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IT MAY be possible to get morphine鈥檚 painkilling effects without having to
take ever larger doses鈥攁nd, possibly, without risking withdrawal symptoms.
The finding turns conventional theories on their head.

Morphine kills pain by mimicking the body鈥檚 natural opiates, binding to
special ised receptors on nerve cells. When natural opiates bind to them, the
receptors are sucked inside the cell鈥攁 process called
endocytosis鈥攁nd then return to the cell surface. But when morphine binds
to the receptors, it blocks endocytosis.

This was thought to prolong morphine鈥檚 effect and give it its power. 鈥淚t
seemed like the last thing you鈥檇 want to do to is trigger endocytosis,鈥� says
Jennifer Whistler of the University of California, San Francisco.

Whistler鈥檚 team set out to test this theory when they discovered that a
protein called DAMGO could trigger endocytosis of morphine-bound receptors. They
used a standard pain test in which a laser is focused on the tail of rats. The
rats normally flick their tails away in about two seconds.

Rats given morphine didn鈥檛 flick their tails for six seconds. But the effects
soon wore off. After four days on the same dose, the animals flinched after just
two seconds.

But when the researchers added a tiny trace of DAMGO to the morphine, the
results were dramatic. Even after a week, the animals鈥� response hardly changed
at all. By itself, though, DAMGO had no effect.

DAMGO can鈥檛 be used to treat people鈥攊t is too large to enter the
brain鈥攂ut Whistler thinks drugs witht the same effect could be found. The
findings also have implications for related opiates such as heroin. Could
junkies get more bang for their buck with such a booster, for example?

Glen Hanson of the US National Institute on Drug Abuse isn鈥檛 sure.
Painkilling is different to the high such drugs create, he says. And whether
endocytosis affects withdrawal and addiction isn鈥檛 yet clear. 鈥淭his raises a lot
of exciting issues,鈥� he says. 鈥淭here are going to be a ton of phenomena to
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