Peripheral regulation of nociception by antidepressants, purines and noradrenaline

The local delivery of drugs to the site of origin of certain pains (as a cream, gel, or patch) has the potential to have the clinical advantage of producing lower drug levels throughout the body and fewer adverse drug effects compared to oral drug treatments. Over the past few years, there have been significant advances made in understanding the molecular mechanisms and tissue mediators involved in initiating pain at peripheral sites in sensory nerves. The main aims of the present proposal are to further understand the peripheral influences of antidepressants and purines (ATP, adenosine) on peripheral pain signaling in the uninjured state and following different forms of nerve injury. This information will be of direct relevance to the development of novel topical analgesics for the relief of various types of pain. This includes neuropathic pain which can result from trauma (e.g. accident, surgery), metabolic factors (e.g. diabetes), toxic factors (chemotherapy-induced neuropathy) or infections (e.g. post-herpetic neuralgia).