Press release

TOWARDS A NEW CLASS OF PAIN RELIEF?
A success of the post-genomic approach

Researchers from the Pasteur Institute have characterized the activity of a molecule, sialorphin, in rats and demonstrated that it is a powerful modulator of pain perception. As a result, sialorphin could be the leader of a new class of natural molecules intended for pain relief. This research was published in PNAS.

Sialorphin is a molecule secreted in rats in some stressful situations: the researchers characterized its mechanism of action and discovered that it was a powerful analgesic.

This discovery is a significant consequence of the post-genomic approach, since the researchers of the Pasteur Institute - especially François Rougeon, Director of the Developmental Genetic and Biochemistry Unit - had identified the sialorphin gene before its function was known. The research, involving teams from the CEA in Saclay, the ETAP-Applied Ethology Research Centre and the H. Poincaré University in Nancy as well as the Pasteur Institute, was coordinated by Catherine Rougeot, Director of the Research and Development Laboratory of Pharmacology of Neuro-endocrine Regulations.

Sialorphin intervenes in the regulation of the activity of enkephalins, the physiological opiate peptides involved in controlling pain perception. Enkephalins are inactivated by an enzyme, NEP. The Pasteur researchers demonstrated that sialorphin was a natural inhibitor of NEP, and that it thus prevented the inactivation of enkephalins in the nervous tissues.

Through behavioural tests, the researchers demonstrated that sialorphin exerts its analgesic potency by activating certain pathways of the endogenous opioid system. The opioid receptors are essential in transmitting endogenous antinociceptive signals, such as enkephalins, as well as in transmitting exogenous opiates, such as morphine. Sialorphin's antinociceptive effect is abolished by antagonists blocking the opioid receptors. Thus, sialorphin inhibits the sensation of pain by potentiating the opioidergic system.

Sialorphin, a powerful inhibitor of pain perception, could hence give rise to new natural substances to fight against pain.

Sources:

- "Sialorphin, a natural inhibitor of rat membrane-bound neutral endopeptidase that displays analgesic activity". PNAS, July 8 2003, 100 (14): 8549-54
Catherine Rougeot1, Michaël Messaoudi2, Véronique Hermitte1, Anne Gaëlle Rigault1, Thierry Blisnick3, Christophe Dugave4, Didier Desor5, and François Rougeon1

1 Unité de Génétique et biochimie du Développement (Developmental Genetic and Biochemistry Unit), Institut Pasteur, Paris (France)
2 ETAP- Ethologie Appliquée (ETAP-Applied Ethology), Vandoeuvre-lès-Nancy (France)
3 Unité de Biologie des Interactions Hôte-Parasite (Biology of Host-Parasite Interactions Unit), CNRS URA 1960, Institut Pasteur, Paris (France)
4 Département d'Ingénierie et d'Etudes des Protéines Protein Engineering and Research Department), CEA/Saclay, Gif-sur-Yvette (France)
5 Laboratoire de Biologie et Physiologie du Comportement (Behavioural Biology and Physiology Laboratory), Faculty of Sciences, Université Henri Poincaré, Vandoeuvre-lès-Nancy (France)

Contacts :

- Catherine Rougeot - Pharmacologie des Régulations Neuroendocrines (Pharmacology of Neuro-endocrine Regulations)
Tel.: 01 40 61 34 45 - Email: crougeot@pasteur.fr

- Press Office, Institut Pasteur, Paris
Tél : 01 45 68 81 46 ; e-mail : presse@pasteur.fr