TRESK alleviates trigeminal neuralgia induced by infraorbital nerve chronic constriction injury in rats

Abstract

Trigeminal neuralgia commonly results in pain behaviors and cognitive impairment. Convincing evidence suggests that TWIK-related spinal cord K⁺ (TRESK) exerts antinociceptive and neuroprotective effects. However, its possible potentials in trigeminal neuralgia remain unclear. Trigeminal neuralgia model was established in rats by generating an infraorbital nerve chronic constriction injury, and rats received intrathecal injections of TRESK-overexpressing lentivirus and siRNA expression vector-targeted against TRESK (si-TRESK) into the trigeminal ganglions. Mechanical allodynia was evaluated by mechanical withdrawal threshold. Cognitive capacity was tested using Morris water maze. The TRESK expression was determined by quantitative real-time polymerase chain reaction and Western blotting. Results showed that the mRNA and protein levels of TRESK were significantly downregulated in trigeminal ganglions in injured rats. Intrathecal treatment with TRESK reduced mechanical allodynia and relieved learning and memory deficits in trigeminal neuralgia rats, while si-TRESK injection caused neuropathic pain and cognitive deficits. In summary, the present study concluded that TRESK ameliorated pain-associated behaviors and cognitive deficits, which was useful as an alternative approach in management of trigeminal neuralgia.

Keywords: Cognitive impairment; TWIK-related spinal cord K+; infraorbital nerve chronic constriction injury; neuropathic pain; trigeminal neuralgia.

Figure 1.

TRESK expression in trigeminal ganglions in trigeminal neuropathic rats. The mRNA (a) and protein levels (b) of TRESK in trigeminal ganglions preoperatively and at postoperative 1, 7, 15 and 30 days in sham-operated rats and ION-CCI rats determined by qRT-PCR and Western blotting. *P < 0.05 versus sham group. n = 3 in each time point. GAPDH: glyceraldehyde 3-phosphate dehydrogenase; ION-CCI: infraorbital nerve chronic constriction injury; TRESK: TWIK-related spinal cord K⁺.

Figure 2.

TRESK expression in trigeminal ganglions after intrathecal injection of LV-TRESK. (a) Time course of MWT, the escape latency (b), and swimming speed (c) at different time points in the groups of control, sham, ION-CCI, LV-NC, and LV-TRESK. The mRNA (d) and protein levels (e) of TRESK in trigeminal ganglions at postoperative d28 in the groups of control, sham, ION-CCI, LV-NC, and LV-TRESK. *P < 0.05 versus sham; ^&P < 0.05 and ^$P<0.05 versus LV-NC; ^#P < 0.05 versus pre-op; ns, no significance. n = 6 in each group. GAPDH: glyceraldehyde 3-phosphate dehydrogenase; ION-CCI: infraorbital nerve chronic constriction injury; LV-NC: a negative control lentiviral vector; LV-TRESK: TRESK-overexpressing lentivirus; MWT: mechanical withdrawal threshold; TRESK: TWIK-related spinal cord K⁺.

Figure 3.

TRESK expression in trigeminal ganglions after intrathecal injection of si-TRESK. (a) Time course of MWT, the escape latency (b), and swimming speed (c) at different time points in the groups of control, siRNA, and si-TRESK. The mRNA (d) and protein levels (E) of TRESK in trigeminal ganglions at postoperative d35 in the groups of control, siRNA, and si-TRESK. ^$P < 0.05 versus siRNA group; ^&P<0.05 versus si-TRESK group; ns, no significance. n = 6 in each group. GAPDH: glyceraldehyde 3-phosphate dehydrogenase; MWT: mechanical withdrawal threshold; TRESK: TWIK-related spinal cord K⁺; si-TRESK: siRNA expression vector-targeted against TRESK.