Lick your wounds

To ‘lick one’s wounds’ is not just a figure of speech. It is actually beneficial to do so; human saliva contains antimicrobial com- pounds, and the saliva of rodents is known to contain nerve growth factor. Now, we can add pain killers to the list of useful substances found in saliva: a team of neuroendocrinologists at the Pasteur Institute in Paris have found that human saliva contains an analgesic neuropeptide. The peptide, which has been named opiorphin, is six times more potent than morphine, and its mechanism of action could lead to the development of new pain killers.

The analgesic effects of opiorphin are produced by its actions on the opioid system, which consists of three families of endogenous opioids (the enkephalins, endorphins and dynorphins) and the opioid receptors to which they bind. The opioid peptides are short peptides which are synthesized in the brain, and released at nerve terminals in the spinal cord in response to pain. By binding to opioid receptors on sensory neurons, they block the transmission of pain signals to the brain, but their actions are short-lived because, like all neurochemical transmitters, they are quickly broken down by enzymes. In the absence of pain, the endogenous opioids produce feelings of euphoria. The structure of synthetic opioids such as morphine and heroine resembles those of the endogenous opioids, and these drugs mimic the actions of endogenous opioids by binding to opioid receptors (endorphin is an abbreviation of endogenous morphine).

Reporting in the Proceedings of the National Academy of Sciences, Catherine Rougeot and her colleagues show that the analgesic effect of opiorphin is produced by the inhibition of two called ectopeptidases (human neutral ecto-endopeptidase, hNEP and human ecto-aminopeptidase, hAP-N), which normally break down enkephalins. By inhibiting these enzymes, opiorphin prolongs the actions of enkephalins at synapses in the spinal cord.

Rougeot’s team carried out a series of behavioural tests to determine the effect of opiorphin on chemically- and mechanically- induced pain in rats. Administration of opiorphin led to decreased paw-licking in rats which had been injected with a pain-inducing chemical and also to reduced pain in the ‘pin-pain’ test, in which the animals are placed on a surface overlaid with vertical stainless steel pins. Both of these tests provide strong evidence that opiorphin had significant anti-nociceptive effects.

Opiorphin is closely related to sialorphin, another analgesic discovered by the same group three years ago. Sialorphin is synthesized predominantly in the submandibular and prostate glands of adult rats, is released in response to stress, and acts by inhibiting the enzymatic degradation of enkephalin and substance P, another neuropeptide released by sensory neuron terminals in response to painful stimuli.

The enzymes inhibited by opiorphin could prove to be useful targets for new analgesic drugs. Because opiorphin is such a simple molecule, researchers could synthesize it easily instead of having to purify it from human sailvary glands. A problem with developing opiorphin-based drugs, however, is the lack of specificity of the peptide: because it inhibits two enzymes, synthetic ectopeptidase inhibitors could produce unwanted side effects.


3 thoughts on “Lick your wounds

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  3. “Usog” is a concept in psycho-medicine in Filipino Psychology where an affliction or psychological disorder is attributed to a greeting by a stranger. It usually affects an unsuspecting child, usually an infant, who has been greeted by a visitor. Once affected, the child begins to develop fever, and sometimes convulsions. Supposedly, to counter the effects of “usog” the visitor is asked to put some of his or her saliva on the baby’s tummy or forehead before leaving the house, then leaves while saying: “Pwera usog… pwera usog…” The stranger is never to lick the child; the saliva is placed on the finger first, before the finger is rubbed on the baby’s tummy or forehead (“lalawayan”) to prevent the child from getting overpowered.

    The practice to counteract “usog” using saliva is very Filipino. I suggest therefore, for those interested in research, to determine whether the saliva of Filipinos contain more opiorphin than other races. Perhaps, Filipinos have salivary composition adaptations, as Sherpas were found to have more hemoglobin in their blood than other people, in their adaptation to thinner oxygen in the Himalayas.

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