Neuromodulation for Chronic Pain

20th October 2015
By Danielle Santarelli, PhD

Neuromodulation represents an advanced pain management therapy for patients with chronic pain that is unresponsive to conservative treatment. In terms of clinical application, neuromodulation refers to the therapeutic administration of electrical stimulation or chemical agents directly to the nervous system (spinal cord, brain or peripheral nerves) in order to “modulate” nerve cell activity. The goal for the chronic pain patient is to interrupt or mask pain signalling, though the precise mechanisms of the therapy are not fully understood.

The first sophisticated application of neuromodulation dates back to the early 1960’s, when deep brain stimulation (DBS) was first used to treat chronic, intractable pain. DBS involves the surgical implantation of electrodes within the brain which are wired to a pacemaker type device that is implanted under the skin on the chest. The device delivers electrical impulses to the target brain areas in order to mask abnormal activity. In the present day, DBS is primarily used in the treatment of neurological movement disorders, such as Parkinson’s disease, essential tremor and dystonia.

The application of spinal cord stimulation (SCS) commenced shortly after DBS, in 1967, and it is now the most established neurostimulation modality for the treatment of chronic pain, with a well-documented efficacy and safety profile. SCS involves the implantation of leads into the epidural space that are connected to an implanted pulse generator, which is generally placed under the skin on the lower backside. The position of the stimulating leads along the spinal cord depends on the area of pain. Before permanent implantation of the device, patients undergo a trial. Trial leads are implanted and connected to an external device, usually for 7 – 14 days. The trial is successful if the patient experiences a ≥50% decrease in pain. SCS can also improve functionality and allow a patient to reduce their analgesic medication intake.

Common indications for SCS are failed back surgery syndrome and complex regional pain syndrome (CRPS). The effectiveness of SCS is most well demonstrated in chronic low back and leg pain. Improved effectiveness for these conditions and a wider range of pain distributions has been achieved with recent advances in SCS technology, namely high frequency SCS and burst stimulation SCS, though traditional low frequency SCS systems remain effective for many patients, particularly those with predominant leg pain. Another variation of SCS is dorsal root ganglion stimulation (DRGS). Dorsal root ganglia are aggregations of nerve cell bodies that sit adjacent to the nerve roots exiting the spine and regulate the entry of sensory information to the spinal cord. The aim of targeting the DRG is to stop pain signals from entering the spinal cord.

Nerves outside of the spinal cord can also be stimulated in order to treat chronic pain conditions; this is known as peripheral nerve stimulation (PNS). PNS is also used to treat conditions such as paraplegia and epilepsy. The target nerve is directly stimulated by implanting and anchoring an electrode on, near or around the nerve. In peripheral nerve field stimulation (PNFS), electrodes are placed subcutaneously in the site of most pain to stimulate the surrounding nerves.

Neuromodulation also refers to the delivery of chemical agents to the nervous system. Intrathecal pumps are implantable drug delivery systems. Drugs are delivered directly to the cerebrospinal fluid, therefore bypassing oral drug route metabolism and barriers. This means that drug dose can be significantly lowered and side effects are minimised.

References & Further Reading:

  1. Cameron T. Safety and efficacy of spinal cord stimulation for the treatment of chronic pain: a 20-year literature review. Journal of neurosurgery 2004; 100:254-267.
  2. Compton AK, Shah B, Hayek SM. Spinal cord stimulation: a review. Current pain and headache reports 2012; 16:35-42.
  3. Dafny, N. Pain Modulation and Mechanisms.
  4. International Neuromodulation Society. About Neuromodulation. 2010;
  5. Kunnumpurath S, Srinivasagopalan R, Vadivelu N. Spinal cord stimulation: principles of past, present and future practice: a review. J Clin Monit Comput 2009; 23:333-339.
  6. McMahon S, Bennet D. Pain Mechanisms [Poster]. Nature Reviews Neuroscience. 2007;
  7. Schaible HG. Peripheral and Central Mechanisms of Pain Generation. Handb Exp Pharmacol. 2007; 177:3-28.
  8. Slavin KV. Peripheral nerve stimulation for neuropathic pain. Neurotherapeutics. 2008; 5:100-106.
  9. Stucky, CL, Gold MS, Zhang, X. Mechanisms of Pain. PNAS. 2001;
  10. Van Buyten JP. Neurostimulation for chronic neuropathic back pain in failed back surgery syndrome. Journal of pain and symptom management 2006; 31:S25-29.
  11. Image by Mconnell. distributed under a CC BY 3.0 license. File:Anterior_thoracic_SCS.jpg

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