PMID- 29409869 OWN - NLM STAT- MEDLINE DCOM- 20180301 LR - 20180301 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 197 DP - 2018 Mar 15 TI - The role of hippocampal brain-derived neurotrophic factor in age-related differences in neuropathic pain behavior in rats. PG - 56-66 LID - S0024-3205(18)30042-0 [pii] LID - 10.1016/j.lfs.2018.01.030 [doi] AB - AIMS: This study was aimed to explore the contribution of central brain-derived neurotrophic factor (BDNF) in the neuropathic pain pathogenesis using an aged rodent model. MAIN METHODS: Adult and aged rats were randomly assigned to either a sciatic nerve ligation (SNL) group or a control skin sham surgery group. Sensory behavioral testing were performed on the day before surgery and on the 3rd, 7th, 14th, and 21st days after surgery, followed by measurement of BDNF protein levels in different brain regions. In another experiment, the hippocampal BDNF gene expression after SNL surgery was assessed at different time-points. Furthermore, the analgesic effects of intranasal BDNF administration were tested in SNL animals. KEY FINDINGS: Our behavioral results demonstrated that the hyperalgesia-like behavior after painful nerve injury has a higher incidence in aged rats compared with in adult animals. In particular, the hippocampal BDNF levels were inversely correlated with the probability of hyperalgesia-type behavior, in both brain-region specific and age-dependent manner. Time-course analysis showed that the hippocampal levels of BDNF mRNA in aged and adult rats started to decrease 7 and 14 days after surgery, respectively. However, the decrease was more pronounced in aged animals. Moreover, the repeated intranasal BDNF treatment could restore the central BDNF signaling, counteracting the age-related exacerbation of hyperalgesic behavior. SIGNIFICANCE: Our findings imply that hippocampal BDNF may be related with the pathogenesis of elderly neuropathic pain. Pharmacological data further suggest that brain BDNF may be modifiable in aged neuropathic animals, and therefore, represent a promising target for intervention. CI - Copyright (c) 2018 Elsevier Inc. All rights reserved. FAU - Tateiwa, Hiroki AU - Tateiwa H AD - Department of Anesthesiology and Intensive Care Medicine, Kochi Medical School, Nankoku, Kochi, Japan. FAU - Kawano, Takashi AU - Kawano T AD - Department of Anesthesiology and Intensive Care Medicine, Kochi Medical School, Nankoku, Kochi, Japan. Electronic address: takashika@kochi-u.ac.jp. FAU - Nishigaki, Atsushi AU - Nishigaki A AD - Department of Anesthesiology and Intensive Care Medicine, Kochi Medical School, Nankoku, Kochi, Japan. FAU - Yamanaka, Daiki AU - Yamanaka D AD - Department of Anesthesiology and Intensive Care Medicine, Kochi Medical School, Nankoku, Kochi, Japan. FAU - Aoyama, Bun AU - Aoyama B AD - Department of Anesthesiology and Intensive Care Medicine, Kochi Medical School, Nankoku, Kochi, Japan. FAU - Shigematsu-Locatelli, Marie AU - Shigematsu-Locatelli M AD - Department of Anesthesiology and Intensive Care Medicine, Kochi Medical School, Nankoku, Kochi, Japan. FAU - Eguchi, Satoru AU - Eguchi S AD - Department of Dental Anesthesiology, Tokushima University School of Dentistry, Tokushima, Japan. FAU - Locatelli, Fabricio M AU - Locatelli FM AD - Department of Anesthesiology and Intensive Care Medicine, Kochi Medical School, Nankoku, Kochi, Japan. FAU - Yokoyama, Masataka AU - Yokoyama M AD - Department of Anesthesiology and Intensive Care Medicine, Kochi Medical School, Nankoku, Kochi, Japan. LA - eng PT - Journal Article DEP - 20180201 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (RNA, Messenger) SB - IM MH - Aging/*metabolism/pathology MH - Animals MH - *Behavior, Animal MH - Brain-Derived Neurotrophic Factor/*biosynthesis MH - *Gene Expression Regulation MH - Hippocampus/*metabolism/pathology MH - Male MH - Neuralgia/*metabolism/pathology MH - RNA, Messenger/biosynthesis MH - Rats MH - Rats, Wistar OTO - NOTNLM OT - Aging OT - BDNF OT - Chronic pain OT - Hippocampus OT - Neuropathic pain EDAT- 2018/02/08 06:00 MHDA- 2018/03/02 06:00 CRDT- 2018/02/08 06:00 PHST- 2017/10/27 00:00 [received] PHST- 2018/01/16 00:00 [revised] PHST- 2018/01/30 00:00 [accepted] PHST- 2018/02/08 06:00 [pubmed] PHST- 2018/03/02 06:00 [medline] PHST- 2018/02/08 06:00 [entrez] AID - S0024-3205(18)30042-0 [pii] AID - 10.1016/j.lfs.2018.01.030 [doi] PST - ppublish SO - Life Sci. 2018 Mar 15;197:56-66. doi: 10.1016/j.lfs.2018.01.030. Epub 2018 Feb 1.