A “LETTER BOMB” molecule that destroys renegade nerve cells in rats could
provide relief for people suffering from chronic pain.
Chronic pain occurs when nerve cells in the spinal cord amplify pain
responses by mistake, making a pinprick feel like a knife stab. Cancer,
arthritic swelling or nerve damage can all trigger the condition. Powerful
analgesics such as morphine ease the suffering but can have serious side
Pain-amplifying neurons use a neurotransmitter called substance P to
communicate with each other. So Patrick Mantyh of the University of Minnesota in
Minneapolis and his colleagues decided to transform this innocuous messenger to
carry a deadly payload into the renegade neurons.
To make the new chemical, dubbed SP-SAP, they linked substance P to saporin,
a toxic plant protein. Mistaking the molecule for the genuine neurotransmitter,
the cells take it in and are then poisoned.
To test the effectiveness of the treatment, Mantyh’s team damaged the spinal
nerves of rats, then measured the weight that an animal could tolerate on a paw
before it withdrew it in pain. Animals that had been given a spinal infusion of
SP-SAP could tolerate more than twice the weight compared with controls given
placebos. The pain relief was still active 200 days after the treatment. The
rats remained sensitive to mildly painful stimuli, for which morphine was still
an effective analgesic, showing that other mechanisms for pain sensing and
control were unaffected.
“It is important, imaginative work,” says Stephen Hunt, a molecular
neuroscientist at University College London. “It’s as if they’ve taken away
pain’s volume control.”
Mantyh says that since the drug destroys neurons, it might only ever be
appropriate for extreme cases, such as relieving the pain of people who are
terminally ill. But he thinks it should also be possible to make the “letter
bomb” carry a less destructive payload. “We can try to slow down the neurons, or
maybe even change their behaviour,” he says.
Science (vol 286, p 1558)