The Role of Astrocyte‐Neuron Lactate Shuttle in Neuropathic Orofacial Pain

Abstract

ABSTRACTBackgroundInhibition of astrocytic energy metabolism alleviates neuropathic pain.ObjectivesTo explore whether astrocyte‐neuron lactate shuttle (ANLS) played any role in neuropathic orofacial pain.MethodsRats with partial transection of the right infraorbital nerve (p‐IONX) or sham operation were intrathecally injected with acetazolamide (a carbonic anhydrase inhibitor), bithionol (a soluble adenylyl cyclase inhibitor), α‐cyano‐4‐hydroxycinnamic acid [α‐CHCA, a monocarboxylate transporter (MCT) inhibitor] or vehicle once a day from postoperative day 1–14. The facial mechanical thresholds were tested on preoperative day 1 and 2 and postoperative days 1, 3, 5, 7, 10 and 14, expression of glucose transporters (GLUTs) and MCTs in the trigeminal subnucleus caudalis (Vc) were examined on the postoperative day 3 and neuronal activities in the Vc were examined in the p‐IONX rats on postoperative days 3–5.ResultsCompared with the sham group, the mechanical thresholds in the p‐IONX group were significantly reduced at postoperative days 1–7, and the number of astrocytes expressing GLUT1 and MCT1/4, and neurons expressing MCT2 was significantly increased on postoperative day 3. In the p‐IONX groups, neurons in the Vc were sensitised, and acetazolamide, bithionol and α‐CHCA reversed the central sensitisation, significantly increased the mechanical thresholds at postoperative days 1–7 and decreased the number of astrocytes expressing GLUT1 and MCT1/4, and neurons expressing MCT2 at postoperative day 3 compared with those in the vehicle‐treated rats.ConclusionsInhibition of ANLS alleviates p‐IONX‐related neuronal, behavioural and immunohistochemical changes, which suggests that ANLS plays an important role in trigeminal neuropathic pain.