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BDNF contributes to the neonatal incision-induced facilitation of spinal long-term potentiation and the exacerbation of incisional pain in adult rats.
Neuropharmacology. 2018 07 15; 137:114-132.N

Abstract

Neonatal surgical injury exacerbates spinal microglial reactivity, modifies spinal synaptic function, leading to exaggerated pain hypersensitivity after adult repeated incision. Whether and how the alteration in microglial reactivity and synaptic plasticity are functionally related remain unclear. Previously, we and others have documented that spinal brain-derived neurotrophic factor (BDNF), secreted from microglia, contributes to long-term potentiation (LTP) in adult rodents with neuropathic pain. Here, we demonstrated that the mRNA and protein expression of spinal BDNF are significantly upregulated in adult rats subjected to neonatal incision and adult repeated incision (nIN-IN). Neonatal incision facilitates spinal LTP induced by BDNF or high frequency electrical stimulation after adult incision, including a decreased induction threshold and an increased magnitude of LTP. Coincidently, inhibition of spinal BDNF abrogates the LTP facilitation, alleviates the mechanical allodynia and thermal hyperalgesia in nIN-IN rats. By contrast, spinal application of exogenous BDNF in the adult rats with a single neonatal incision mimics the LTP facilitation and pain hypersensitivity, which have been found in nIN-IN rats. Exogenous BDNF-induced exacerbation of pain hypersensitivity could be blocked by BDNF inhibitor. In addition, blockade of microglial reactivity by intrathecal application of minocycline attenuates the elevation of BDNF and the LTP facilitation, and also, alleviates pain hypersensitivity in nIN-IN rats. In conclusion, spinal BDNF, at least partly derived from microglia, contributes to the neonatal incision-induced facilitation of spinal LTP and to the exacerbation of incisional pain in adult rats. Thus, spinal BDNF may combine the changes of microglial reactivity and synaptic plasticity in nIN-IN rats.

Authors+Show Affiliations

Nutrition Research Unit, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China. Electronic address: dingxu@bjmu.edu.cn.Department of Neurobiology, School of Basic Medical Sciences and Neuroscience Research Institute, Peking University, Key Lab for Neuroscience, Ministry of Education of China and National Committee of Health and Family Planning of China, Peking University, Beijing 100083, China. Electronic address: liangyajing6@163.com.Center of Medical and Health Analysis, Peking University, Beijing, China. Electronic address: suli76@sina.com.Department of Neurobiology, School of Basic Medical Sciences and Neuroscience Research Institute, Peking University, Key Lab for Neuroscience, Ministry of Education of China and National Committee of Health and Family Planning of China, Peking University, Beijing 100083, China. Electronic address: emailliaoff@163.com.Department of Neurobiology, School of Basic Medical Sciences and Neuroscience Research Institute, Peking University, Key Lab for Neuroscience, Ministry of Education of China and National Committee of Health and Family Planning of China, Peking University, Beijing 100083, China. Electronic address: fangdongpain@sina.com.Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China. Electronic address: taibech@sina.com.Department of Neurobiology, School of Basic Medical Sciences and Neuroscience Research Institute, Peking University, Key Lab for Neuroscience, Ministry of Education of China and National Committee of Health and Family Planning of China, Peking University, Beijing 100083, China. Electronic address: ggxing@bjmu.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29729892

Citation

Ding, Xu, et al. "BDNF Contributes to the Neonatal Incision-induced Facilitation of Spinal Long-term Potentiation and the Exacerbation of Incisional Pain in Adult Rats." Neuropharmacology, vol. 137, 2018, pp. 114-132.
Ding X, Liang YJ, Su L, et al. BDNF contributes to the neonatal incision-induced facilitation of spinal long-term potentiation and the exacerbation of incisional pain in adult rats. Neuropharmacology. 2018;137:114-132.
Ding, X., Liang, Y. J., Su, L., Liao, F. F., Fang, D., Tai, J., & Xing, G. G. (2018). BDNF contributes to the neonatal incision-induced facilitation of spinal long-term potentiation and the exacerbation of incisional pain in adult rats. Neuropharmacology, 137, 114-132. https://doi.org/10.1016/j.neuropharm.2018.04.032
Ding X, et al. BDNF Contributes to the Neonatal Incision-induced Facilitation of Spinal Long-term Potentiation and the Exacerbation of Incisional Pain in Adult Rats. Neuropharmacology. 2018 07 15;137:114-132. PubMed PMID: 29729892.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - BDNF contributes to the neonatal incision-induced facilitation of spinal long-term potentiation and the exacerbation of incisional pain in adult rats. AU - Ding,Xu, AU - Liang,Ya-Jing, AU - Su,Li, AU - Liao,Fei-Fei, AU - Fang,Dong, AU - Tai,Jun, AU - Xing,Guo-Gang, Y1 - 2018/05/03/ PY - 2018/01/04/received PY - 2018/04/08/revised PY - 2018/04/29/accepted PY - 2018/5/8/pubmed PY - 2019/3/21/medline PY - 2018/5/7/entrez KW - Brain-derived neurotrophic factor KW - Incisional pain KW - Long-term potentiation KW - Neonatal rat KW - Spinal dorsal horn SP - 114 EP - 132 JF - Neuropharmacology JO - Neuropharmacology VL - 137 N2 - Neonatal surgical injury exacerbates spinal microglial reactivity, modifies spinal synaptic function, leading to exaggerated pain hypersensitivity after adult repeated incision. Whether and how the alteration in microglial reactivity and synaptic plasticity are functionally related remain unclear. Previously, we and others have documented that spinal brain-derived neurotrophic factor (BDNF), secreted from microglia, contributes to long-term potentiation (LTP) in adult rodents with neuropathic pain. Here, we demonstrated that the mRNA and protein expression of spinal BDNF are significantly upregulated in adult rats subjected to neonatal incision and adult repeated incision (nIN-IN). Neonatal incision facilitates spinal LTP induced by BDNF or high frequency electrical stimulation after adult incision, including a decreased induction threshold and an increased magnitude of LTP. Coincidently, inhibition of spinal BDNF abrogates the LTP facilitation, alleviates the mechanical allodynia and thermal hyperalgesia in nIN-IN rats. By contrast, spinal application of exogenous BDNF in the adult rats with a single neonatal incision mimics the LTP facilitation and pain hypersensitivity, which have been found in nIN-IN rats. Exogenous BDNF-induced exacerbation of pain hypersensitivity could be blocked by BDNF inhibitor. In addition, blockade of microglial reactivity by intrathecal application of minocycline attenuates the elevation of BDNF and the LTP facilitation, and also, alleviates pain hypersensitivity in nIN-IN rats. In conclusion, spinal BDNF, at least partly derived from microglia, contributes to the neonatal incision-induced facilitation of spinal LTP and to the exacerbation of incisional pain in adult rats. Thus, spinal BDNF may combine the changes of microglial reactivity and synaptic plasticity in nIN-IN rats. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/29729892/BDNF_contributes_to_the_neonatal_incision_induced_facilitation_of_spinal_long_term_potentiation_and_the_exacerbation_of_incisional_pain_in_adult_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(18)30193-X DB - PRIME DP - Unbound Medicine ER -