Activation of
mitogen-activated protein kinase (MAPK)
enzymes in nociceptive plasticity has been extensively studied.
P38 MAPK enzyme, which can be activated by
cytokines, acts as a crucial intracellular regulator of environmental changes. The aim of this study was to elucidate the cellular events during
arthritis-induced
hyperalgesia that are mediated by
interleukin-6 and
p38 MAPK, and their effects on the expression of spinal
mu-opioid receptors (MORs), in different stages of
arthritis in male Wistar rats. Complete
Freund's adjuvant (CFA)-induced
arthritis (AA) was caused by
subcutaneous injection of CFA into the rats' hindpaw. Anti-IL-6 antibody and
p38 MAPK phosphorylation inhibitor were administered during 21 days of study. Spinal MOR, p38, and phosphorylated-p38 (pp38)
proteins expressions were detected by Western blotting. Daily treatment with anti-IL-6 antibody and
p38 MAPK phosphorylation inhibitor,
SB203580, significantly decreased paw
edema in AA group. Daily anti-IL-6 and
SB203580 administration caused a significant reduction in
hyperalgesia in the first week of the study, but increased
hyperalgesia in the next 2 weeks in experimental groups compared to the AA control group. Expression of pp38 MAPK
protein significantly decreased on the 3, 7, 14, and 21 days in AA+SB203580 and AA+anti-
IL6 groups compared to AA group. Additionally, daily treatment with anti-IL6 antibody and
SB203580 in AA group caused significantly decrease in spinal MOR expression compared to AA control group. The results of our study can confirm that activated spinal
p38 MAPK enzyme may play an important role in cellular
IL-6 signaling pathways in
hyperalgesia variation during different stages of AA
inflammation. Also, it can be suggested that at least a part of
p38 MAPK effects on
hyperalgesia is mediated by spinal MOR expression variation.