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

Background

Inhibition of astrocytic energy metabolism alleviates neuropathic pain.

Objectives

To explore whether astrocyte-neuron lactate shuttle (ANLS) played any role in neuropathic orofacial pain.

Methods

Rats 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.

Results

Compared 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.

Conclusions

Inhibition of ANLS alleviates p-IONX-related neuronal, behavioural and immunohistochemical changes, which suggests that ANLS plays an important role in trigeminal neuropathic pain.