Anti-nociceptive effects of magnolol via inhibition of TRPV1/P2Y and TLR4/NF-κB signaling in a postoperative pain model

The current study explored the anti-nociceptive activity of magnolol in post-incisional inflammatory nociceptive pain. Preliminary, the anti-inflammatory, antioxidant, and cytoprotective potential of magnolol were confirmed against hydrogen peroxide (H2O2)-induced PC12 cells. Next, an in-vivo model of planter incision surgery was established in BALB/c mice. Tramadol 50 mg/kg intraperitoneal (i.p.) and magnolol (0.1, 1, 10 mg/kg i.p. + 10 mg/kg intra planter) were administered after plantar incision surgery and behavior parameters were measured. The results indicate that magnolol significantly suppressed post-incision-induced mechanical allodynia, thermal hyperalgesia, and paw edema. Magnolol promisingly inhibited post-incision induces nitric oxide (NO), malondialdehyde (MDA), eosinophil peroxidase (EPO), and neutrophil infiltration. Magnolol strongly attenuated post-incision inducing the release of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and inhibited deoxyribonucleic acid (DNA) fragmentation. Magnolol markedly reverses post-incisional histopathological changes and biochemical composition of the incised paw. Magnolol markedly down-regulated post-incisional increase expression of transient receptor potential vanilloid 1 (TRPV1), purinergic (P2Y) nociceptors as well as toll-like receptor 4 (TLR4), nuclear factor kappa light chain enhancer of activated B cell (NF-κB), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) while upregulating the expression of inhibitor of nuclear kappa B alpha (IκB-α). The present study strongly suggests that magnolol significantly suppressed post-incisional inflammatory nociceptive pain by targeting TRPV1/P2Y and TLR4/NF-κB signaling.