162. Comorbid chronic pain and depression: A search for common neuroimmune mechanisms

Abstract

In humans, chronic neuropathic pain is a risk factor for depression, but the mechanisms underlying this association remain elusive. Spared nerve injury (SNI) is a rodent model of chronic neuropathic pain that is associated with depressive-like behavior in most studies. Central nervous system microglial activation and pro-inflammatory cytokine production contribute to both chronic neuropathic pain and depressive-like after SNI. We have recently established that depressive-like behavior induced by peripheral inflammation requires the activation of IDO-1, a tryptophan metabolizing enzyme. Here we determined the contribution of IDO-1 to SNI-induced neuropathic pain and depressive-like behavior. SNI or sham surgery was performed in wild type and IDO-1-KO mice. As expected, SNI induced the development of mechanical hyperalgesia as well as depressive-like behavior (reduced sucrose preference and increased immobility in the forced swim test), without affecting locomotor activity in a novel cage. In accordance with results from others, SNI increased brain pro-inflammatory cytokine production. IDO-1-KO mice developed mechanical hyperalgesia with similar kinetics and severity as WT mice. However, IDO-1 KO mice did not develop depressive-like behavior. In conclusion, IDO-1 is a critical enzyme required for development of depressive-like behavior in the context of neuropathic pain after SNI. The involvement of IDO-1 in depression is specific since its absence does not modify the pain response after SNI. Funded by NIH R01-NS073939 (A.K., R.D., K.W.K.); RO1-NS074999 (A.K.); R01-MH079829 (R.D.), R01-AG-029573 (K.W.K.).