Neuromodulation, or Neuromodulatory Effect

The International Neuromodulation Society defines therapeutic neuromodulation as “the alteration of nerve activity through targeted delivery of a stimulus, such as electrical stimulation or chemical agents, to specific neurological sites in the body.” (1) In appropriate patients, this growing class of therapies, in common use since the 1980s, can help restore function or relieve symptoms that have a neurological basis.

How Neuromodulation Therapy Exerts Its Effects

Neuromodulation devices stimulate nerves – with pharmaceutical agents, electrical signals, or other forms of energy – by modulating abnormal neural pathway behaviour caused by the disease process. Profound effects occur including relief of pain, restoration of function or normal bowel and bladder control, Parkinson’s and tremor control and many more. (2)

The reversible therapy delivers stimulation to specific neural circuits in the brain, spine, or peripheral nerves. Depending on the target, the therapy may be non-invasive or minimally invasive.

Whether the devices are implanted or external, neuromodulation therapies can help reestablish neural balance, similar to the way a cardiac pacemaker or defibrillator corrects heartbeat abnormalities.

Neuromodulation Treatments

Neuromodulation approaches range from non-invasive techniques such as transcranial magnetic stimulation to implanted devices, such as a spinal cord stimulation or a deep brain stimulation system.

The most common neuromodulation treatment is spinal cord stimulation for chronic neuropathic pain. (3-10). In addition to chronic pain relief, other neuromodulation treatments now used or studied include deep brain stimulation for essential tremor, Parkinson’s disease, dystonia, epilepsy and disorders such as depression, obsessive compulsive disorder and Tourette syndrome; sacral nerve stimulation for pelvic disorders and incontinence; gastric and colonic stimulation for gastrointestinal disorders such as dysmotility or obesity; vagus nerve stimulation for epilepsy, obesity or depression; carotid artery stimulation for hypertension; and spinal cord stimulation for ischemic disease such as angina and peripheral vascular disease. (2, 10-22)

When Neuromodulation is Considered

Neuromodulation therapy may be considered for select patients, through a multidisciplinary assessment, either as an adjunct to other care, or when symptoms do not adequately respond to more conservative measures, for instance, when existing drugs are ineffective or become problematic for long-term use due to development of tolerance, addiction, adverse side-effects or toxicity.

Implanted Neuromodulation Devices

Neuromodulation therapy continues to undergo refinement and research elucidating its effects and applications. Electrical neurostimulation implants are believed to activate natural biological responses, such as nerve transmission and release of the body’s own pain-reducing substances, in the neural circuits receiving stimulation.

Central to the operation of electrical-stimulation implants are thin insulated leads, placed beneath the skin, that are tipped by electrical contacts. The contacts, no bigger than a grain of rice, are positioned beside the nerve or nerves that influence the condition being treated. Pulses of mild electrical current are sent down the leads to the nerves.

A battery-operated generator that is about the size of a stopwatch powers the pulses. If a patient responds well to several days of trial treatment, this sort of pulse generator will be implanted too. After the system has been implanted, a clinician will work with the patient to program the stimulation pattern, which can be adjusted over time. At home, patients use hand-held controllers to turn off or switch between programs. Recuperation from the implant procedure may take a few weeks.

In the case of pharmacological agents delivered through implanted pumps – such as pain relief medication or anti-spasm agents – medication can be given in smaller doses because it does not have to be absorbed through the intestines, like a drug taken by mouth, and then pass through the liver before circulating to the target area. Smaller doses – in the range of 1/300th of an oral dose – can mean fewer side effects, increased patient comfort, and improved quality of life. Patients return periodically to have the drug reservoir refilled. (23)

Patients will be briefed to watch for potential complications, such as signs of infection or a mechanical issue, and their caregivers should be sure to consult the implant provider if any questions arise with this or other treatments over the years. Patients with an implant should not pass through security gates, and will be given a card to show security personnel.  

The Role of Neuromodulation in Managing Chronic Conditions

While they are not a cure for an underlying condition, neuromodulation therapies provide an additional means of managing symptoms of chronic conditions. Despite their technological complexity, neuromodulation devices, when introduced relatively early in treatment, may be more cost-effective at controlling certain conditions over time than medical management approaches. Examples include spinal cord stimulation for the treatment of neuropathic pain and intrathecal baclofen for the treatment of severe spasticity. (2-4, 7, 10, 23)

Current and Potential Future Development of Neuromodulation

Overall, neuromodulation therapies have become an integral tool for healthcare professionals since first becoming available in the 1960s. As with most medical technologies, neuromodulation devices have progressed, becoming smaller, more easily implanted and removed, and more highly targeted. Those advances, combined with an increasing body of knowledge and practitioner skill, can all contribute to cost-effective use of the therapy in chronic conditions.

A continued growth in scientific understanding of neural circuitry, along with advances in biomedical engineering, are likely to contribute to an ongoing evolution in neuromodulation treatment options and progress in the utility of this treatment for patients and practitioners.

The development of neuromodulation therapies has been truly multidisciplinary, requiring close collaboration between neuroscientists, engineers and clinicians to aid many patients who face vexing and long-term conditions.

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Conventional medicine has typically had four modes of treating diseases or disorders . . .

Selected References:

  1. International Neuromodulation Society. Welcome to the International Neuromodulation Society. Accessed Dec. 21, 2016

  2. Mekhail NA, Cheng J, Narouze S, Kapural L, Mekhail MN, Deer T. Clinical applications of neurostimulation: forty years later. Pain Pract. 2010;10(2):103-112.

  3. North RB et al. Spinal cord stimulation versus re-operation in patients with failed back surgery syndrome: an international multicenter randomised controlled trial (EVIDENCE Study). Neuromodulation 2011;14:330–6.

  4. Wilkinson HA. Spinal cord stimulation versus reoperation for failed back surgery syndrome: A cost effectiveness and cost utility analysis based on a randomized, controlled trial. Neurosurgery. 2008;63(2):E376.

  5. Kumar K et al. The effects of spinal cord stimulation in neuropathic pain are sustained: a 24-month follow-up of the prospective randomised controlled multicenter trial of the effectiveness of spinal cord stimulation. Neurosurgery 2008;63(4):762–770.

  6. Thomson S, Jacques L. Demographic characteristics of patients with severe neuropathic pain secondary to failed back surgery syndrome (PROCESS study). Pain Practice 2009;9:206-214.

  7. Taylor RS, Van Buyten JP, Buchser E. Spinal cord stimulation for complex regional pain syndrome: a systematic review of the clinical and cost effectiveness literature and assessment of prognostic factors.  Eur J Pain.  2006;10(2):91-101.

  8. Cameron T. Safety and efficacy of spinal cord stimulation for the treatment of chronic pain: A 20-year literature review. J Neurosurg Spine 100(3):254-267, 2004.

  9. Krames E et al. Using the SAFE principles when evaluating electrical stimulation therapies for the pain of failed back surgery syndrome. Neuromodulation 2011;14:299–311.

  10. Simpson, EL, Duenas, A, Holmes, MW, Papaioannou, D, Chilcott, J. Spinal cord stimulation for chronic pain of neuropathic or ischaemic origin: systematic review and economic evaluation. Health Technol Assess. 2009 Mar;13(17):iii, ix-x, 1-154.

  11. Ekre O et al. Long-term effects of spinal cord stimulation and coronary artery bypass grafting on quality of life and survival in the ESBY study. Eur Heart J 2002;23:1938–1945.

  12. Amann W, Berg P, Gersbach PA et al. Spinal cord stimulation in the treatment of non-reconstructable stable critical leg ischaemia: results of the European peripheral vascular disease outcome study (SCS-EPOS). Eur J Vasc Endovasc Surg 2003; 26:280-286.

  13. Spincemaille GH, de Vet HC, Ubbink DT et al. The results of spinal cord stimulation in critical limb ischaemia: a review. Eur J Vasc Endovasc Surg 2001; 21:99-105.

  14. Blok, B.F., et al., Different brain effects during chronic and acute sacral neuromodulation in urge incontinent patients with implanted neurostimulators. BJU Int, 2006. 98(6): p. 1238-43.

  15. Hassouna, M.M., et al., Sacral neuromodulation in the treatment of urgency-frequency symptoms: a multicenter study on efficacy and safety. J Urol, 2000. 163(6): p. 1849-54.

  16. Levy R, Deer TR, Henderson J. Intracranial neurostimulation for pain control: a review. Pain Physician. 2010;13(2):157-165.

  17. Weaver FM, Follett K, Stern M, et al. Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial. JAMA. 2009;301(1):63-73.

  18. Zesiewicz TA, Sullivan KL, Arnulf I, Chaudhuri KR, Morgan JC, Gronseth GS, et al. Practice Parameter: treatment of nonmotor symptoms of Parkinson disease: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology . 2010 Mar 16;74(11):924-31.

  19. Sharan AD, Rezai AR. Neurostimulation for Epilepsy. In: Krames ES, Peckham HP, Rezai AR, eds. Neuromodulation. London: Elsevier; 2009:617–66.

  20. Deer, T. R., Lamer, T. J., Pope, J. E., Falowski, S. M., Provenzano, D. A., Slavin, K., Golovac, S., Arle, J., Rosenow, J. M., Williams, K., McRoberts, P., Narouze, S., Eldabe, S., Lad, S. P., De Andrés, J. A., Buchser, E., Rigoard, P., Levy, R. M., Simpson, B. and Mekhail, N. (2017), The Neurostimulation Appropriateness Consensus Committee (NACC) Safety Guidelines for the Reduction of Severe Neurological Injury. Neuromodulation: Technology at the Neural Interface. doi:10.1111/ner.12564

  21. Deer, T. R., Provenzano, D. A., Hanes, M., Pope, J. E., Thomson, S. D., Russo, M. A., McJunkin, T., Saulino, M., Raso, L. J., Lad, S. P., Narouze, S., Falowski, S. M., Levy, R. M., Baranidharan, G., Golovac, S., Demesmin, D., Witt, W. O., Simpson, B., Krames, E. and Mekhail, N. (2017), The Neurostimulation Appropriateness Consensus Committee (NACC) Recommendations for Infection Prevention and Management. Neuromodulation: Technology at the Neural Interface. doi:10.1111/ner.12565

  22. Deer, T. R., Narouze, S., Provenzano, D. A., Pope, J. E., Falowski, S. M., Russo, M. A., Benzon, H., Slavin, K., Pilitsis, J. G., Alo, K., Carlson, J. D., McRoberts, P., Lad, S. P., Arle, J., Levy, R. M., Simpson, B. and Mekhail, N. (2017), The Neurostimulation Appropriateness Consensus Committee (NACC): Recommendations on Bleeding and Coagulation Management in Neurostimulation Devices. Neuromodulation: Technology at the Neural Interface. doi:10.1111/ner.12542

  23. Krames, E., Poree, L. R., Deer, T. and Levy, R. (2009), Rethinking Algorithms of Pain Care: The Use of the S.A.F.E. Principles. Pain Medicine, 10: 1–5.

Reviewed Jan. 24, 2013
President, International Neuromodulation Society, 2009-2015
Consultant in Anaesthesia and Pain Management, Basildon and Thurrock University NHS Trust, U.K.
Last Updated on Sunday, November 21, 2021 08:16 PM