Depression-like behavior and mechanical allodynia are reduced by bis selenide treatment in mice with chronic constriction injury: a comparison with fluoxetine, amitriptyline, and bupropion

Abstract

Rationale: Neuropathic pain is associated with significant co-morbidities, including depression, which impact considerably on the overall patient experience. Pain co-morbidity symptoms are rarely assessed in animal models of neuropathic pain. Neuropathic pain is characterized by hyperexcitability within nociceptive pathways and remains difficult to treat with standard analgesics.

Objectives: The present study determined the effect of bis selenide and conventional antidepressants (fluoxetine, amitriptyline, and bupropion) on neuropathic pain using mechanical allodynic and on depressive-like behavior.

Methods: Male mice were subjected to chronic constriction injury (CCI) or sham surgery and were assessed on day 14 after operation. Mice received oral treatment with bis selenide (1-5 mg/kg), fluoxetine, amitriptyline, or bupropion (10-30 mg/kg). The response frequency to mechanical allodynia in mice was measured with von Frey hairs. Mice were evaluated in the forced swimming test (FST) test for depression-like behavior.

Results: The CCI procedure produced mechanical allodynia and increased depressive-like behavior in the FST. All of the drugs produced antiallodynic effects in CCI mice and produced antidepressant effects in control mice without altering locomotor activity. In CCI animals, however, only the amitriptyline and bis selenide treatments significantly reduced immobility in the FST.

Conclusion: These data demonstrate an important dissociation between the antiallodynic and antidepressant effects in mice when tested in a model of neuropathic pain. Depressive behavior in CCI mice was reversed by bis selenide and amitriptyline but not by the conventional antidepressants fluoxetine and buproprion. Bis selenide was more potent than the other drugs tested for antidepressant-like and antiallodynic effects in mice.