Lidocaine attenuates proinflammatory cytokine production induced by extracellular adenosine triphosphate in cultured rat microglia.

BACKGROUND

Our previous studies demonstrated that intrathecal lidocaine treatment could produce prolonged reversal of established hyperalgesia or allodynia, both induced by chronic constriction injury. Indeed, intrathecal lidocaine treatment remarkably suppressed the activation of p38 mitogen-activated protein kinase (MAPK) in hyperactive microglia. In the present study we suggest that lidocaine may act directly on the microglia and attenuate the release of cytokines.

METHODS

We assessed the influence of lidocaine on the levels of phospho-p38 MAPK, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6, and intracellular calcium triggered by extracellular adenosine triphosphate (ATP) in cultured rat microglia. Our experimental methods included Western blot, real-time reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, and calcium imaging.

RESULTS

We found that lidocaine (in a dose-dependent manner) significantly attenuated p38 MAPK activation triggered by 1 mM ATP, by inhibiting the transcription of 3 cytokine messenger RNAs and causing a decrease in their respective protein concentrations (TNF-alpha, IL-1beta, and IL-6, P < 0.05, vs. the ATP group). SB203580, an antagonist of P38, attenuated ATP-activated elevation in protein levels of TNF-alpha, IL-1beta, and IL-6 in the microglia. The high level of intracellular calcium ([Ca(2+)]i) that is induced by ATP was decreased by the addition of 10 mM lidocaine (P < 0.05 vs. the ATP group).

CONCLUSIONS

These findings indicate that lidocaine can directly act on microglia. Lidocaine, by inhibiting the increase of intracellular calcium, also inhibited p38 MAPK activation and attenuated the production of proinflammatory cytokines (including TNF-alpha, IL-1beta, and IL-6), which were triggered by extracellular ATP in cultured rat microglia.