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Background and purpose Spinal cord injury (SCI) has detrimental consequences that include chronic neuropathic pain, which is seen in 40-50% of patients, and symptoms of anxiety and depression, which affect 13-45% of SCI patients. The coexistence of pain, anxiety, and depression is known from other neuropathic pain conditions, but the relationship between these symptoms is not clear and has not been investigated in a preclinical model of SCI so far. The aim of this study was to investigate anxiety-like behavior and at-level mechanical hypersensitivity following experimental spinal cord contusion (SCC) in female Sprague-Dawley rats, and the effects of analgesic and anxiolytic drugs. Methods Mechanical sensitivity and elevated plus maze (EPM) behavior were measured pre- and postinjury in SCC and sham animals. Pregabalin 30 mg/kg, morphine 3 mg/kg, midazolam 0.5 mg/kg, and 0.9% NaCl were evaluated in a randomly allocated, blinded balanced design. Results SCC animals developed persistent at-level mechanical hypersensitivity and decreased open arm activity in the EPM, which indicates an anxiety-like state. Pregabalin, a dual-acting analgesic and anxiolytic drug reduced both hypersensitivity and anxiety-like behavior, while the analgesic drug morphine only reduced hypersensitivity. The anxiolytic drug midazolam in the dose used had no effect on either parameter. Conclusions SCC animals developed long lasting coexisting at-level mechanical hypersensitivity and anxiety-like behavior, but there was no evidence to support a causal relationship between pain and anxiety following SCI. Implications The findings that at-level mechanical hypersensitivity and anxiety-like behavior develops concomitantly in the spinal cord contusion models and that both symptoms is persistent provide basis for further investigation of the mechanisms and connection behind these two clinically relevant symptoms after injury to the central nervous system.

scandinavian journal of pain

Coexisting mechanical hypersensitivity and anxiety in a rat model of spinal cord injury and the effect of pregabalin, morphine, and midazolam treatment