Lidocaine attenuates the development of diabetic-induced tactile allodynia by inhibiting microglial activation

Naoko Suzuki, Maiko Hasegawa-Moriyama, Yoshika Takahashi, Yuji Kamikubo, Takashi Sakurai, Eiichi Inada
Anesthesia and Analgesia 2011, 113 (4): 941-6

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.

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