Both neuropathic pain and epilepsy are common chronic disorders which result in significant morbidity to the sufferer, and have a major impact on health resources. Severe chronic pain costs the Australian economy $34 billion per year, and may carry a global health impact equivalent to that of heart disease or severe mental illness. Chronic pain suffers attend to primary care physicians five times more frequently than those without pain. There is a critical need for better understanding and management of chronic pain. Epilepsy affects 1- 3% of the adult population, and morbidity associated with epilepsy is associated with injury related to seizure, loss of license, the cost of life-long need for medication, and the side effects associated with anticonvulsants. While vastly different in their clinical manifestations, abnormal nerve excitability is implicated in the pathogenesis of both neuropathic pain and epilepsy. Therefore, we aim to study these conditions in tandem to evaluate the mechanism by which abnormal nerve excitability results in symptoms.
Nerve cell membranes are electrically active. Ion channels are membrane-bound proteins which allow the passage of charged particles (ions) across the membrane of nerve cells. Dysfunction of ion channels (genetic or acquired) can result in abnormal nerve excitability. Neurological features caused by ion channel dysfunction include seizures, ataxia, migraine, pain, epilepsy and stroke-like symptoms. Assessment of ion channel dysfunction previously relied on in vitro expression of single channels. This cannot factor in the complex cascade of interactions that occur in vivo, therefore a tool to sensitively measure ion channel function in vivo is critically needed in order to define pathophysiology, aid diagnosis, monitor progress and assess treatment outcomes. The TROND protocol of nerve excitability studies is a non-invasive test performed in a similar fashion to nerve conduction studies. It provides information regarding channel function in peripheral nerve. While the central nervous system cannot be directly interrogated, peripheral nerves carry many similarities and can provide a surrogate marker of channel function in the CNS.
This project seeks to define how specific channel currents (including Ih, due to HCN channel activity) result in aberrant nerve excitability and pacemaker misfire, and play an important role in generation of neuropathic pain AND seizures. The project has 2 arms with similar study design. One arm will study patients with neuropathic pain and the other arm will study patients with seizures/epilepsy. Subjects will undergo clinical assessment and nerve excitability studies annually for 3-5 years. It is anticipated that peripheral nerve excitability studies will be contribute to defining the mechanism of disease, and potentially predict outcome and response to treatment. Hence, the role of nerve excitability studies as an aid to diagnosis and management in these cohorts will be explored and defined.