Identifying Novel Molecular Targets for Treating Chronic Pain.

Chronic pain is a global problem that affects one in five Australians, with even higher prevalence in the elderly. Most pain drugs are designed to target nociceptive pain (eg: a burn or a sprained ankle) and patients with this form of pain respond well to pharmacological treatment. Neuropathic pain, on the other hand, is caused by malfunction of the nervous system and does not respond well to current pain therapies. There is an enormous unmet need for drugs to treat neuropathic pain. The first step in developing effective therapeutics, is the identification of cellular targets that control signalling in the damaged pain pathways.
We have recently identified a novel circuit that is susceptible to damage in neuropathic pain (Imlach et al., 2016). Manipulating activity in the circuit may be an effective strategy to treat pathological pain. In order to understand how changes in this circuit affect activity and novel pharmacological targets that may control signalling, we propose the following aims: 1) use patch clamp electrophysiology to investigate intrinsic activity and modulatory mechanisms of inhibitory neurotransmission, 2) identify a specific pattern of molecular markers in neurons within the circuit that will allow us to genetically target this population, 3) Identify molecular signalling components that are specifically altered in the radial cells circuitry after peripheral nerve injury and assess their causal contribution to abnormal processing in this pathway by manipulating them pharmacologically, by knock-down or overexpression.
The next generation of pain therapeutics is dependent on the discovery of new targets that can control excitability in the neural circuits that generate pathological pain. The benefits from this research – in terms of enhanced individual wellbeing, reduced healthcare costs, and advancing knowledge – are substantial.