Role of CNS Acid Sphingomyelinase on Allodynia in Mice

Objectives: Sphingolipids such as ceramide, ceramide 1-phosphate, sphingosine play an important role in neuronal signaling. It is, however, unclear whether CNS sphingolipids could play a role in nociception. The present study was carried out to elucidate possible effects of CNS ASMase in neuronal signaling in carrageenan induced orofacial pain. Methods: Balb/c mice received intracerebroventricular (ICV) injection of inhibitors to ASMase and unilateral facial carrageenan injection. The number of unilateral facial wash responses to mechanical stimulation of the carrageenan injected area of the face using a Von Frey Hair was quantified at various time intervals - before injections, and at 6 h, 1 day and 3 days after injections. Results: Increased number of face wash strokes after Von Frey hair stimulation was observed after facial carrageenan injection, indicating allodynia or hyperalgesia, but this increase was attenuated 3 days after ICV injection of the ASMase inhibitors, D609 or PtdIns3,5P2. Significantly increased activity of ASMase was detected in the thalamus on the side contralateral to the facial carrageenan injection, but not the brainstem or cerebral cortex using a fluorescence-based enzyme activity assay. Conclusion: The above findings suggest that facial carrageenan injection may activate ASMase enzymatic activity in the thalamus resulting in hyperalgesia, and point to a role of CNS sphingolipids in nociception. Supported by the Academic Research Fund, National University of Singapore.