Black Mamba Venom: As Painless as Morphine

A team of scientists recently reported the discovery of a new class of pain-relieving compounds, isolated from the venom of the black mamba (Dendroaspis polylepis). When injected into the spines of mice, the compounds, peptides known as mambalgins, were found to produce a painkilling effect as strong as that of morphine—one of the most powerful pain-relieving drugs known to medicine.

A black mamba (Dendroaspis polylepis). Credit: © Heiko Kiera/Fotolia

Morphine, described chemically as an opium alkaloid, works by mimicking the actions of endorphins, substances that occur naturally in the body and that suppress pain by binding to a specific type of receptor (the mu receptor) found on neurons in the central nervous system. Morphine binds to the same receptors. Mambalgins, however, exert their effects through a completely different mechanism. They block tiny channels in the membranes of neurons that are sensitive to acid, a substance that induces pain in humans.

Morphine is used mainly as a last resort for relief from severe pain, typically the kind of pain experienced by patients with terminal cancer, because it is addictive and toxic. These effects are associated with the mu receptor, which in response to morphine binding generates not only pain-relief and euphoria (the effect sought after by recreational opium users) but also respiratory depression and physical dependence. Over the long-term, the body develops tolerance to morphine, such that increasing doses of the drug are needed to effect pain relief. The new mambalgins appear to have few side effects, at least in mice, which would make them especially valuable as clinical agents.

While snake venom has been emphasized lately as a potentially rich source of compounds for drug development, the discovery of the painkilling mambalgins came as a surprise. The black mamba’s venom is extremely potent, and why the venom acts on acid-sensing channels is unclear, though it probably has little to do with soothing the victim’s pain once it has been bitten. Rather, it likely has to do with evolution and phenomena such as overcoming venom resistance in prey.

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