Prearthritic treatment with etanercept reduces postarthritic macrophage accumulation in the dorsal root ganglion (DRG). (a) Inflammation due to complete Freund's adjuvant (CFA) induced a 10-fold increase in perineuronal macrophages (n = 4) by 7 days after inflammation. Infiltration of macrophages was restricted to the ipsilateral side, except for 7 days after inflammation, when a threefold increase in perineuronal macrophages was observed in the contralateral DRG. Nerve damage was assessed through double immunohistochemistry using the macrophage marker, ED1 (b) and a neuropathic marker, ATF-3 (activating transcription factor-3) (c). A maximum of two ATF-3-positive cells was detected per DRG, indicating that little nerve damage occurs in this model. (d) Prearthritic treatment with etanercept reduced macrophage numbers in the ipsilateral DRG by 75% 7 days after inflammation in comparison with controls treated with denatured etanercept (n = 4). No differences in macrophage numbers were detected with etanercept treatment commencing 3 days after inflammation induction. (e) A significant correlation between macrophage numbers in the DRG and mechanical hyperalgesia was observed 7 days after inflammation (n = 12). All treatment groups and controls were plotted. R2 = 0.667, P < 0.01. *P < 0.05,**P < 0.01, ***P < 0.005.