Polyamine deficient diet to relieve pain hypersensitivity.
There is a compelling body of evidence that N-methyl-d-aspartate receptors (NMDA-R) play a critical role in the development and maintenance of pain hypersensitivity. However, long-term treatments with NMDA-R antagonists are limited by unacceptable side effects. Since polyamines modulate the functioning of NMDA-R and mainly originate from normal dietary intake and bacterial metabolism in the gut, we developed a nutritional therapy based on dietary polyamine deficiency. Here, we reported that a polyamine deficient diet (PD diet) for 7 days prevented the enhancement of tyrosine phosphorylation of the spinal NR2B subunit-containing NMDA-R associated with inflammation in rats. Based on these data, we studied the ability of PD diet to prevent long-lasting pain hypersensitivity associated with tissue injury on one hind paw by evaluating long-lasting changes in both mechanical nociceptive threshold and weight bearing. A PD diet strongly reduced long-lasting hyperalgesia induced by inflammation or incision, especially in fentanyl-treated rats. Moreover a PD diet also prevented the exaggerated hyperalgesia induced by a second inflammation performed 7 days after the first one. A PD diet also opposed paradoxical hyperalgesia induced by non-nociceptive environmental stress in rats with pain and opioid experiences. A PD diet reversed pain hypersensitivity associated with monoarthritis or neuropathy and restored the analgesic effect of morphine. Since PD diet was devoid of any noticeable side effects, this nutritional therapy could be part of an effective and safe strategy for pre-emptive analgesia and for reducing the transition from acute to chronic pain and its outcomes in various pain syndromes.
Rivat
Cyril
C
Université Bordeaux 2, Université Bordeaux 1, UMR CNRS 5227, "Mouvement-Adaptation-Cognition", Team "Homéostasie-Allostasie-Pathologie-Réhabilitation", 146 Rue Léo Saignat, 33076 Bordeaux Cedex, France Department of Anesthesia and Intensive Care II, Hôpital cardiologique Haut Lévèque, Service du Professeur Gérard Janvier, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France Groupe de Recherche en Thérapeutique Anticancéreuse, EA 3891, Université de Rennes 1, 2 avenue du Pr. Léon Bernard CS 34317, 35043 Rennes, France UMR CNRS 7157, Neuropsychopharmacologie des Addictions, Université René Descartes Paris 5, 4 avenue de l'Observatoire, 75270 Paris Cedex 06, France.
Richebé
Philippe
P
Laboureyras
Emilie
E
Laulin
Jean-Paul
JP
Havouis
René
R
Noble
Florence
F
Moulinoux
Jacques-Philippe
JP
Simonnet
Guy
G
D000818:Animals; D004035:Diet Therapy / Q000379:methods*; D006930:Hyperalgesia / Q000178:diet therapy* / Q000378:metabolism; D008297:Male; D010147:Pain Measurement / Q000379:methods; D011073:Polyamines / Q000008:administration & dosage*; D011700:Putrescine / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley
D011073:Polyamines; D011700:Putrescine