Abstract # 1745 Evidence for dissociation between spontaneous pain and depression-like behavior in neuropathic pain models

Abstract

Chronic pain and depression frequently occur together but the interplay between the two is poorly understood. One of the reasons is that preclinical studies mostly focus on evoked pain hypersensitivity (allodynia and hyperalgesia) instead of spontaneous pain that is the most important component of chronic pain in humans. We used innovative approaches to study spontaneous pain in response to spared nerve injury (SNI) or chemotherapy in C57/Bl6 mice. We measured spontaneous pain by conditioned place preference (based on the ability of mice to associate relief of pain with environmental cues) and dynamic weight bearing (based on weight distribution between hindpaws in freely moving mice). We also measured depression-like behaviors in the same animals using forced swim test (FST) and sucrose preference. Our data show that retigabine, a potassium channel opener, alleviated evoked and spontaneous pain but did not block depression-like behavior induced by SNI. Conversely, genetic deletion of the tryptophan-metabolizing enzyme indoleamine 2,3-dioxygenase (IDO)1 which is required for SNI-induced depression-like behavior had no effect on evoked and spontaneous pain. Finally, treatment with cisplatin reliably induced evoked pain hypersensitivity and spontaneous pain but does not result in depression-like behavior. Taken together our data indicate that chronic pain per se is not sufficient to cause depression-like behavior in models of neuropathic pain and conversely that depression-like behavior does not modulate the pain response.