Growth hormone releasing hormone reverses endotoxin-induced localized inflammatory hyperalgesia without reducing the upregulated cytokines, nerve growth factor and gelatinase activity.
During inflammatory processes, the hypothalamic-pituitary axis is activated which can subsequently result in analgesia. For example, hypothalamic corticotrophin-releasing hormone (CRH) that is released during such activation has been attributed with analgesic actions. It is believed that the somatotrophic axis is also activated during inflammation. The aim of this study was to determine the analgesic actions of growth hormone-releasing hormone (GHRH), in a rat model of localized inflammatory hyperalgesia, induced by intraplantar (i.pl.) endotoxin (ET) injections. Pretreatment with intraperitoneal (i.p.) injections of GHRH (2, 5, 10 microg kg(-1)) 30 min before i.pl. ET injection (1.25 microg in 50 microl saline) prevented, in a dose-dependent manner, both mechanical hyperalgesia determined by the paw pressure (PP) test and thermal hyperalgesia determined by the hot plate (HP) and paw immersion (PI) tests. Pretreatment with GHRH had no significant effect on the elevated levels of the inflammatory mediators, interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, IL-6 and nerve growth factor (NGF) due to i.pl. ET injection. No significant effect was obtained by pretreatment with GHRH, on the increased expression of gelatinase B due to ET injection. In conclusion, GHRH reverses inflammatory hyperalgesia in the rat without affecting the upregulated inflammatory mediators and these actions may be clinically important.
Talhouk
Rabih S
RS
Department of Biology, Faculty of Arts and Sciences, American University of Beirut, P.O. Box 11-0236, Riad El-Solh, 1107-2020, Lebanon. rtalhouk@aub.edu.lb
Saadé
Nayef E
NE
Mouneimne
Ghassan
G
Masaad
Cynthia A
CA
Safieh-Garabedian
Bared
B
D000700:Analgesics; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001522:Behavior, Animal / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism*; D004487:Edema / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D004731:Endotoxins / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000633:toxicity; D005528:Foot / Q000473:pathology; D018093:Gelatinases / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D006930:Hyperalgesia / Q000139:chemically induced / Q000517:prevention & control*; D007274:Injections, Intraperitoneal; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000378:metabolism*; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation / Q000187:drug effects*
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D004731:Endotoxins; D007375:Interleukin-1; D015850:Interleukin-6; D009414:Nerve Growth Factors; D014409:Tumor Necrosis Factor-alpha; D013007:Growth Hormone-Releasing Hormone; D018093:Gelatinases