Role of serum interleukin-6 level on hyperalgesia and spinal mu-opioid receptor expression during the complete Freund's adjuvant-induced chronic inflammation

Interleukin (IL-6) is known to cause pro- and anti-inflammatory effects during different stages of inflammation. The purpose of this study was to elucidate the effects of IL-6 on hyperalgesia, edema and the changes in the spinal mu opioid receptor expression during different stages of complete Freund’s adjuvant (CFA)-induced arthritis (AA) in rats. In this study, AA was induced by a single subcutaneous injection of CFA into rats’ hindpaw. The rats with arthritis were divided into four groups, each consisted of three subgroups (n= 6). Anti-IL-6 was administered either daily or weekly during the 21-day study period. Spinal mu-opioid receptor (mOR) expression was detected by Western blotting. Daily treatment with an anti-IL-6 antibody significantly decreased the paw edema in the AA group compared to the control one (P=0.001), but daily and weekly anti-IL-6 administrations significantly increased the hyperalgesia in the antibody-treated group on the 14th and 21st days post-treatment (P=0.001, P=0.01, respectively). The administration of IL-6 antibody not only increased hyperalgesia in a time-dependent manner, but also caused a significant reduction in the spinal mOR expression on the 14th and 21st days post-CFA injection (P=0.01, P=0.001, respectively). Results can indicate the importance of a time-dependent relationship between the serum IL-6 level and hyperalgesia during the AA. Moreover, the results suggest that the stages of inflammation in AA must be considered for anti-hyperalgesic and anti-inflammatory interventions via anti-IL-6 antibody treatment.