[The impact and mechanism of glutamate transporter 1-mediated visceral nociception and hyperalgesia following exposure to post-traumatic stress disorder-like stress in spinal cord of rats].

OBJECTIVE

To investigate the expression of glutamate transporter 1 (GLT-1) and determine the effect of GLT-1 overexpression on the visceromotor response ( VMR ) to colorectal distention (CRD) following exposure to post-traumatic stress disorder (PTSD)-like stress.

METHODS

A beta-lactam antibiotic, ceftriaxone (CTX) was used to selectively induce transcription of the gene encoding GLT-1 and upregulate GLT-1 expression as an agonist. SD rats were divided into five groups, including control group, PTSD group, CTX-treated group, PTSD+CTX group, PTSD+CTX+ dihydrokainate (DHK) group. Seven rats in each VMR-CRD group eventually completed the study. Ten rats in each group were used to test immunofluorescence of GLT-1, however, 8, 9, 8, 10, 7 rats completed the test respectively. The animal model of PTSD was established using basal ovalbumin (OVA)-sensitization combined with single-prolonged stress model (SPS). The alteration of visceral sensitivity following exposure to PTSD-like stress was evaluated by measuring the VMR to CRD. Spinal GLT-1 expression was evaluated by immunofluorescence using confocal laser scanning microscopy.

RESULTS

By immunofluorescence analysis, CTX-treated rats exhibited an increased GLT-1 expression in spinal cord compared with the control group (absorbance: 141.38 ± 2.91 vs 106.25 ± 3.32, P = 0.001). Absorbance of GLT-1 in spinal cord was significantly decreased in PTSD rats, compared with the control rats (86.11 ± 2.73 vs 106.25 ± 3.32, P = 0.001). GLT-1 expression in PTSD rats treated with CTX was significantly increased compared with PTSD group (98.70 ± 3.19 vs 86.11 ± 2.73, P = 0.004 ). VMR to CRD significantly elevated in PTSD group compared with the control group at 20, 40, 60 and 80 mmHg (all P < 0.05, 1 mmHg = 0.133 kPa). VMR significantly declined in PTSD rats treated with CTX when compared with the vehicle at graded CRD pressure (all P < 0.01), however, one-hour pretreatment with selective GLT-1 antagonist dihydrokainate reversed the blunted VMR to CRD produced by CTX (P = 0.002). VMR significantly decreased in CTX group compared with the control group at 40, 60 and 80 mmHg (all P < 0.05).

CONCLUSIONS

The study suggests that the PTSD alters visceral sensitivity and GLT-1 overexpression mediated the analgesic effect of CTX following exposure to PTSD-like stress, identifying a specific molecular mechanism for visceral hypersensitivity which may pave the way for novel therapeutic strategies for PTSD-like conditions.