Differences in Depressive‐ and Anxiety‐like effects in S426A/S430A Mutant and Wild‐type Mice Following the Induction of Neuropathic Pain

Abstract

Clinically, chronic pain has been associated with increases in anxiety‐ and depressive‐like symptoms, concomitant with the severity and duration of pain. Pursuant to the on‐going opioid crisis, novel therapeutic approaches, including the use of cannabinoids, have been investigated for the management of chronic pain. We have previously demonstrated that mice expressing a desensitization form of the cannabinoid type‐1 (CB1) receptor (S426A/S430A) show delayed tolerance and heightened sensitivity to the anti‐nociceptive effects of Δ9‐tetrahydrocannabinol (Δ9‐THC). In addition to analgesia, cannabinoids have been implicated in mediating affect in select mood disorders. Therefore, the purpose of the present study was to examine whether the induction of chronic neuropathic pain would alter anxiety and/or depressive‐like phenotypes in either wild‐type and/or S426A/S430A mutant mice, and whether the severity of these symptoms correlated with either basal allodynia or Δ9‐THC‐induced anti‐allodynic responses. Male and female wild‐type and S426A/S430A mice were assessed for alterations in locomotor behavior, anxiety‐like (elevated plus maze; open field) and depressive‐like (forced swim test) behaviors before and after the induction of cisplatin‐evoked neuropathic pain. Mice were also assessed to see whether basal pain levels correlated with either anxiety‐ and/or depressive‐like behaviors, and whether increased anxiety‐ and/or depressive‐like symptoms correlated with the degree of anti‐allodynia produced following pretreatment with Δ9‐THC. All mice showed evidence of neuropathic pain following repeated cisplatin‐treatment. Interestingly, the S426A/S430A mutation caused female (but not male) mice to exhibit reduced anxiety‐like behavior prior to the induction of cisplatin pain but caused them to be more susceptible to anxiety and depressive‐like symptoms once they exhibited cisplatin‐evoked pain. Pretreatment with Δ9‐THC was also able to completely reverse allodynia in male and female mutant, but not wild‐type, mice. Taken together, these results highlight the importance of understanding the role that sex may have in the potential clinical use of cannabinoids to modulate both affective and sensory aspects of chronic pain.Support or Funding InformationPenn State University College of Medicine Department of Anesthesiology & Perioperative MedicineThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.