Neuropathic pain caused by nerve injury presents with severe spontaneous pain and a range of comorbidities, including deficits in higher executive functioning, none of which are adequately treated with current analgesics. Interleukin-6 (IL-6), a proinflammatory cytokine, is critically involved in the development and maintenance of central sensitization. However, the roles of IL-6 in neuropathic pain and related comorbidities have yet to be fully clarified. The present study examined the effect of MR16-1, an anti-IL-6 receptor antibody and inhibits IL-6 activity, on allodynia and cognitive impairment in mice with neuropathic pain following partial sciatic nerve ligation (PSNL). Significant upregulation of IL-6 expression was observed in the hippocampus in PSNL mice. Intranasal administration of MR16-1 significantly improved cognitive impairment but not allodynia in PSNL mice. Intranasal MR16-1 blocked PSNL-induced degenerative effects on hippocampal neurons. Intraperitoneal administration of MR16-1 suppressed allodynia but not cognitive impairment of PSNL mice. The findings suggest that cognitive impairment associated with neuropathic pain is mediated through changes in hippocampus induced by IL-6. These data also suggest that IL-6 mediated peripheral inflammation underlies allodynia, and IL-6 mediated inflammation in the central nervous system underlies cognitive impairment associated with neuropathic pain, and further suggest the therapeutic potential of blocking IL-6 functioning by blocking its receptor.