Reactive microglia after taste nerve injury: comparison to nerve injury models of chronic pain

Abstract

The chorda tympani (CT), which innervates taste buds on the anterior portion of the tongue, is susceptible to damage during inner ear surgeries. Injury to the CT causes a disappearance of taste buds, which is concurrent with significant microglial responses at central nerve terminals in the nucleus of the solitary tract (nTS). The resulting taste disturbances that can occur may persist for months or years, long after the nerve and taste buds have regenerated. These persistent changes in taste sensation suggest alterations in central functioning and may be related to the microglial responses. This is reminiscent of nerve injuries that result in chronic pain, where microglial reactivity is essential in maintaining the altered sensation (i.e., pain). In these models, methods that diminish microglial responses also diminish the corresponding pain behavior. Although the CT nerve does not contain nociceptive pain fibers, the microglial reactivity after CT damage is similar to that described in pain models. Therefore, methods that decrease microglial responses in pain models were used here to test if they could also affect microglial reactivity after CT injury. Treatment with minocycline, an antibiotic that dampens pain responsive microglia, was largely ineffective in diminishing microglial responses after CT injury. In addition, signaling through the toll-like 4 receptor (TLR4) does not seem to be required after CT injury as blocking or deleting TLR4 had no effect on microglial reactivity. These results suggest that microglial responses following CT injury rely on different signaling mechanisms than those described in nerve injuries resulting in chronic pain.