A Brief History of Neuromodulation
Electricity, mainly from electric fish, was used for thousands of years to treat pain and other conditions. After it became possible to store and to control electricity in the mid eighteenth century its popularity increased enormously, both as quackery and for serious applications such as numbing the pain during dental operations. The modern era of neuromodulation began in the early 1960s, first with deep brain stimulation which was soon followed (in 1967) by spinal cord stimulation, both for otherwise intractable pain. The gradual realisation that pain was the result of complex dynamic processes in the nervous system and not simply the result of activity in a hard-wired system was greatly enhanced by the publication of the Gate Theory in 1965. As damage to the nervous system can itself cause chronic pain, there began a gradual move away from destructive surgical treatments such as cutting nerves and towards reversible, modulatory treatments: neuromodulation.
The applications of therapeutic electrical stimulation are very diverse and new applications are being developed. The treatment of refractory chronic pain is the commonest indication, particularly neuropathic pain but also ischaemic pain. Spinal cord stimulation is the commonest modality and its use in treatment of neuropathic pain of peripheral origin and in ischaemic pain such as Angina and Critical limb ischaemia is well established.
As deep brain stimulation for pain declined in the 1980s it began to be used to treat movement disorders such as Parkinson’s disease and this application is growing rapidly.
Peripheral nerve stimulation for pain relief in neuropathic pain is also receiving increasing attention. Intractable epilepsy has been treated variously with deep brain stimulation, cerebellar cortex stimulation and vagal nerve stimulation. Vagal nerve stimulation also appears to have a mood elevating effect and is starting to be used to treat depression and obsessive compulsive disorder.
The use of deep brain stimulation to treat severe intractable depression and obsessive compulsive disorder is being actively explored with promising initial results.
Motor cortex stimulation by means of brain surface electrodes was introduced in 1991 and is used to treat the pain suffered by some stroke victims and by people with damage to the trigeminal nerve. These are conditions for which very little else is available. Overcoming incontinence, both urinary and faecal, by means of electrical nerve stimulation is not new, but in recent years the techniques have improved and this application is receiving a great deal of attention, and is likely to become more available. Chronic visceral pain is much commoner than chronic somatic pain and it appears that this will probably be the next big new application of neuromodulation.
The implantable devices used for neuromodulation have steadily improved over the last four decades and recently have taken a leap forward with the introduction of rechargeable systems, smaller devices, and systems with greater but useable complexity. As the hardware becomes smaller and more user friendly for both doctor and patient, it seems likely that the use of neuromodulation will grow. Tens of thousands of units are already implanted annually but this represents only a small proportion of those people who could benefit.
The idea that opiate drugs such as morphine might be more effective if injected directly into the spinal fluid (i.e intrathecally) was first tested in 1977 and the first internalised infusion pump was implanted in 1981. Such pumps have developed from patient-activated bolus devices and constant infusion systems to complex programmable units. Intrathecal morphine was first used for cancer pain but is now widely used for severe pain of non cancer origin in patients with normal life expectancy.
Several other drugs are also suitable for this approach and are often used in combination. Much smaller doses are required because the drug does not have to escape metabolism and cross the blood brain barrier before reaching its site of action. There are fewer side effects but the wide individual variation in both responsiveness and side effects can mean that this treatment is unsuitable for some patients. Many tens of thousands of patients do benefit from this treatment, particularly those with mechanical pain, a mixture of pain types, pain multiple areas and cancer pain.
Baclofen has been the most widely used drug in treating spasticity since its introduction in 1971. However, when taken orally it crosses the blood brain barrier very poorly so that high blood levels of the drug are required to achieve satisfactory levels in the cerebrospinal fluid and nervous system. This often results in unpleasant side effects and lack of efficacy. The direct intrathecal administration of baclofen was first reported in 1984 and, dose for dose, achieves a concentration in the cerebrospinal fluid approximately 400 times higher. Intrathecal baclofen has proved to be extremely effective in controlling spasticity due to spinal cord injury and diseases such as multiple sclerosis and can also be effective in spasticity of cerebral origin (brain injury, stroke, hypoxia). In addition to its often dramatic effect against spasticity, intrathecal baclofen was found to have an analgesic effect; reports have appeared since the early 1990s regarding its effectiveness in some cases of neuropathic pain and its use in augmenting spinal cord stimulation.
Ziconotide is a new agent to treat severe pain. It can only be given intrathecally from precision infusion devices and needs to be managed carefully. This novel agent relieves pain in a different way to currently used intrathecal drugs and may form a useful tool in the pain physician’s armamentarium.
Like stimulation devices, intrathecal drug delivery pumps are becoming smaller (or the same overall size can have a bigger reservoir) and more user friendly. The bigger the reservoir the longer the interval between refills but the stability of the drug in solution over time has to be taken into account. Also like neurostimulation, intrathecal drug delivery systems are being implanted in steadily increasing numbers.
Neuromodulation is an invasive treatment but for selected patients whose chronic conditions cause suffering and disability it can bring considerable relief and improvement, often after all other measures have failed. It is to be hoped that the availability of this clinical and cost effective treatment will continue to increase. Its earlier implementation may even modify the course of some conditions; it should not be regarded as a treatment of last resort.
The application of functional electrical stimulation (FES) had its origins in the management of spinal injury and post stroke care. A number of external and implantable devices have been designed and manufactured to restore useful function in an otherwise intact nervous system. Applications and outcome aims range from a method of enhancing physical rehabilitation after such an injury to the restoration of upper and lower limb function, bladder function and chest ventilation after complete spinal cord injury.
Simon Thomson, MBBS FRCA FIPP
President, International Neuromodulation Society, 2009 - 2015
Basildon & Thurrock University Hospital, U.K.
Sept. 16, 2010
(Please note: This information should not be used as a substitute for medical treatment and advice. Always consult a medical professional about any health-related questions or concerns.)