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A new class of molecules that can relieve pain as effectively as morphinewithout any toxic side effects

A new class of molecules that can relieve pain as effectively as morphinewithout any toxic side effects

In a recent article entitled, “Black mamba venom peptides target acid-sensing ion channels to abolish pain” published online in Nature  on October 3, 2012(Nature 490,552–555, doi:10.1038/nature11494) Sylvie Diochot and her associates  report of   isolating  a new class of peptide from the extremely poisonous African black mamba snake that can bring relief to pain through the inhibition of particular subtypes of acid-sensing channel (ASIC) expressed either in central or peripheral neurons.

Mamba venom is one of the deadliest and fast-acting venom of any land snake.  Sylvie Diochot and Anne Baron at CNRS  (Centre national de la recherche scientifique), France have discovered a new class of molecules among the cocktail of chemicals in the black mamba’s venom. The new class of molecules  can relieve pain as effectively as morphine but without any toxic side effects. They have named these compounds mambalgins. Their effect differs from the analgesia associated with previously identified animal peptides in their capacity to  block ASICs that activate  the enkephalin system. Diochot and Baron started  their investigation by searching animal venom for chemicals that could block ASICs – a group of pain-inducing proteins called acid-sensing ion channels. They are like miniature gates, which dot the surface of neurons.

Following an injury, our damaged cells release an “inflammatory soup” of chemicals that trigger feelings of pain. Among the first of these harbingers are simple protons – positively charged particles that make the local tissues more acidic.  ASICs detect and respond to protons by opening up, allowing positive ions to flood inside thereby causing the neurons to fire. They serve as warning systems that communicate to our bodies that something is wrong. Diochot and Baron found two peptides (short proteins) from black mamba venom that block ASICs—mambalgin-1 and mambalgin-2. They act as padlocks that latch onto the closed proteins and stop them from opening, even when surrounded by protons. They work quickly and effectively against every type of ASIC found in our nervous system. As painkillers, they numb the sharp pain of a burn, as well as the dull throb of an inflamed limb. They are incredibly specific: they don’t stop neurons from firing normally , and they don’t block any of the other gate-keeping proteins found in these cells. Unlike other similarly shaped proteins, they don’t have any toxic effects, i.e. they do not cause  paralysis, convulsions or breathing difficulties. Baron says, “Cobra venom, and more recently the corresponding purified cobrotoxin, have been used for instance for the control of pain in traditional Chinese medicine”. But cobrotoxin can also paralyze muscles; mambalgins, on the other hand, kill pain. These findings identify new potential therapeutic targets for pain relief and introduce natural peptides that block them to produce a potent analgesia. [summarized by Ms Sumaiya Farah Khan, Jannath University]

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