Melatonin reversal of lipopolysacharides-induced thermal and behavioral hyperalgesia in mice.
The perception of pain sensation (threshold), whether local or central, is altered by inflammatory processes. Anti-inflammatory drugs block this by raising the pain threshold and by reducing the inflammatory process. Melatonin is claimed to have anti-inflammatory activity in animal models of acute and chronic inflammation. However, it is not known whether melatonin can reverse the hyperalgesia that is secondary to the inflammation. The present study aimed to assess the modulatory effect of melatonin on lipopolysaccharides-induced alteration of pain perception in mice. Central perception of pain was assessed with the tail-flick and hot-plate methods and local hyperalgesia was assessed by noting the animal's reactions such as paw licking and rearing after the intraplantar injection of lipopolysaccharides (5 microg/paw). Local administration (intraplantar) of lipopolysacharides induced hyperalgesia when measured by both central effects and behavioral reactions. Melatonin (5 and 10 mg/kg), like dexamethasone (0.5 mg/kg), given 30 min prior to, and 4 and 8 h after lipopolysaccharides (5 microg/paw) challenge attenuated central and behavioural hyperalgesia. The attenuation of lipopolysaccharides-induced hyperalgesia by melatonin was not reversed by naltrexone (4 mg/kg). In vitro studies showed that melatonin, in concentrations ranging from 100 to 1000 nM, suppressed tumor necrosis factor-alpha (TNF-alpha) without affecting the nitric oxide (NO) release in lipopolysaccharides-activated murine peritoneal macrophages. Taken together, the present results demonstrated that melatonin reverses lipopolysaccharides-induced hyperalgesia.
Raghavendra
V
V
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Agrewala
J N
JN
Kulkarni
S K
SK
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D008070:Lipopolysaccharides / Q000008:administration & dosage* / Q000009:adverse effects; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009271:Naltrexone / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D009271:Naltrexone; D003907:Dexamethasone; D008550:Melatonin