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Health News Archive 503 - Pain
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Probiotic Exhibits Intestinal Pain Reduction Similar to Morphine

Oral administration of the probiotic Lactobacillous acidophilus NCFM has been seen to have an analgesic effect in the gut similar to that of morphine.

Marketed under the name Howaru Dophilus, the strain is one of Danisco Cultures' flagship strains and has been extensively tested for its gut health benefits, stability and survivability through the gastrointestinal tract.
The findings of the study, conducted at French research institute Inserm and the University of Lille and a brief communication of which is published in Nature Medicine have been patented by Danisco. The company is already in discussions with potential partners in the pharmaceutical, dietary supplement and food industries over its use in commercial products.

The researchers hypothesised that probiotics may induce the expression of receptors on epithelial cells that control transmission of nociceptive information to the intestinal nervous system. In particular, opioid receptors and cannabinoid receptor 2 were judged to be promising.

The first step of the study involved evaluating five Lactobacillus and Bifidobacterium bacteria for the induction of expression of analgesic receptors in human HT-29 epithelial cells. The NCFM strain was seen to induce a sustained increase of OPRM1 mRNA expression, and to induce significant cannabinoid receptor expression (CNR2 mRNA) compared to that observed in resting epithelial cells.

The researchers went on to conduct in vivo experiments with mice and rats. NCFM was orally administered at a dose of 109 for 15 consecutive days. In the treated animals' colonic section expression of MORI and CB2 was detected in 25-60 per cent of epithelial cells, compared to 0-20 per cent in the untreated animals.

To determine the visceral perception of rats, the researchers used colorectal distension, whereby pain is characterized by visible abdominal contractions and elevation of the hindpart of the animal's body. The NCFM strain was seen to decrease normal visceral perception and increase the pain threshold by 20 percent – an affect that increased as the dosage increased.

In a model of chronic colonic hypersensitivity, the probiotic was seen to increase colorectal distension threshold by 44 percent compared to untreated rates, and had an antinococeptive effect like that of 1 mg of subcutaneous morphine per kg of body weight.

Lead researcher Professor Pierre Desreumaux, head of the department of gastrointestinal diseases and nutrition at Lille University and research director at Inserm said: “One could envision NCFM to be prescribed for intestinal function disorders or co-administered with morphine to relieve serious gastrointestinal pathologies, therefore reducing morphine doses and related side effects.”

Danisco is currently conducting additional, complementary studies in the US on people suffering from irritable bowel syndrome (IBS).

A spokesperson for the company called the development “an interesting new function for probiotics”. She said that there is a large target market for the application area – abdominal or intestinal pain is thought to affect between 10 and 20 per cent of adults in the world, according to the World Health Organization. In particular, it is one of a collection of symptoms associated with IBS. 

“On probiotics in general we always search for new functionalities to enable development of new areas of application,” said the spokesperson, adding that the research was conducted specifically with a view to improving treatment of pain for people with severe gastrointestinal diseases.  The Howaru Dophilus strain is said to be the world's only commercially-available Lactobacillous acidophilus with a fully sequenced annoted genome.

Source: Christel Rousseaux, Xavier Thuru, Agathe Gelot, Nicolas Barnich, Christel Neut, Laurent Dubuquoy, Caroline Dubuquoy, Emilie Merour, Karen Geboes, Mathias Chamaillard, Arthur Ouwehand, Greg Leyer, Didier Carcano, Jean-Frédéric Colombel, Denis Ardid and Pierre Desreumaux. Lactobacillus acidophilus modulates intestinal pain and induces opioid and cannabinoid receptors. Nature Medicine; Published on-line ahead of print, doi: 10.1038/nm1521.

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