Pathophysiology of neuropathic pain: Signaling pathways and their magnification–the role of neuronal toll-like receptors

Introduction: Neuropathic pain is a tremendous challenge to the healthcare system. It is thought that 7-8% of the population in the USA is affected by chronic pain and in 5% it may be severe. The personal and economic impacts of chronic pain are significant, as approximately half of sufferers are unable to work full-time and/or participate fully in the activities of daily life. Although there are a number of current treatments available for inflammatory pain, pharmaceuticals for chronic neuropathic pain are quite often inadequate. Furthermore, many of these compounds (opioids, non-steroidal anti-inflammatory drugs (NSAIDs) and non-NSAIDs such as ziconotide) are not ideal as they suffer from tolerability and/or safety issues. It is clear that there is a need for new approaches to this problem is clear. Work described in this chapter investigates the potential role in neuropathic pain of a class of neuronal receptors formerly thought to only reside on immune and glial cells. Investigations into neuropathic pain mechanisms often utilize the rationale that the onset of spontaneous activity in neurons following peripheral nerve injury may trigger abnormal pain behavior in rodents (perhaps better defined in animals as hyperalgesia) and neuropathic pain in humans [1]. It may then follow that the neuropathic pain state is dependent on chronic alterations in the physiology (spontaneous and/or ectopic discharge) of both nociceptive and non-nociceptive sensory neurons [2-4]. Many potential mediators and pathways have been examined as potential contributors to chronic neuropathic pain. In this chapter, we will study an important mediator and its associated factors, the Toll-like receptor.