Altogether, our findings reveal a role for NOV in the modulation of CFA-induced pain by exerting antiinflammatory and anti-allodynic effects. Our study provides for the first time evidence that, besides their recently demonstrated roles in the pathogenesis of neuropathic pain, MMP-2/-9 could be involved in chronic inflammatory pain as well. We hypothesize that, during chronic inflammation, NOV downregulation in DRG and spinal cord contributes to MMP-2/-9 induction thereby participating in the maintenance of pain intensity. Because NOV appears as a novel mediator in the functional interplay between cytokine and MMPs in pain processes, it may alone or in concert with other drugs represent a new interesting analgesic. Knowing that recent evidence renders MMP-2/-9 useful targets for neuropathic pain relief [56], the investigation of NOV involvement in neuropathic pain would be worthwhile research, and preliminary **data** from our laboratory in this matter appear promising. Nevertheless further comprehensive research is needed to investigate the precise mechanisms involved in such function in order to improve therapeutic solutions.