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A new target for painkillers

North Carolina co-authors tied sutures loosely around one of each rat's two sciatic nerves to mimic nerve compression and injury from sciatica. That made the rats overly sensitive to touch on one hind paw but not the other. Each rat's sensitivity was assessed by measuring how much pressure could be applied to a hind paw with a blunt Teflon tip before the rat pulled away the paw.

Normal rats could withstand 4.7 times more pressure before withdrawing their paws, compared with rats with sciatica. When cone snail toxin RgIA was injected, the rats with sciatica were able to tolerate a stronger touch from the tip ?both four hours and 24 hours after the drug was given. The highest dose completely reversed the hypersensitivity caused by sciatica, with no adverse effects. Daily injections "produced a sustained analgesic effect," the researchers wrote.

RgIA was such a potent pain reliever that "about 10 billionths of an ounce reversed the hypersensitivity to pain," McIntosh says.

Vc1.1 had a similar effect ?replicating studies by other researchers ?allowing rats with sciatica to tolerate touch with greater pressure.

The new study is not McIntosh's first involving chronic pain. As an incoming college freshman working in Olivera's lab in 1979, McIntosh discovered in cone snails the natural form of a drug now used against severe nerve pain. It is Prialt, which must be injected into fluid surrounding the spinal cord as a treatment for severe pain due to cancer, AIDS, injury, failed back surgery and certain nervous system disorders.
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Source:University of Utah


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