The burden of chronic pain is enormous in terms of suffering, disability, health care, and social and economic cost. Due the increase in the aging population, chronic pain is foreseen to increase remarkably in Europe in the near future. Currently available medicines for treating neuropathic pain are often unsatisfactory. Medicines for treating inflammatory pain have gastrointestinal (non-steroidal antiinflammatory drugs, NSAIDs), or cardiovascular [cyclooxygenase-2, (COX2) inhibitors, Coxibs)] liabilities, thus increasing morbidity and mortality in the elderly. The opioid epidemic in the US further highlights the inadequacy of current therapies for chronic pain. Thus, it is urgent to understand the fundamental mechanisms of chronic pain and develop more effective therapies. The overall objectives of our project are to understand the mechanisms underlying chronic pain and identify novel targets for better and safer medicines for chronic pain treatment. Acute pain that resolves quickly is a commonly experienced mechanism of survival. Chronic pain, which may persist for years, is associated with inflammatory diseases, peripheral and central neuropathies, cancer, and other diseases, and is a distinct and debilitating condition that affects 25% of European adults. Although activation of pathways in the central nervous system (CNS) contributes to chronic pain, it commonly has its origin from inflammation or tissue damage in the periphery. The hypothesis underlying the project is that, while acute pain is generated by stimulation of receptors and channels expressed in nociceptor nerve terminals, the subsequent chronic mechanical, thermal, and chemical hypersensitivity, the landmark of chronic pain, is sustained via the critical contribution of Schwann cells. Schwann cells (the counterpart of oligodendrocytes of the CNS) are glial cells that wrap, protect, and nourish peripheral nerve fibers. We hypothesized that these glial cells are targeted by a variety of endogenous or exogenous agents to sustain chronic pain with their repertoire of channels, receptors, and enzymes. The specific objectives of our project are to identify the role of Schwann cells in sustaining chronic pain in different mouse models of human diseases (cancer, nerve damage, inflammation, migraine, and others). To this purpose, we have developed innovative tools to selectively delete (or express) genes and related proteins in Schwann cells. This strategy has enabled the identification of novel targets for better and safer analgesic drugs.
