RESEARCH ARTICLE Relationship between serum IL10 level and p38MAPK enzyme activity on behavioral and cellular aspects of variation of hyperalgesia during different stages of arthritis in rats Jalal Zaringhalam • Zeinab Akhtari • Akram Eidi • Ali Haeri Ruhani • Elaheh Tekieh Received: 28 April 2013 / Accepted: 17 May 2013 / Published online: 14 June 2013 Ó Springer Basel 2013 Abstract Objects and design Regarding to anti-inflammatory role of interleukin (IL) 10, its inhibitory effects on p38MAPK activity and, different pro and anti-inflammatory roles of activated p38MAPK in cells, this study was aimed to investigate relationship between serum IL10 level and p38MAPK enzyme activity on behavioral and cellular aspects variation of hyperalgesia during different stages of arthritis in rats. Materials and methods Adjuvant arthritis (AA) was induced by a single subcutaneous injection of complete Freund’s adjuvant into the rats’ hind paw. Behavioral and inflammatory responses were assessed at 0, 3, 7, 14, and 21 days of study. Receptor and other protein enzyme expression variations were detected by western blotting. Anti-IL10 and p38MAPK inhibitor were administered daily during the 21 days of study. Result Daily treatment with anti-IL10 antibody signifi- cantly increased paw edema and hyperalgesia in the AA group compared with the AA control group. Administra- tion of anti-IL10 antibody caused significant increase in the ratio of phosphorylated p38 to p38MAPK enzyme level expression on 14th and 21st days of study compared with the AA control group. Conclusion Our study confirmed that a part of anti- inflammatory effects of serum IL10 during AA inflamma- tion was mediated via inhibition of p38MAPK enzyme phosphorylation. Moreover, these findings suggest that increase in the level of spinal mu opioid receptor expres- sion during AA inflammation is not mediated via the direct effect of serum IL10 on spinal p38MAPK. Keywords IL10 Á Arthritis Á Hyperalgesia Á Mu opioid receptor Á p38MAPK Introduction Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation of the synovium, with symptoms that include joint pain, edema, and stiffness (Scott et al. 2010). Complete Freund’s adjuvant (CFA)- induced arthritis (AA) in rats is an inflammatory model widely used in etiopathogenic investigational drug and molecular studies due to its similarity to human RA. Our previous study revealed that CFA-induced hyperalgesia on the 7th day after injection was correlated with increases in inflammatory mediators, such as interleukin-6 (IL6) and tumor necrosis factor a (TNFa). However, hyperalgesia significantly reduced on 14th and 21st days after AA induction (next 2 weeks) (Tekieh et al. 2011). Some studies indicated that inflammation progresses by the action of pro-inflammatory cytokines, including interleu- kin-1 (IL1), TNFa, gamma-interferon (IFNc), interleukin- 12 (IL12), interleukin-18 (IL-18), and the granulocyte– macrophage colony-stimulating factor, and is resolved by anti-inflammatory cytokines such as interleukin-4 (IL4), J. Zaringhalam (&) Physiology Department, Shahid Beheshti University of Medical Sciences, Tehran, Iran e-mail: jzaringhalam@yahoo.com J. Zaringhalam Á E. Tekieh Neuroscience Research Centre, Shahid Beheshti University of Medical Sciences, Tehran, Iran Z. Akhtari Á A. Eidi Á A. H. Ruhani Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran Inflammopharmacol (2014) 22:37–44 DOI 10.1007/s10787-013-0174-8 Inflammopharmacology 123