Suppressing PKC-dependent membrane P2X3 receptor upregulation in dorsal root ganglia mediated electroacupuncture analgesia in rat painful diabetic neuropathy

• Published in: Purinergic signalling Vol. 14; no. 4; pp. 359 - 369
• Main Authors: Zhou, Ya-feng, Ying, Xiao-ming, He, Xiao-fen, Shou, Sheng-Yun, Wei, Jun-Jun, Tai, Zhao-xia, Shao, Xiao-mei, Liang, Yi, Fang, Fang, Fang, Jian-qiao, Jiang, Yong-liang
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.12.2018; Springer Nature B.V
• Subjects: Acetic acid; Acupuncture; Analgesia; Analgesics; Animals; Biomedical and Life Sciences; Biomedicine; Blood glucose; Body weight; Cancer Research; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - metabolism; Diabetic Neuropathies - metabolism; Diabetic neuropathy; Dorsal root ganglia; Fasting; Feeding; Ganglia, Spinal - metabolism; High fat diet; Human Physiology; Insulin; Kinases; Neuralgia - metabolism; Neurosciences; Original; Original Article; Pain; Pain perception; Peripheral neuropathy; Pharmacology/Toxicology; Phorbol 12-myristate 13-acetate; Protein kinase C; Purinergic P2X Receptor Antagonists - pharmacology; Rats, Sprague-Dawley; Receptors for Activated C Kinase - drug effects; Receptors for Activated C Kinase - metabolism; Receptors, Purinergic P2X3 - drug effects; Receptors, Purinergic P2X3 - metabolism; Sciatic nerve; Streptozocin; Sugar; Up-Regulation; Painful diabetic neuropathy (PDN); Dorsal root ganglia (DRG); Electroacupuncture (EA); Protein kinase C (PKC); P2X3 receptor
• DOI: 10.1007/s11302-018-9617-4
• ISSN: 1573-9538; 1573-9546

Painful diabetic neuropathy (PDN) is a common and troublesome diabetes complication. Protein kinase C (PKC)-mediated dorsal root ganglia (DRG) P2X3 receptor upregulation is one important mechanism underlying PDN. Accumulating evidence demonstrated that electroacupuncture (EA) at low frequency could effectively attenuate neuropathic pain. Our previous study showed that 2-Hz EA could relieve pain well in PDN. The study aimed to investigate whether 2-Hz EA relieves pain in PDN through suppressing PKC-mediated DRG P2X3 receptor upregulation. A 7-week feeding of high-fat and high-sugar diet plus a single injection of streptozotocin (STZ) in a dose of 35 mg/kg after a 5-week feeding of the diet successfully induced type 2 PDN in rats as revealed by the elevated body weight, fasting blood glucose, fasting insulin and insulin resistance, and the reduced paw withdrawal threshold (PWT), as well as the destructive ultrastructural change of sciatic nerve. DRG plasma membrane P2X3 receptor level and DRG PKC expression were elevated. Two-hertz EA failed to improve peripheral neuropathy; however, it reduced PWT, DRG plasma membrane P2X3 receptor level, and DRG PKC expression in PDN rats. Intraperitoneal administration of P2X3 receptor agonist αβ-meATP or PKC activator phorbol 12-myristate 13-acetate (PMA) blocked 2-Hz EA analgesia. Furthermore, PMA administration increased DRG plasma membrane P2X3 receptor level in PDN rats subject to 2-Hz EA treatment. These findings together indicated that the analgesic effect of EA in PDN is mediated by suppressing PKC-dependent membrane P2X3 upregulation in DRG. EA at low frequency is a valuable approach for PDN control.