Lidocaine Attenuates the Development of Diabetic-Induced Tactile Allodynia by Inhibiting Microglial Activation

• DOI: 10.1213/ane.0b013e31822827a2
• Publication Date: 2011-07-26T08:24:06Z
• Authors: Naoko Suzuki; Maiko Hasegawa-Mo...; Yoshika Takahashi; Yuji Kamikubo; Takashi Sakurai; Eiichi Inada
• Keywords: Male; Pain Threshold; Behavior, Animal; Chemotaxis; Interleukin-1beta; Lidocaine; Nitric Oxide Synthase Type II; Diabetes Mellitus, Experimental; 3. Good health; Mice, Inbred C57BL; Interferon-gamma; Mice; 03 medical and health sciences; 0302 clinical medicine; Diabetic Neuropathies; Hyperalgesia; Animals; Infusions, Parenteral; Microglia; Anesthetics, Local; Cells, Cultured; Chemokine CCL2; Pain Measurement

Lidocaine is used clinically for tactile allodynia associated with diabetes-induced neuropathy. Although the analgesic effect of lidocaine through suppression of microglial activation has been implicated in the development of injury-induced neuropathic pain, its mechanism of action in diabetes-induced tactile allodynia has not yet been completely elucidated.To evaluate the effects of lidocaine on microglial response in diabetic neuropathy, streptozotocin (STZ)-injected mice received a continuous infusion of lidocaine (vehicle, 2, or 10%) from day 14 to day 21 after STZ injection. On day 21, microglial accumulation and p38 mitogen-activated protein kinase activation in the dorsal horn were evaluated. In vitro, the effects of lidocaine on cell viability, chemotactic response to monocyte chemotactic protein-1, and induction of proinflammatory mediators were examined in interferon (IFN)-γ-stimulated primary microglial cells.Continuous systemic administration of lidocaine in the early progression of tactile allodynia produced long-lasting analgesic effects in STZ-treated mice. Lidocaine significantly reduced accumulation and p38 phosphorylation of microglial cells in the dorsal horn. In vitro, lidocaine down-regulated IFN-γ-induced gene induction of inducible oxide synthase and interleukin-1β. Pretreatment with lidocaine significantly reduced chemotactic response to monocyte chemotactic protein-1 of IFN-γ-activated microglial cells.Lidocaine alleviates STZ-induced tactile allodynia, possibly by modulating the p38 pathway in spinal microglial cells. Inhibiting microglial activation by lidocaine treatment early in the course of diabetes-induced neuropathy represents a potential therapeutic strategy for tactile allodynia.