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There are 6 pages to this Feature:
Molecular Approaches to Neuroscience
- The Main Course - A Satisfied
Customer - Q&A - BTC - Photos & References
A Satisfied Customer
Allan Basbaum was a student at the first offering of Molecular Approaches to
Neuroscience in the summer of 1995. Allan enrolled in the course, as he puts it,
"to find out whether it [was] a direction that I wanted to take." Upon
completion of the molecular techniques training, Allan returned to his laboratory at the
University of California-San Francisco and began implementing the techniques in his
neuroscience studies. A few years (and experiments) later, Allan and his colleagues
produced a PPT-A knockout mouse and in 1998 reported the
findings on the involvement of PPT-A and substance P in pain reception in Nature.
"It's not that I learned how to make the mice, but that I had a much better
understanding of the language of the techniques so that I could better interact with the
people in the lab who were doing the work."--A. Basbaum, UCSF
Briefly, substance P was suspected in the signaling of pain, but
its precise contribution and how it interacted with other putative "pain"
transmitters, notably glutamate, was unclear. Substance P is encoded by the gene, preprotachykinin
A (PPT-A), as is the related tachykinin, neurokinin A. In their knockout mouse,
pain in the moderate to intense range was abated significantly, as was the neurogenic
inflammation associated with the peripheral release of substance P and neurokinin A. Their
conclusion: the release of tachykinins from primary afferent pain-sensing receptors, or
nociceptors, is required for pain emission in the moderate to intense range.
[Click on figure to view higher resolution image]
'Pain' responses to different thermal or mechanical stimulus
intensities. Panel a, Licking/jump latency in the hot-plate
assay (n=12); at 55.5°C the homozygous mutant mice (black bars) showed a decreased pain
response compared to wildtype (white bars). Panel b, Paw withdrawal
latencies to noxious thermal stimuli (n=8): at midrange intensities (8.0 volts), mutant
mice also showed a decreased pain response. Panel c, Withdrawal threshold
to a mechanical stimulus (von Frey hair; n=16); wildtype and mutant mice do not differ. Panel
d, Response latency to tail clip (wildtype: n=31; homozygous mutant: n=21); the
pain response of the mutant mice is significantly delayed (**, P < 0.01)
(1).
Figure reprinted from Nature (1998)
392, 390, by permission of Macmillan Magazines, Ltd., and Dr. A. Basbaum.
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