<p>Intravenous Administration of Triptonide Attenuates CFA-Induced Pain Hypersensitivity by Inhibiting DRG AKT Signaling Pathway in Mice</p>

Abstract

Background: Currently, medical treatment of inflammatory pain is limited by a lack of safe and effective therapies. Triptonide (TPN), a major component of Tripterygium wilfordii Hook.f. with low toxicity, has been shown to have good anti-inflammatory and neuroprotective effects. The present study aims to investigate the effects of TPN on chronic inflammatory pain. Materials and Methods: Inflammatory pain was induced by intraplantar injection of complete Freund's adjuvant (CFA). TPN's three different doses were intravenously administered to compare the analgesic efficacy: 0.1 mg/kg, 0.5 mg/kg, and 2.0 mg/kg. The foot swelling was quantitated by measuring paw volume. Mechanical allodynia and thermal hyperalgesia were assessed with von Frey filament testing and Hargreaves' test, respectively. Western blots, qRT-PCR and immunofluorescence tests were used to analyze the expression of pAKT, tumor necrosis factor-α (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6). Two AKT inhibitors, AKT inhibitor Ⅳ and MK-2206, were used to examine AKT's effects on pain behavior and cytokines expression. Results: Intravenous treatment with TPN attenuated CFA-induced paw edema, mechanical allodynia, and thermal hyperalgesia. Western blotting and immunofluorescence results showed that CFA induced AKT activation in the dorsal root ganglion (DRG) neurons. However, these effects were suppressed by treatment with TPN. Furthermore, TPN treatment inhibited CFA-induced increase of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6. Consistent with the in vivo data, TPN inhibited LPS-induced Akt phosphorylation and inflammatory mediator production in ND7/23 cells. Finally, intrathecal treatment with AKT inhibitor Ⅳ or MK-2206, attenuated CFA-induced mechanical allodynia and thermal hyperalgesia, and simultaneously decreased the mRNA expression of TNF-α, IL-1β, and IL-6 in DRG. Conclusion: These data indicate that TPN attenuates CFA-induced pain potentially via inhibiting AKT-mediated pro-inflammatory cytokines production in DRG. TPN may be used for the treatment of chronic inflammatory pain.

Antioxidant Cascade Nanoenzyme Antagonize Inflammatory Pain by Modulating MAPK/p‐65 Signaling Pathway

“…Several studies have shown that CFA‐induced inflammatory pain models have significant nociceptive and inflammatory response characteristics, often used to screen new compounds for anti‐inflammatory pain activity. [ 28 ] After inducing inflammatory pain in mice using CFA, we injected SFZ NPs intrathecally and continuously monitored mechanical nociceptive hypersensitivity to evaluate its effect in treating inflammatory pain. Notably, intrathecal injection into the mouse L5 intervertebral space facilitates the direct delivery of NPs to the spinal glia.…”

VTA-NAc glutaminergic projection involves in the regulation of pain and pain-related anxiety

“…Is the pain-reducing effect of suppressing VTA-NAc glutamatergic projection sustained in acute and chronic inflammatory pain? To answer this question, the short-term and long-term CFA injection-induced pain models were prepared as acute and chronic stages of pain reported previously ( Ling et al, 2020 ). For the somatic stimulation in wild-type mice induced by the intraplantar hind paw injection of CFA, a retrograde CaMKIIa-CRE virus was injected into NAc, and DIO-EYFP-NpHR was injected with optical fiber implantation on VTA.…”

miR-506-3p Relieves Neuropathic Pain following Brachial Plexus Avulsion via Mitigating Microglial Activation through Targeting the CCL2-CCR2 Axis

“…In keeping with the approach of Ling et al [ 30 ], von Frey (vF) filaments (Stoelting, Wood Dale, IL, USA) were utilized to evaluate the mechanical threshold of the right anterior paws of all rats on day 1, 4, 7, 14, 21, and 28 following surgery. The animals were placed in a box on the elevated metal mesh floor.…”