title: Endogenous opioids released during non-nociceptive environmental stress induce latent pain sensitization Via a NMDA-dependent process.
abstract: Although stress induces analgesia, there is evidence that stressful events may exacerbate pain syndromes. Here, we studied the effects of 1 to 3 prestressful events (days 0, 2, and 7), such as non-nociceptive environmental stress, on inflammatory hyperalgesia induced by a carrageenan injection (day 14) in 1 rat hind paw. Changes in nociceptive threshold were evaluated by the paw pressure vocalization test. The higher the number of stress sessions presented to the rats, the greater was the inflammatory hyperalgesia. Blockade of opioid receptors by naltrexone before each stress inhibited stress-induced analgesia and suppressed the exaggerated inflammatory hyperalgesia. Stressed versus nonstressed animals could be discriminated by their response to a fentanyl ultra-low dose (fULD), that produced hyperalgesia or analgesia, respectively. This pharmacological test permitted the prediction of the pain vulnerability level of prestressed rats because fULD analgesic or hyperalgesic indices were positively correlated with inflammatory hyperalgesic indices (r(2) = .84). In prestressed rats, fULD-induced hyperalgesia and the exaggerated inflammatory hyperalgesia were prevented NMDA receptor antagonists. This study provides some preclinical evidence that pain intensity is not only the result of nociceptive input level but is also dependent on the individual history, especially prior life stress events associated with endogenous opioid release.
  
  
  CONCLUSIONS
  Based on these preclinical data, it would be of clinical interest to evaluate whether prior stressful events may also affect further pain sensation in humans. Moreover, this preclinical model could be a good tool for evaluating new therapeutic strategies for relieving pain hypersensitivity.
authors: Université Bordeaux, INCIA, CNRS UMR 5287, F-33076 Bordeaux, France.
authors: Chloé
authors: C
authors: Le Roy
authors: Emilie
authors: E
authors: Laboureyras
authors: Stéphanie
authors: S
authors: Gavello-Baudy
authors: Jérémy
authors: J
authors: Chateauraynaud
authors: Jean-Paul
authors: JP
authors: Laulin
authors: Guy
authors: G
authors: Simonnet
mesh_terms: D000701:Analgesics, Opioid; D000704:Analysis of Variance; D000818:Animals; D002351:Carrageenan / Q000633:toxicity; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005283:Fentanyl; D006930:Hyperalgesia / Q000209:etiology*; D007249:Inflammation / Q000139:chemically induced / Q000150:complications; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D009271:Naltrexone; D009292:Narcotic Antagonists; D018847:Opioid Peptides / Q000378:metabolism*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013315:Stress, Psychological / Q000150:complications*; D013550:Swimming / Q000523:psychology; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D018691:Excitatory Amino Acid Antagonists; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D016194:Receptors, N-Methyl-D-Aspartate; D009271:Naltrexone; D007649:Ketamine; D002351:Carrageenan; D005283:Fentanyl