Amitriptyline upregulates EAAT1 and EAAT2 in neuropathic pain rats

Excitatory amino acid transporters (EAATs) appear to participate in the pathogenesis of neuropathic pain. The present study was performed to evaluate the effects of the tricyclic antidepressant amitriptyline on the expressions of EAATs in neuropathic pain rats. Using spared nerve injured (SNI) male Sprague Dawley rats, we found that SNI induced an initial EAATs upregulation on postoperative day 1 within the ipsilateral spinal cord dorsal horn, followed by a downregulation on postoperative days 3 and 5. Intraperitoneal administration of amitriptyline reversed the downregulation of EAATs in SNI rats on postoperative days 3–5 and attenuated the mechanical allodynia. We further demonstrated that administration of amitriptyline alone induced an upregulation of EAATs in sham-operated rat but do not produce an antinociceptive effect. These results indicate that amitriptyline could increase the expression of EAATs which may be one of its mechanisms in the treatment of neuropathic pain.