PMID- 25871298 OWN - NLM STAT- MEDLINE DCOM- 20160815 LR - 20151106 IS - 1423-0216 (Electronic) IS - 1021-7401 (Linking) VI - 22 IP - 6 DP - 2015 TI - Short- but not long-term melatonin administration reduces central levels of brain-derived neurotrophic factor in rats with inflammatory pain. PG - 358-64 LID - 10.1159/000380912 [doi] AB - OBJECTIVE: To evaluate the effect of short- and long-term administration of melatonin on central brain-derived neurotrophic factor (BDNF) levels in rats with acute and chronic inflammatory pain. METHODS: The animals were allocated to one of two experiments: experiment 1 or experiment 2. In experiment 1, all animals were injected with complete Freund's adjuvant (CFA) to induce inflammation and were randomly allocated to receiving melatonin (60 mg/kg) or vehicle. Injections were administered 1 h after CFA and once daily for 2 more days (for a total of 3 days of melatonin administration). In experiment 2, fifteen days after CFA injection, the animals were treated with melatonin (50 mg/kg) or vehicle for 8 days. The animals were killed by decapitation 24 h after the last melatonin or vehicle administration, and an ELISA assay was performed to detect BDNF expression in the spinal cord, brainstem, and prefrontal cortex of the rats in both groups. Data were analyzed using Student's t test and the results are expressed as means +/- SEM. RESULTS: In the first experiment, the BDNF levels of the melatonin group were reduced in the prefrontal cortex (Student's t test, p = 0.01) and increased in the spinal cord (Student's t test, p = 0.04). In experiment 2, BDNF levels were similar in both groups for all structures (Student's t test, p > 0.00 for all). A two-way ANOVA reveled a significant effect of structures (p = 0.0001) but not of treatment (p > 0.05). The prefrontal cortex presented higher BDNF levels than other structures (ANOVA/Student-Newman-Keuls test, p = 0.0001). Considering the relationship between BDNF levels in all three structures, we found an effect of central nervous system structures (p = 0.01) and an interaction between treatment and structures (p = 0.04). CONCLUSION: The high spinal cord BDNF levels and the low prefrontal cortical BDNF levels observed in rats with acute CFA-induced inflammation following short-term melatonin administration may be related to the pain-modulating and neuroprotective effects of this protein. Long-term melatonin administration did not alter BDNF levels in chronic inflammation. CI - (c) 2015 S. Karger AG, Basel. FAU - Laste, Gabriela AU - Laste G AD - Pain Pharmacology and Neuromodulation, Animal Models Laboratory, Pharmacology Department, Instituto de Cix00EA;ncias Bx00E1;sicas da Sax00FA;de, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. FAU - Ripoll Rozisky, Joanna AU - Ripoll Rozisky J FAU - Caumo, Wolnei AU - Caumo W FAU - Lucena da Silva Torres, Iraci AU - Lucena da Silva Torres I LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20150411 PL - Switzerland TA - Neuroimmunomodulation JT - Neuroimmunomodulation JID - 9422763 RN - 0 (Antioxidants) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 9007-81-2 (Freund's Adjuvant) RN - JL5DK93RCL (Melatonin) SB - IM MH - Analysis of Variance MH - Animals MH - Antioxidants/*therapeutic use MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Central Nervous System/drug effects/*metabolism MH - Chronic Disease MH - Disease Models, Animal MH - Freund's Adjuvant/toxicity MH - Inflammation/chemically induced/*complications MH - Melatonin/*therapeutic use MH - *Pain/drug therapy/etiology/metabolism MH - Rats MH - Time Factors EDAT- 2015/04/15 06:00 MHDA- 2016/08/16 06:00 CRDT- 2015/04/15 06:00 PHST- 2014/05/28 00:00 [received] PHST- 2015/02/11 00:00 [accepted] PHST- 2015/04/15 06:00 [entrez] PHST- 2015/04/15 06:00 [pubmed] PHST- 2016/08/16 06:00 [medline] AID - 000380912 [pii] AID - 10.1159/000380912 [doi] PST - ppublish SO - Neuroimmunomodulation. 2015;22(6):358-64. doi: 10.1159/000380912. Epub 2015 Apr 11.