Morphine-induced persistent sensitization is mediated by central immune signaling. (A) IL-1ra (blue hatch; 5 d) was coadministered with morphine (5 d; shaded area), 10 d after CCI surgery, and absolute thresholds for mechanical allodynia were quantified in F344 rats. Morphine (5 d; shaded area) was administered 10 d after CCI surgery, (b) IL-1ra, (c) etanercept or TB-2–081 were intrathecally administered 5 wk after morphine conclusion, and absolute thresholds for mechanical allodynia quantified in F344 rats. Ipsilateral lumbar dorsal spinal cords were collected from CCI/sham F344 rats, 5 wk after morphine/saline administration and phospho-NR1 (D), GRK2 (E), and GLT-1 (F) protein levels were quantified. *P < 0.05; **P < 0.01; ***P < 0.001 [relative to vehicle (A–C) and relative to sham+saline (D–F)]; #P < 0.05; ###P < 0.001 [TB-2-081 vs. vehicle (C) and relative to sham+morphine (D–F); ^^P < 0.01; ^^^P < 0.001 [relative to CCI+saline[ (D–F)] . Data are presented as mean ± SEM; n = 5–7 per group.