Specialized pro-resolving mediator Maresin 1 attenuates pain in a mouse model of osteoarthritis.

Objective: We test whether the specialized pro-resolving molecule Maresin 1 (MaR1) attenuates nociceptive behaviors in mice with osteoarthritis-like pain.

Design: Osteoarthritis (OA)-like pain behavior was induced by intra-articular injection of monosodium iodoacetate (MIA) and treated with MaR1 (N=6) or vehicle (N=5) by intraperitoneal injection 8 weeks after injury. Mice without MIA injection were used as control (N=6). Nociceptive behaviors were examined by von Frey and dynamic weight bearing measurements. Calcitonin gene-related peptide (CGRP) expression and activated macrophages in the dorsal root ganglion (DRG) were examined by immunofluorescence staining. The inflammatory profile in circulation was assessed by cytokine array. Calcium imaging was performed to assess the in vitro functional response of DRG neurons from animals with OA-like pain behavior to MaR1 with or without RAR Related Orphan Receptor A (RORA) inverse agonist SR3335.

Results: MaR1 attenuated knee pain behavior in treated mice (N=6) compared to non-treated mice (N=5) as shown by increased paw withdrawal threshold with a mean difference of 112.2% (95% CI [49.79, 174.6], p=0.0784) at 4 h and 150.9% (95% CI [104.2, 197.5], p=0.0001) at 4 days post-MaR1 treatment, and increased weight bearing with a mean difference of 20.08% (95% CI [2.798, 37.37], p=0.0277) at 1 day post-MaR1 treatment. CGRP expression and activated macrophages were decreased in the DRG, and inflammatory cytokine levels in the circulation were attenuated. Calcium imaging showed MaR1 reduced the functional response of DRG neurons through RORA.

Conclusions: Our results show that MaR1 reduces OA-like pain behavior in mice and could be a potential treatment for OA pain.