure patients’ individual responses to medications.
2030: A New Pain Paradigm
Envision this scenario:
- Opioids are scarcely used; addiction and overdose are virtually unheard of.
- Pain is prevented through understanding aging and biology better.
- Surgical interventions have vastly improved, leading to considerably less post-operative pain issues.
- Patients suffering from pain can be truly understood through microchip and neurophysiological analysis.
- One of a host of SCS, DMS or noninvasive interventions are applied to return the pain patient to an active, productive quality of life.
This is indeed possible. As has historically been the case, advancements championed by neurosurgeons are likely to lead the way in advancing the treatment of pain and obtaining this appealing scenario.
1. Porter, J., & Jick, H. (1980). Addiction Rare in Patients Treated with Narcotics. New England Journal of Medicine, 302(2), 123.
2. IASP Guidelines. (2018). Retrieved from https://www.iasp-pain.org/Guidelines?navItemNumber=648
3. Dunn, L. K., Durieux, M. E., & Nemergut, E. C. (2016). Non-opioid analgesics: Novel approaches to perioperative analgesia for major spine surgery. Best Practice & Research Clinical Anaesthesiology, 30(1), 79-89.
4. Soffin, E. M., Vaishnav, A. S., Wetmore, D., Barber, L., Hill, P., Gang, C. H., . . . Qureshi, S. A. (2018). Design and Implementation of an Enhanced Recovery After Surgery (ERAS) Program for Minimally Invasive Lumbar Decompression Spine Surgery. Spine, 1.
5. Lamperti, M., Tufegdzic, B., & Avitsian, R. (2017). Management of complex spine surgery. Current Opinion in Anaesthesiology, 30(5), 551-556.
6. Grasu, R. M., Cata, J. P., Dang, A. Q., Tatsui, C. E., Rhines, L. D., Hagan, K. B., . . . Popat, K. U. (2018). Implementation of an Enhanced Recovery After Spine Surgery program at a large cancer center: A preliminary analysis. Journal of Neurosurgery: Spine, 588-598.
7. Kwan, Y. L. (2018).High Frequency kHz Spinal Cord Stimulation (SCS) Differently Affects Rodent Superficial Dorsal Horn Cell Types.
8. Coffey, R. J. (2001). Deep Brain Stimulation for Chronic Pain: Results of Two Multicenter Trials and a Structured Review. Pain Medicine, 2(3), 183-192.
9. Mayberg, H. S., Lozano, A. M., Voon, V., Mcneely, H. E., Seminowicz, D., Hamani, C., . . . Kennedy, S. H. (2005). Deep Brain Stimulation for Treatment-Resistant Depression. Neuron, 45(5), 651-660.
10. Riva-Posse, P., Choi, K. S., Holtzheimer, P. E., Crowell, A. L., Garlow, S. J., Rajendra, J. K., . . . Mayberg, H. S. (2017). A connectomic approach for subcallosal cingulate deep brain stimulation surgery: Prospective targeting in treatment-resistant depression. Molecular Psychiatry, 23(4), 843-849.
11. Schwalb, J. M. (2013). Letters to the Editor: Magnetic resonance–guided focused ultrasound surgery. Journal of Neurosurgery, 119(2), 531-531.
12. Moisset, X., & Lefaucheur, J. (2018). Non pharmacological treatment for neuropathic pain: Invasive and non-invasive cortical stimulation. Revue Neurologique.
13. Keifer, O. P., Riley, J. P., & Boulis, N. M. (2014). Deep Brain Stimulation for Chronic Pain. Neurosurgery Clinics of North America, 25(4), 671-692.
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