Currently available pharmacological and nonpharmacological options are still ill-adapted to the treatment of chronic pain, rendering treatment of this heterogenous and common condition challenging.
Social and economic challenges associated with opioid analgesics, widely used to manage chronic pain, have driven the search for alternative pain treatment modalities. This has included the identification of new targets for peripherally restricted opioid analgesics.
In the search for new modalities for chronic pain management, neurostimulation, a minimally invasive and reversible technique that delivers low level electrical signals to the brain, spinal cord and peripheral nerves, appears as an increasingly attractive option. With this modality, relief is achieved by modulating the transmission of pain messages to the brain.
Several neurostimulation devices are available globally. A device for spinal cord stimulation (SCS) which was FDA-approved in 1989, is now considered a standard treatment for patients with chronic back pain that is not relieved by other treatments.1
Peripheral nerve field stimulation (PNFS) is based on the same principle as SCS, but requires a surgical procedure. While PNFS devices are yet to receive FDA approval, their efficacy in managing chronic low back pain has been demonstrated in small scale studies.2-4 As evidence supporting the use of neurostimulation for a number of chronic pain conditions was unclear, the European Federation of Neurological Societies (EFNS) launched a Task Force focused on evaluating its efficacy.
Based on a systematic review of the literature, the EFNS published in 2007 guidelines on neurostimulation therapy for neuropathic pain.5 Recommendations were made for the use of SCS in failed back surgery syndrome (FBSS) and complex regional pain syndrome (CRPS) type I. However, the EFNS guidelines were restricted to neuropathic pain, and controlled trials supporting neurostimulation in other chronic pain conditions were lacking.
With the increasing and popular use of neurostimulation devices for various chronic pain conditions, the International Neuromodulation Society (INS) convened the Neuromodulation Appropriateness Consensus Committee (NACC) to review and assess the quality of the scientific and medical literature, and in 2014, published several consensus recommendations on the appropriate use of neurostimulation for the management of chronic pain.6-9
These recommendations emphasize that, while neurostimulation is effective in some chronic pain conditions, the field is rapidly evolving with continual improvement of existing technologies and emergence of new clinical evidence. The European Academy of Neurology (EAN) therefore recently published updated guidelines on central neurostimulation therapy for chronic pain.10
“As technologies progress and indications expand, practice guidelines help physicians assimilate and apply new knowledge about efficiency, efficacy and safety so they may exercise their best clinical judgment about existing and emerging medical interventions,” said Timothy Ray Deer, MD, DABPM, Chairman of the NACC, President-Elect of the INS, and chief executive officer of The Center for Pain Relief, Inc. in Charleston, West Virginia.”
Simon Thomson, MBBS, FFPMRCA, president of the INS, added “we believe that securing access to neurostimulation treatments for selected patients with chronic pain administered by appropriately trained practitioners is an important challenge to all health economies … an expert consensus should help to avoid issues of underuse, overuse, or misuse.”11
The EAN guidelines are based on a systematic review and meta-analysis of clinical trials published between 2006 and 2014. The analysis was designed to answer specific questions related to the appropriate and optimal application of commonly used neurostimulation techniques.
Techniques reviewed included SCS, deep brain stimulation (DBS), epidural motor cortex stimulation (MCS), repetitive transcranial magnetic stimulation (rTMS) and transcranial direct electrical stimulation (tDCS) of the primary motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC), for the treatment of pain conditions including neuropathic pain, fibromyalgia, complex regional pain syndrome (CRPS) type I and post-surgical chronic back and leg pain (CBLP).
Across all the neuromodulation techniques evaluated, the evidence supports weak recommendation for the use of SCS with conventional medical management for painful diabetic neuropathy, CLBP, CRPS 1, and as an alternative to reoperation in postsurgical CBLP.
Similarly, the evidence is weak for the use of MCS in neuropathic pain, rTMS, of M1 in neuropathic pain and fibromyalgia, and of tDCS of M1 in neuropathic pain. The evidence is however, inconclusive for DBS in neuropathic pain, rTMS and tDCS of the DLPFC and for motor cortex and for tDCS in fibromyalgia and spinal cord injury pain.
Neurostimulation is a rapidly evolving field and new techniques are emerging. For example, high frequency or burst SCS, dorsal root ganglion stimulation, and H-coil rTMS are advanced techniques that may improve patient experience as well have extended reach for pain control.12-14
It is therefore essential to demonstrate safety and efficacy of all neurostimulation techniques with robust scientific evidence so as to ensure appropriate use of these potentially useful modalities and avoid underuse, overuse or misuse.
Summary and Clinical Applicability
Neurostimulation is an increasingly used technique for chronic pain management. The lack of evidence base on which these devices are used for different pain conditions resulted in the development of guideline recommendations based on systematic review and meta-analysis of published studies.
Overall, there is poor quality of evidence to support the use of currently available neurostimulation techniques for diabetic painful neuropathy, post-surgical chronic back and leg pain, spinal cord injury pain, complex regional pain syndrome, primary motor cortex and dorsolateral prefrontal cortex neuropathic pain.
Robust clinical studies are needed in order to demonstrate definitive clinical benefit and on which recommendations for their clinical use can be made for different chronic pain conditions.
- FDA News Release. FDA approves spinal cord stimulation system that treats pain without tingling sensation. Published online May 8, 2015. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm446354.htm. Accessed September 21, 2016.
- Kloimstein H, Likar R, Kern M, et al. Peripheral nerve field stimulation (PNFS) in chronic low back pain: a prospective multicenter study. Neuromodulation. 2014 Feb;17(2):180-187.
- Mitchell B, Verrills P, Vivian D, DuToit N, Barnard A, Sinclair C. Peripheral Nerve Field Stimulation Therapy for Patients With Thoracic Pain: A Prospective Study. Neuromodulation. 2016 Jul 4. [Epub ahead of print]
- Chakrabortty S, Kumar S, Gupta D, Rudraraju S. Intractable sacroiliac joint pain treated with peripheral nerve field stimulation. J Anaesthesiol Clin Pharmacol. 2016;32(3):392-394.
- Cruccu G, Aziz TZ, Garcia-Larrea L, et al. EFNS guidelines on neurostimulation therapy for neuropathic pain. Eur J Neurol. 2007;14(9):952-970.
- Deer TR, Krames E, Mekhail N, et al. The appropriate use of neurostimulation: new and evolving neurostimulation therapies and applicable treatment for chronic pain and selected disease states. Neuromodulation Appropriateness Consensus Committee. Neuromodulation. 2014;17(6):599-615.
- Deer TR, Mekhail N, Petersen E, eta l. The appropriate use of neurostimulation: stimulation of the intracranial and extracranial space and head for chronic pain. Neuromodulation Appropriateness Consensus Committee. Neuromodulation. 2014;17(6):551-570.
- Deer TR, Mekhail N, Provenzano D, et al. The appropriate use of neurostimulation: avoidance and treatment of complications of neurostimulation therapies for the treatment of chronic pain. Neuromodulation Appropriateness Consensus Committee. Neuromodulation. 2014;17(6):571-597.
- Deer TR, Mekhail N, Provenzano D, et al. The appropriate use of neurostimulation of the spinal cord and peripheral nervous system for the treatment of chronic pain and ischemic diseases: the Neuromodulation Appropriateness Consensus Committee. Neuromodulation. 2014 Aug;17(6):515-550.
- Cruccu G, Garcia-Larrea L, Hansson P, et al. EAN guidelines on central neurostimulation therapy in chronic pain conditions. Eur J Neurol. 2016 Oct;23(10):1489-1499.
- International Neuromodualtion Society. Experts Issue Comprehensive Guidance on the Use of Neurostimulation in Chronic Pain. Published online August 1, 2014. Available at: http://newswise.com/articles/experts-issue-comprehensive-guidance-on-the-use-of-neurostimulation-in-chronic-pain. Accessed September 21, 2016.
- Kapural L, Yu C, Doust MW, et al. Novel 10-kHz high-frequency therapy (HF10 therapy) is superior to traditional low-frequency spinal cord stimulation for the treatment of chronic back and leg pain: the SENZA-RCT randomized controlled trial. Anesthesiology 2015; 123: 851–860.
- Forget P, Boyer T, Steyaert A, et al. Clinical evidence for dorsal root ganglion stimulation in the treatment of chronic neuropathic pain. A review. Acta Anaesthesiol Belg 2015; 66: 37–41.
- Onesti E, Gabriele M, Cambieri C, et al. H-coil repetitive transcranial magnetic stimulation for pain relief in patients with diabetic neuropathy. Eur J Pain 2013; 17: 1347–1356.