Editors' ChoicePain

Taking a Bite Out of Pain

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Science Translational Medicine  07 Nov 2012:
Vol. 4, Issue 159, pp. 159ec200
DOI: 10.1126/scitranslmed.3005249

The black mamba is one of the world’s deadliest snakes, and a bite is fatal to humans unless antivenom is administered immediately. Now, from this fearsome source comes a potential new treatment for pain. As Diochot et al. report in their new study, black mamba venom contains a new class of three-finger peptides that have an analgesic effect as potent as that of morphine but without the dangerous side effects.

Termed "mambalgins," these tiny proteins (only 57 amino acids long) were found to exert their powerful analgesic effects by blocking acid-sensing ion channels (ASICs), key players in the pain pathway of mammals. In mice, the authors found that mambalgins exerted their analgesic effects by targeting ASIC1a and ASIC2a in the central nervous system neuron and ASIC1b channels expressed by pain receptors (nociceptors) in the peripheral nervous system. When compared with morphine, mambalgins were equally as effective at mitigating acute thermal pain or inflammatory pain but did not elicit tolerance upon repeated administration and did not induce the harmful side effects of morphine, such as slowed breathing.

Pain management is an essential component of clinical practice, but more specific, safe, and potent analgesics are urgently needed to replace morphine. This newly discovered class of proteins from the fangs of the black mamba may substantially advance the treatment of pain not only by offering a new therapeutic option to patients, but also by providing highly specific inhibitors that can be used for studying pain pathways in animal models.

S. Diochot et al., Black mamba venom peptides target acid-sensing ion channels to abolish pain. Nature 490, 552–555 (2012). [Full Text]

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