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Spinal microglial P2X4 receptor-brain-derived neurotrophic factor signaling regulates nicotine withdrawal-induced hyperalgesia.
Neuroreport. 2017 Apr 12; 28(6):339-347.N

Abstract

Nicotine withdrawal (NTW) has been shown to increase pain sensitivity. However, the pathogenesis of NTW-induced hyperalgesia syndrome is unknown. Microglial activation, with increased expression of the P2X4 receptor (P2X4R) and brain-derived neurotrophic factor (BDNF) as important markers, is associated with hyperalgesia; therefore, these markers may represent an unprecedented target to prevent hyperalgesia. In this study, we explored the contributions of spinal microglial P2X4R-BDNF signaling in NTW-induced hyperalgesia. Immunohistochemical analysis showed that spinal microglia were activated and that the P2X4R level was increased and colocalized with ionized calcium-binding adapter molecule 1 in NTW-induced hyperalgesia. Furthermore, we showed that microglial activation with NTW resulted in an increased expression of spinal P2X4R and an elevated release of BDNF. Intrathecal minocycline (a specific inhibitor of microglial activation) reversed thermal hyperalgesia as well as increased the spinal microglial P2X4R and BDNF levels induced by NTW. To the best of our knowledge, the present study provides evidence that spinal microglial P2X4R-BDNF signaling is critical for the development of NTW-induced hyperalgesia.

Authors+Show Affiliations

aJiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu Province bDepartment of Anesthesiology, Liaocheng People's Hospital, Liaocheng, Shandong cDepartment of Medicine, Hebei North University, Zhangjiakou, Hebei, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28306606

Citation

Zhang, Xiaodi, et al. "Spinal Microglial P2X4 Receptor-brain-derived Neurotrophic Factor Signaling Regulates Nicotine Withdrawal-induced Hyperalgesia." Neuroreport, vol. 28, no. 6, 2017, pp. 339-347.
Zhang X, Xu P, Li C, et al. Spinal microglial P2X4 receptor-brain-derived neurotrophic factor signaling regulates nicotine withdrawal-induced hyperalgesia. Neuroreport. 2017;28(6):339-347.
Zhang, X., Xu, P., Li, C., Zhu, W., Wu, S., Yu, A., Ding, Y., Wang, Q., & Zhang, Z. (2017). Spinal microglial P2X4 receptor-brain-derived neurotrophic factor signaling regulates nicotine withdrawal-induced hyperalgesia. Neuroreport, 28(6), 339-347. https://doi.org/10.1097/WNR.0000000000000769
Zhang X, et al. Spinal Microglial P2X4 Receptor-brain-derived Neurotrophic Factor Signaling Regulates Nicotine Withdrawal-induced Hyperalgesia. Neuroreport. 2017 Apr 12;28(6):339-347. PubMed PMID: 28306606.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Spinal microglial P2X4 receptor-brain-derived neurotrophic factor signaling regulates nicotine withdrawal-induced hyperalgesia. AU - Zhang,Xiaodi, AU - Xu,Pengcheng, AU - Li,Chengbao, AU - Zhu,Wenchao, AU - Wu,Shanshan, AU - Yu,Ailan, AU - Ding,Yonghong, AU - Wang,Qinghe, AU - Zhang,Zongwang, PY - 2017/3/18/pubmed PY - 2018/1/11/medline PY - 2017/3/18/entrez SP - 339 EP - 347 JF - Neuroreport JO - Neuroreport VL - 28 IS - 6 N2 - Nicotine withdrawal (NTW) has been shown to increase pain sensitivity. However, the pathogenesis of NTW-induced hyperalgesia syndrome is unknown. Microglial activation, with increased expression of the P2X4 receptor (P2X4R) and brain-derived neurotrophic factor (BDNF) as important markers, is associated with hyperalgesia; therefore, these markers may represent an unprecedented target to prevent hyperalgesia. In this study, we explored the contributions of spinal microglial P2X4R-BDNF signaling in NTW-induced hyperalgesia. Immunohistochemical analysis showed that spinal microglia were activated and that the P2X4R level was increased and colocalized with ionized calcium-binding adapter molecule 1 in NTW-induced hyperalgesia. Furthermore, we showed that microglial activation with NTW resulted in an increased expression of spinal P2X4R and an elevated release of BDNF. Intrathecal minocycline (a specific inhibitor of microglial activation) reversed thermal hyperalgesia as well as increased the spinal microglial P2X4R and BDNF levels induced by NTW. To the best of our knowledge, the present study provides evidence that spinal microglial P2X4R-BDNF signaling is critical for the development of NTW-induced hyperalgesia. SN - 1473-558X UR - https://www.unboundmedicine.com/medline/citation/28306606/Spinal_microglial_P2X4_receptor_brain_derived_neurotrophic_factor_signaling_regulates_nicotine_withdrawal_induced_hyperalgesia_ L2 - https://doi.org/10.1097/WNR.0000000000000769 DB - PRIME DP - Unbound Medicine ER -