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Clinical studies have revealed that patients with chronic pain are more likely to have anxiety and depression, which are often associated with cognitive dysfunction. However, whether neuropathic pain can induce cognition dysfunction remains uncertain. Antidepressants and nonsteroidal anti-inflammatory drugs can treat neuropathic pain, but whether they can prevent cognition dysfunction is unknown. The present study was designed to investigate the effects and possible mechanisms of neuropathic pain on learning and memory, and the effects of amitriptyline and lornoxicam on cognitive function.Sixty male Sprague–Dawley rats were randomly subjected to L5 spinal nerve transection and sham operation, then given saline, amitriptyline and lornoxicam, respectively, during the postoperative days (7–28). Pain-related behaviours, depression-related behaviours, spatial learning and memory abilities, and expression of brain-derived neurotrophic factor were measured at different times after surgery.L5 spinal nerve transection induced mechanical allodynia and depression, and decreased the function of learning and memory as well as the expression of brain-derived neurotrophic factor. Amitriptyline ameliorated mechanical allodynia and depression-related behaviour, improved the impaired cognition, and increased the expression of brain-derived neurotrophic factor, whereas lornoxicam only inhibited the mechanical allodynia.We found that neuropathic pain may impair cognitive function via downregulation of the expression of brain-derived neurotrophic factor of the hippocampus, and amitriptyline rather than lornoxicam can ameliorate cognitive dysfunction via upregulation of brain-derived neurotrophic factor of the hippocampus.