Background Rheumatoid arthritis (RA) is a chronic, autoimmune inflammatory disease that affects approximately 1% of the population. The early stages of RA are characterized by activation of innate immunity including activation of macrophages (1). Activated macrophages, either resident or recruited from the blood vessels, may release widespread inflammatory mediators that can critically contribute to acute and chronic disease (2).
Objectives The aim of our present study was to compare a distribution of activated macrophages in the lumbar dorsal root ganglia (DRGs) and their number changes in time of survival. In addition, we monitored manifestation of neuropathic pain using behavioral test.
Methods For induction of unilateral antigen-induced arthritis (AIA), rats (n=42) were immunized by an intra-articular injection of Complete Freund's Adjuvant (CFA, 50 μl) into the right knee joint. The knee joints of control rats were injected with 50 μl of sterile saline. Naïve rats were without AIA induction and injection of saline. All experimental animals were left to survive for 1, 2, 4, 7, 14 and 21 days. Activated macrophages were detected by ED1 immunostaining and quantified bilaterally in the lumbar DRGs (L3 and L5) using image analysis system (NIS Elements). Neuropathic pain expressed by mechanical allodynia was measured using the dynamic plantar esthesiometer. The data differences were evaluated by Mann-Whitney test using STATISTICA software.
Results Activated macrophages were found bilaterally. On the ipsilateral side, we observed robust increase of activated macrophages during the first four days and 21 days after CFA application. However, 7 and 14 days after was decreased number of activated macrophages. Contralateral ganglia displayed increased number of ED1+ macrophages during the first two days, followed by a decline at 14 day after immunization with subsequent increase. A greater increase of activated macrophage was observed in L3 than L5 DRG that could be related to the afferent innervation of the ventral and dorsal side of knee joint capsule, respectively.
Mechanical allodynia indicating neuropathic pain in the ipsilateral hind paws was decreased from 1 day to 14 days after RA induction. Contralateral hind paws displayed also statistically significant changes of withdrawal thresholds for mechanical allodynia from 7 to 14 days after RA induction.
Conclusions Dynamic of macrophage activation was observed bilaterally in L3 and L5 DRGs of rats subjected by unilateral AIA from 1 to 21 days. The results of macrophage activation in L3 and L5 DRGs are related with afferent innervation of the knee joint.
Segond von Banchet, Gisela, et al. Experimental arthritis causes tumor necrosis factor-α-dependent infiltration of macrophages into rat dorsal root ganglia which correlates with pain-related behavior. Pain, 2009, 145.1: 151-159.
Kinne, Raimund W., et al. Macrophages in rheumatoid arthritis. Arthritis research, 2000, 2.3: 189-202.
Acknowledgements Supported by the project CEITEC (CZ.1.05/1.1.00/02.0068) from European Regional Development Fund.
Disclosure of Interest None declared