Editorial [Hot Topic: Ion Channels as Therapeutic Targets for Neuropathic Pain (Executive Editor: Char-Chang Shieh)]

Management of neuropathic pain remains as medical challenge although numerous drugs such as opiates, anticonvulsants (gabapentin), antidepressants, and recent approved Prialt, a N-type Ca2+ channel blocker, have been prescribed to alleviate chronic pain. Their uses are limited by addiction, the inadequacy in pain relief and adverse side effects. Over the last decade, significant scientific progress has been made to reveal the mechanisms underlying neuropathic pain. The emerging novel pronociceptive mediators and mechanisms that are involved in the development and maintenance of chronic pain have transformed into therapeutic approaches, which inspire significant investment from pharmaceutical industry to identify novel efficacious analgesic agents. Ion channels are class of membrane proteins that play important roles in cellular excitability and pain signaling pathway. Preclinical research has identified an array of ion channels involved in the generation and transduction of pain as potential targets for pharmacological intervention. In this issue of Current Pharmaceutical Design, the leading scientists review the advancement of researches on the efforts to discover novel therapeutic agents by modulating ion channels. Boyce-Rustay and Jarvis [1] review the distinct neurophysiological and neurochemical mechanisms that contribute to pain arising from injury to the nervous system. The preclinical rodent pain models that have been reliably used to study nociceptive changes in neuropathic pain and to assess the analgesic effects of drugs are described. Burnstock [2] provides a comprehensive review on purinergic signaling, receptor subtypes of purines and pyrimidines and their mechanosensory transduction involved in visceral, cutaneous and musculoskeletal nociception as well as in neuropathic and inflammatory pain. Current developments of compounds for the treatment of both visceral and neuropathic pain in “pe-clinical animal pain models” are discussed. Cortright and Szallasi [3] review roles of a family of thermosensitive transient receptor potential channels, referred to as “thermoTRPs”, in the transduction of a wide range of noxious stimuli. The vanilloid (capsaicin) receptor TRPV1 represents the first channel in this family to be identified as a pain target by genetic deletion and pharmacological inhibition experiments. Other members of this family including TRPA1 (transient receptor potential, ankyrin subfamily member 1) and TRPM8 (transient receptor potential, melastatin subfamily member 8) were demonstrated to be involved in pain signaling pathway including mechanical hypersensitivity and cold allodynia. The TRP channels represent a new strategy in pain relief aiming to prevent pain by blocking a receptor where pain is generated. Cortright and Szallasi review significant advancement from the cloning of TRPV1 to clinical trials with potent small molecule TRPV1 antagonists within last decade. The emerging evidence that supports particular TRP channels as targets for novel analgesic drugs, along with potential adverse effects that may limit drug development is discussed.