Experimental Neuropathy in Mice Is Associated with Delayed Behavioral Changes Related to Anxiety and Depression

Abstract

Patients with chronic pain frequently suffer affective disorders, particularly anxiety and depression. Although clinical research on the relationship between pain and depressive symptoms has been done, it is not clear whether pain causes depression or depression exaggerates pain. To investigate the relation between pain and affect, we measured anxiety and depression-related behaviors in mice after spinal nerve ligation using classical behavioral tests. After unilateral ligation of the left fifth lumbar nerve, we measured pain behaviors using von Frey and radiant heat tests. Activity level, anxiety-related behaviors, and depression-related behaviors were tested with open field, light-dark exploration, elevated plus-maze, and forced swim tests. Sensory hypersensitivity was observed within a few days after ligation. Anxiety and depression-related behaviors were not seen 2 and 7 days after ligation. However, 15 and 30 days after ligation we found clear evidence of anxiety and depression-related behaviors, without loss of mobility. Nerve injury can trigger affective disturbances in mice that appear much later than sensory hypersensitivity.