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

Abstract

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.

• Authors: Ya-Feng Zhou, Xiao-Ming Ying, Xiao-Fen He, Sheng-Yun Shou, Jun-Jun Wei, Zhao-Xia Tai, Xiao-Mei Shao, Yi Liang, Fang Fang, Jian-Qiao Fang, Yong-Liang Jiang
• Journal: Purinergic signalling (Purinergic Signal) Vol. 14 Issue 4 Pg. 359-369 (12 2018) ISSN: 1573-9546 [Electronic] Netherlands
• PMID: 30084084 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Purinergic P2X Receptor Antagonists
• Receptors for Activated C Kinase
• Receptors, Purinergic P2X3

Topics

• Animals
• Diabetes Mellitus, Experimental (metabolism)
• Diabetic Neuropathies (metabolism)
• Ganglia, Spinal (metabolism)
• Neuralgia (metabolism)
• Purinergic P2X Receptor Antagonists (pharmacology)
• Rats, Sprague-Dawley
• Receptors for Activated C Kinase (drug effects, metabolism)
• Receptors, Purinergic P2X3 (drug effects, metabolism)
• Up-Regulation