TRP channels as therapeutic targets: hot property, or time to cool down?

ABSTRACT

Transient receptor potential (TRP) channels are involved in a wide range of processes ranging from osmoregulation, thermal, chemical and sensory signalling, and potentially in the pathophysiology associated with several diseases. Patents for TRPV1 antagonists alone span diseases ranging across chronic pain, neuropathies, headache, bladder disorders, irritable bowel syndrome (IBS), gastro-oesophageal reflux disease (GORD), and cough amongst others. Most research is currently focused around those TRP channels involved in sensory processes, with the neurogastroenterology and motility field playing a major role, for example, through recent discoveries of differential roles for TRPV receptor subtypes in chemosensitivity and mechanosensitivity of visceral afferents. At this time, however, the understanding of the role of even TRPV1, let alone most of the other TRP channels in disease pathophysiology is only just beginning, and although enthusiasm around the therapeutic potential for modulators of these channels is understandable, based largely upon the experience of the effects of natural ligands, such as capsaicin, the sheer size and complexity of the TRP family as a whole must serve as a warning against expecting too much too soon from drug discovery efforts.