Researchers have discovered that certain components in the venom of the black mamba snake are able to relieve pain
The sense of pain is one of the most complex things in our body. It responds to several qualitatively different stimuli. For example, high heat causes pain, as does the substance found in hot pepper, mechanical pressure, strong stretching, and more. The painful stimulus is absorbed by exposed nerve endings throughout the body, which have special proteins that function as receptors or as different ion channels, which are sensitive to the pain signals. The nerve endings receive the stimulus and create an electrical response that is transmitted to the spinal cord and from there to the brain, which interprets the response as pain. Some of these nerve endings have ion channels that are particularly sensitive to acid, and their activation causes a sharp, burning pain.
For many years, toxic substances from various sources have been used to study and understand the properties of ion channels. For example, the pogo fish tetrodotoxin has been used as a powerful tool to understand how the sodium ion channel works in nerve cells. This toxin blocks the canal and therefore causes nerve paralysis. That fish, by the way, is a well-known Japanese delicacy, and only chefs who have specialized in removing its poisonous parts are allowed to serve it. Snake venoms also affect the nervous system, and many are known to activate acid-sensitive ion channels, which is why they cause pain. A group of researchers from France used the venom of the black mamba snake to study acid-sensitive ion channels. The mamba snake is the longest venomous snake in Africa, and the fastest in the world. Because of its speed, aggression and high toxicity, it is considered by many experts to be the deadliest snake known to us. The venom of the mamba snake is extremely painful and contains many toxins, but the researchers focused, as mentioned, only on the components that affect ion channels, and here comes the big surprise. They discovered that molecules isolated from the venom of the black mamba snake, not only did not cause pain, but on the contrary, they acted as pain relievers, by blocking the activity of acid-sensitive ion channels. This group of substances was called in their mouths by the name of membalgins.
The researchers showed that membalgins inhibit the activity of acid-sensitive ion channels in both mice and humans, and even conducted behavioral experiments in mice. In these experiments they found that the pain threshold increased considerably after the injection of membalgin. Hambalgin worked both when injected directly into the brain and in peripheral tissues. The pain relief effectiveness was similar to that of morphine, but without the negative side effects of morphine. Not only that, but membalgins did not have other negative side effects known from other toxins, such as impairments in motor activity. Morphine is a pain reliever from the opiate group, to which opium also belongs, and despite being a powerful pain reliever, continuous use of this substance often causes the development of dependence or alternatively the development of resistance. Also, morphine has potentially life-threatening side effects, such as respiratory depression. For this reason, the great importance of this work is that a new group of substances with the ability to treat pain was found, whose effect is similar in strength to that of morphine, but without the dangerous effects. Another important finding is the degree of involvement of acid-sensitive ion channels in mediating pain. These channels will undoubtedly serve as a target not only for membalgins but also for future drugs to treat pain, drugs that may be even more effective than membalgins themselves.
Credit: Daphne Axel
About the author
Itzhak Frances He was a professor in the neurobiology department of the Hebrew University of Jerusalem, he founded the Israeli Society for Neuroscience and established the Belmonte Youth Laboratories in Jerusalem. Professor Ferns passed away shortly after this column was written.
And more on the subject
Black mamba venom peptides target acid-sensing ion channels to abolish pain. Diochot et al. in Nature Vol. 490, pages 552-557, October 2012
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