Pain experts discuss new frontiers in neuromodulation

The International Neuromodulation Society (INS) recently held their 4th Scientific Meeting entitled Neuromodulation: New Frontiers. The INS is a non-profit group comprising clinicians, scientists and engineers whose aim is the scientific development and awareness of neuromodulation.

The theme of the New Frontiers meeting is the increasing neurotechnology industry, which is offering new treatments for many disorders whose ailments have previously not been relieved by conventional treatments.

The meeting was chaired by Dr Rick Acland and included a distinguished panel of speakers including Professor Micheal Cousins AM; Timothy Deer MD, DABPM, FAADEP, CIME; Peter Georgius FFPMANZCA, FAFRM; Professor Nicolai Bogduk MD, PhD, DSc, FFPMANZCA; James O’Callaghan FANZCA, FFPMANZCA; and Charles Brooker MBChB, MRCP(UK), FFPMANCA.

First on the program was a presentation by Professor Cousins on ‘Neuropathic pain: current concepts in relation to neuromodulation’. While animal models have allowed a lot of progress into the understanding of neuropathic pain, results of drug treatments in animal models have not been shown to reliably predict outcomes in patients. Maladaptive changes can occur at many levels within the nervous system and may include phenotypic changes, altered gene expression and neuroplasticity changes. Recent evidence has also suggested a role for a small family of genes that determine the likelihood of progression from an acute phase to persistent neuropathic pain.

Neuroplasticity changes in humans have now been associated with amputation pain, neuropathic pain in spinal cord injury, motor disturbances and complex regional pain syndrome. Interestingly there is a correlation between the severity of pain in spinal cord injury and brain neuroplasticity changes.

Neuromodulation has evolved into an important pharmacologic and non-pharmacologic option in the management of neuropathic pain. New non-opioid drugs targeting spinal neuroplasticity changes are set to create resurgence in the use of spinal drug administration while neurostimulation as a method of non-pharmacological neuromodulation continues to evolve.

The topic of ‘Advances in Neuromodulation’ was discussed by Dr Deer. With 75,000 neurostimulators implanted worldwide each year, the field of neurostimulation is growing dramatically. Indications for implantation of neurostimulators include pain treatment, certain neurological diseases including Parkinson’s disease and visceral syndromes including gastric dysmotility. Dr Deer’s discussion focused on the current uses of neurostimulation in failed back surgery syndrome, complex regional pain syndromes, ischaemic pain, angina, peripheral neuropathy and neuropathic foot pain.

Dr Deer discussed technological advances impacting patient care including lead technology, generator technology, computer technology platforms, patient selection and physician education. He also discussed areas that have the potential to change the future of the field but as yet have not made a clinical impact. These include:

MRI compatible systems;
Wireless technology;
Self contained systems;
Percutaneous paddle lead technology;
Multi-electrode computer arrays; and
Peripheral nerve implants.

The discussion included a review of recently researched drugs including octreatide, a growth hormone analog shown to have some efficacy in neuropathic pain; and gabapentin, a GABA analogue currently being studied in open label and randomised blinded prospective studies. Several conotoxins, neurotoxic peptides derived from the venom of the marine cone snail, where discussed. This included the use of ziconotide (Prialt) as a current therapy, approved for intrathecal use by the FDA in the treatment of chronic intractable pain. Ziconotide is non-addictive and as an analgesic is 1000 times more potent than morphine. Future intrathecal conotoxins include Xen2174, CGX-1160 and AM336.

Dr Georgius presented ‘Non-nociceptive effects of intrathecal agents’. While intrathecal agents have a significant role in pain management, the non-nociceptive effects of these drugs are complex and can involve multiple systems. The homeostasis of endocrine, autonomic and immune systems can be altered leading to significant effects on pain modulation. Non-nociceptive effects may also alter the stress response including changes to the sympathetic nervous system, the pro-inflammatory cytokines and lymphocytes as well as the hypothalamic-pituitary-adrenal axis.

A major hurdle in assessing the effectiveness of an intervention is whether or not the response reported by a given patient is attributable to the active component of the intervention. Professor Bogduk explained the use of ‘N of 1 trials & application to neuromodulation’ in answering this question. In N of 1 trials, there is one patient who is allocated randomly to receive either active or sham versions of the intervention under either double blind or single blind conditions. If the response of the patient is attributable to the intervention, the patient will consistently respond to treatment with the active intervention but not to the sham intervention.

To overcome chance variations, multiple iterations are required. The number of iterations is dependant on the magnitude of the response and the differences in magnitudes of responses to active or sham treatment. Larger differences in response are more are statistically significant and so require less iteration.

Persistent or recurrent pain, reduced functionality and reduced quality of life despite anatomically successful lumbosacral surgery is seen in patients with failed back surgery syndrome. It has been shown in selected patients that pain reduction, improved quality of life, reduced use of analgesics, improved sleep and functionality including return to work can be achieved with spinal cord stimulation. Dr O’Callaghan presented the results to PROCESS; a study of 100 patients randomised to either conventional medical management (CMM) of failed back surgery or CMM plus spinal cord stimulation. The study concluded that spinal cord stimulation can result in sustained pain relief (24 months), improved functionality, health related quality of life and patient satisfaction.

Dr Brooker summarised the use of implanted intrathecal drug pumps and the current evidence for the use of different drugs in patients with spinal cord injury and multiple sclerosis. In Dr Brooker’s presentation on ‘intrathecal drug delivery for spinal cord injury: current status and future direction’, he also discussed technical issues relating to the use of implantable pumps in these patients.

To conclude the presentations Dr Deer presented ‘Peripheral nerve stimulation (PNS) and peripheral nerve field stimulation (PNFS)’. These techniques are based around the principle that the nerve implicated in pain generation can be easily stimulated in the periphery and this stimulation can effect the transmission of pain signals via A delta and C fibres.

PNS involves identification of the nerve involved in pain transmission and the direct application of an electrical current. Careful dissection and a fascial graft are required, which can be technically challenging and fraught with problems. Hence for most clinical disease states PNFS has superseded the use of PNS.

PNFS is performed under local anaesthetic following mapping of the nerve field. The needle is then placed in the subcutaneous tissue with care to avoid placement either too superficially causing lead erosion, or too deeply in which case the nerve fibres may be missed.

Both techniques have application in occipital neuralgia, neuritis of the face, upper extremity pain and pain of the torso, pelvis or lower extremities. Complications of both techniques include cellulitis and peripheral nerve injury as well as mechanical dysfunction of the leads and/or generator. The presentation focused on patient selection, lead placement and clinical pearls in order to achieve optimal clinical outcomes.

References

International Neuromodulation Society. Neuromodulation: New Frontiers. 4^th Scientific Meeting, The Australian Chapter, International Neuromodulation Society.