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The implication of transient receptor potential canonical 6 in BDNF-induced mechanical allodynia in rat model of diabetic neuropathic pain.
Life Sci. 2021 May 15; 273:119308.LS

Abstract

AIMS

Brain-derived neurotrophic factor (BDNF) is vital in the pathogenesis of mechanical allodynia with a paucity of reports available regarding diabetic neuropathy pain (DNP). Herein we identified the involvement of BDNF in driving mechanical allodynia in DNP rats via the activation of transient receptor potential canonical 6 (TRPC6) channel.

MATERIALS AND METHODS

The DNP rat model was established via streptozotocin (STZ) injection, and allodynia was assessed by paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL). The expression profiles of BDNF and TRPC6 in dorsal root ganglia (DRG) and spinal cord were illustrated by immunofluorescence and Western blotting. Intrathecal administration of K252a or TrkB-Fc was performed to inhibit BNDF/TrkB expression, and respective injection of GsMTX-4, BTP2 and TRPC6 antisense oligodeoxynucleotides (TRPC6-AS) was likewise conducted to inhibit TRPC6 expression in DNP rats. Calcium influx in DRG was monitored by calcium imaging.

KEY FINDINGS

The time-dependent increase of BDNF and TRPC6 expression in DRG and spinal cord was observed since the 7th post-STZ day, correlated with the development of mechanical allodynia in DNP rats. Intrathecal administration of K252a, TrkB-Fc, GsMTX-4 and BTP2 prevented mechanical allodynia in DNP rats. Pre-treatment of TRPC6-AS reversed the BDNF-induced pain-like responses in DNP rats rather than the naïve rats. In addition, the TRPC6-AS reversed BDNF-induced increase of calcium influx in DRG neurons in DNP rats.

SIGNIFICANCE

The intrathecal inhibition of TRPC6 alleviated the BDNF-induced mechanical allodynia in DNP rat model. This finding may validate the application of TRPC6 antagonists as interesting strategy for DNP management.

Authors+Show Affiliations

Department of Gastroenterology, The Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou 221002, Jiangsu Province, China; Institute of Digestive Diseases, Xuzhou Medical University, 84 West Huaihai Road, Xuzhou 221002, Jiangsu Province, China.Department of Anesthesiology, Xuzhou Central Hospital, 199 Jiefang South Road, Xuzhou 221009, Jiangsu Province, China.Department of Pathology, Xinyi People's Hospital, 16 Renmin Road, Xinyi 221400, Jiangsu Province, China.Department of Gastroenterology, The Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou 221002, Jiangsu Province, China.Department of Gastroenterology, The Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou 221002, Jiangsu Province, China.Central Laboratory, The Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou 221002, Jiangsu Province, China. Electronic address: shl@xzhmu.edu.cn.Department of Gastroenterology, The Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou 221002, Jiangsu Province, China; Institute of Digestive Diseases, Xuzhou Medical University, 84 West Huaihai Road, Xuzhou 221002, Jiangsu Province, China. Electronic address: xyfyfeisj99@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33667520

Citation

Miao, Bei, et al. "The Implication of Transient Receptor Potential Canonical 6 in BDNF-induced Mechanical Allodynia in Rat Model of Diabetic Neuropathic Pain." Life Sciences, vol. 273, 2021, p. 119308.
Miao B, Yin Y, Mao G, et al. The implication of transient receptor potential canonical 6 in BDNF-induced mechanical allodynia in rat model of diabetic neuropathic pain. Life Sci. 2021;273:119308.
Miao, B., Yin, Y., Mao, G., Zhao, B., Wu, J., Shi, H., & Fei, S. (2021). The implication of transient receptor potential canonical 6 in BDNF-induced mechanical allodynia in rat model of diabetic neuropathic pain. Life Sciences, 273, 119308. https://doi.org/10.1016/j.lfs.2021.119308
Miao B, et al. The Implication of Transient Receptor Potential Canonical 6 in BDNF-induced Mechanical Allodynia in Rat Model of Diabetic Neuropathic Pain. Life Sci. 2021 May 15;273:119308. PubMed PMID: 33667520.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The implication of transient receptor potential canonical 6 in BDNF-induced mechanical allodynia in rat model of diabetic neuropathic pain. AU - Miao,Bei, AU - Yin,Yue, AU - Mao,Guangtong, AU - Zhao,Benhuo, AU - Wu,Jiaojiao, AU - Shi,Hengliang, AU - Fei,Sujuan, Y1 - 2021/03/02/ PY - 2020/12/14/received PY - 2021/02/18/revised PY - 2021/02/21/accepted PY - 2021/3/6/pubmed PY - 2021/3/6/medline PY - 2021/3/5/entrez KW - Brain-derived neurotrophic factor KW - Diabetic neuropathy pain KW - Dorsal root ganglion KW - Mechanical allodynia KW - Transient receptor potential canonical 6 channel SP - 119308 EP - 119308 JF - Life sciences JO - Life Sci VL - 273 N2 - AIMS: Brain-derived neurotrophic factor (BDNF) is vital in the pathogenesis of mechanical allodynia with a paucity of reports available regarding diabetic neuropathy pain (DNP). Herein we identified the involvement of BDNF in driving mechanical allodynia in DNP rats via the activation of transient receptor potential canonical 6 (TRPC6) channel. MATERIALS AND METHODS: The DNP rat model was established via streptozotocin (STZ) injection, and allodynia was assessed by paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL). The expression profiles of BDNF and TRPC6 in dorsal root ganglia (DRG) and spinal cord were illustrated by immunofluorescence and Western blotting. Intrathecal administration of K252a or TrkB-Fc was performed to inhibit BNDF/TrkB expression, and respective injection of GsMTX-4, BTP2 and TRPC6 antisense oligodeoxynucleotides (TRPC6-AS) was likewise conducted to inhibit TRPC6 expression in DNP rats. Calcium influx in DRG was monitored by calcium imaging. KEY FINDINGS: The time-dependent increase of BDNF and TRPC6 expression in DRG and spinal cord was observed since the 7th post-STZ day, correlated with the development of mechanical allodynia in DNP rats. Intrathecal administration of K252a, TrkB-Fc, GsMTX-4 and BTP2 prevented mechanical allodynia in DNP rats. Pre-treatment of TRPC6-AS reversed the BDNF-induced pain-like responses in DNP rats rather than the naïve rats. In addition, the TRPC6-AS reversed BDNF-induced increase of calcium influx in DRG neurons in DNP rats. SIGNIFICANCE: The intrathecal inhibition of TRPC6 alleviated the BDNF-induced mechanical allodynia in DNP rat model. This finding may validate the application of TRPC6 antagonists as interesting strategy for DNP management. SN - 1879-0631 UR - https://www.unboundmedicine.com/medline/citation/33667520/The_implication_of_transient_receptor_potential_canonical_6_in_BDNF_induced_mechanical_allodynia_in_rat_model_of_diabetic_neuropathic_pain_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(21)00293-9 DB - PRIME DP - Unbound Medicine ER -