Chronic, neuropathic pain remains a massive source of disability which contributes to loss to work forces and tremendous suffering worldwide. It can be caused by a range of conditions such as cancer, stroke and trauma. Drugs are limited in their analgesic effects and are not without sedative side effects. They can also be expensive for an increasingly refractory group of patients, writes Tipu Aziz and Erlick Pereira
Intractable neuropathic pain syndromes were among the earliest indications for deep brain stimulation over six decades ago before it became established for Parkinson’s disease in the last quarter of a century. In search of optimal alleviation, numerous brain targets were explored including the septal area, sensory thalamus, periventricular/periaqueductal grey regions (PAG) and internal capsule. In the early studies, short-term efficacy was demonstrated but fully implantable systems had not yet been developed. The brain electrodes were home made by scientific and surgical pioneers and needed externalisation to extracorporeal stimulation devices.
From early clinical experiences and relevant animal studies (in which stimulation of PAG saw diminished responses to experimental pain in rats and cats) deep brain stimulation for pain continued to evolve in clinical case series by dedicated neurosurgeons. Important scientific experiments assessing whether PAG and thalamic analgesic mechanisms were opioid mediated were complemented by findings from deep brain stimulation, with some suggestion that its effects were blocked by naloxone. In the early 1970s fully implantable devices became commercially available and deep brain stimulation for intractable pain became widespread with further case series demonstrating sustained benefit in significant proportions of patients.
In the 1980s, Medtronic sponsored two multicentre efficacy trials, both of which were considered failures because neither achieved greater than 50% pain relief in more than 50% of enrolled patients available to follow-up. The trials suffered from both lack of recruitment and loss of patients to follow-up. Many centres had recruited less than a handful of patients each, which made surgeons’ experience with the technique questionable. US Food and Drug Administration (FDA) approval was therefore not attained and the procedure was thus largely abandoned. However, reviewing patients’ responses to deep brain stimulation for pain in those that remained amenable to follow-up in the latter trial using more contemporary electrodes, revealed a significant success rate that could have resulted in device approval had so many patients not been lost from the studies.
Outside the USA, deep brain stimulation for chronic pain was pursued in a few centres, notably in Germany, the UK, and recently Portugal with promising results. Oxford has just published a 12-year series of 74 implanted patients with varied neuropathic pain with 66% of patients demonstrating a maintained benefit at four-year follow-up. Aetiologies which showed the most improvements included amputation, brachial plexus injury, stroke and head and facial pain of various causes. This large series uses the latest generation of implantable devices from both Medtronic and St Jude Medical.
Therefore, it appears that deep brain stimulation for intractable pain is an efficacious therapy but should be offered to carefully selected patients in specialist centres experienced in pain management and willing to study their outcomes rigorously to contribute to an increasing body of knowledge about this procedure.
Tipu Aziz is a consultant neurosurgeon and Erlick Pereira is a neurosurgery registrar, both with the Oxford University Hospitals, Oxford, UK
