Beyond the lamppost: approaches to answering the questions of interest.

摘要

As goes the story of the man found on his hands and knees looking for his lost keys under the light of the lamppost, scientists are often accused of using one model system or another, not necessarily because it is the most appropriate to answer the question of interest, but because it is the easiest to use. This may be particularly true for the study of pain in which, for example, hypersensitivity to punctate mechanical stimuli is widely used as a measure of "neuropathic pain" in preclinical models of peripheral neuropathy because it is so robustly manifest in rodents despite the fact this form of hypersensitivity is not a primary, or even secondary, positive sign of neuropathic pain in patients. So, given that pain associated with tissue damage, the most common source of pain, is generally due to neural activity initiated in the peripheral terminals of nociceptive afferents, it is reasonable to ask why one would want to study the cell body of the primary afferent to learn anything about the mechanisms underlying this neural activity. Gemes et al. described a novel approach to study the cell body of primary afferents in the intact ganglia. Importantly, however, they have not developed this approach to learn anything about afferent terminals. Rather, they have described a powerful way to study signaling at the afferent cell body.