Sinomenine is a principal ingredient of traditional Chinese medicine, Sinomenium Acutum, which has been reported to have various pharmacological effects including anti-rheumatism and immunomodulation. This study examined the effects of sinomenine in rats that received chronic constriction injury (CCI), a model of peripheral neuropathic pain. CCI injury on the right sciatic nerve led to long-lasting mechanical hyperalgesia. Acute sinomenine treatment (10–40 mg/kg, i.p.) significantly and dose-dependently reversed mechanical hyperalgesia. In addition, the antinociceptive effects of sinomenine remained stable during repeated daily treatment for up to 2 weeks. Although sinomenine did not alter the duration of immobility in the forced swimming test in healthy animals, it dose-dependently reversed the increased immobility time in rats receiving CCI, suggesting that sinomenine attenuated chronic pain-induced depressive-like behavior. The antinociceptive effects of sinomenine were blocked by the GABAa receptor antagonist bicuculine. The doses of sinomenine studied here did not significantly alter the spontaneous locomotor activity. Together, these results suggested that sinomenine exerts significant antinociceptive effects for neuropathic pain via GABAa-mediated mechanism, which suggests that sinomenine may be useful for the management of chronic painful conditions such as neuropathic pain.

Vitexin, a C-glycosylated flavone present in several medicinal herbs, has showed various pharmacological activities including antinociception. The present study investigated the antinociceptive effects of vitexin in a mouse model of postoperative pain. This model was prepared by making a surgical incision on the right hindpaw and von Frey filament test was used to assess mechanical hyperalgesia. Isobolographical analysis method was used to examine the interaction between vitexin and acetaminophen. A reliable mechanical hyperalgesia was observed at 2 h post-surgery and lasted for 4 days. Acute vitexin administration (3–10 mg/kg, i.p.) dose-dependently relieved this hyperalgesia, which was also observed from 1 to 3 days post-surgery during repeated daily treatment. However, repeated vitexin administration prior to surgery had no preventive value. The 10 mg/kg vitexin-induced antinociception was blocked by the opioid receptor antagonist naltrexone or the GABA_Areceptor antagonist bicuculline. The doses of vitexin used did not significantly suppress the locomotor activity. In addition, the combination of vitexin and acetaminophen produced an infra-additive effect in postoperative pain. Together, though vitexin-acetaminophen combination may not be useful for treating postoperative pain, vitexin exerts behaviorally-specific antinociception against postoperative pain mediated through opioid receptors and GABA_Areceptors, suggesting that vitexin may be useful for the control of postoperative pain.

Curcumin is a principal ingredient of traditional Chinese medicine, Curcuma Longa, which possesses a variety of pharmacological activities including pain relief. Preclinical studies have demonstrated that curcumin has antinociceptive effects for inflammatory and neuropathic pain. This study examined the effects of curcumin in a rat model of postoperative pain. A surgical incision on the right hind paw induced a sustained mechanical hyperalgesia that lasted for 5 days. Acute curcumin treatment (10–40 mg/kg, p.o) significantly and dose dependently reversed mechanical hyperalgesia. In addition, repeated curcumin treatment significantly facilitated the recovery from surgery. In contrast, repeated treatment with curcumin before surgery did not impact the postoperative pain threshold and recovery rate. All the doses of curcumin did not significantly alter the spontaneous locomotor activity. Combined, these results suggested that curcumin could alleviate postoperative pain and promote recovery from the surgery, although there was no significant preventive value. This study extends previous findings and supports the application of curcumin alone or as an adjunct therapy for the management of peri-operative pain.

Advanced breast cancer with recurrent and distal organ metastasis is aggressive and incurable. The current existing treatment strategies for advanced breast cancer are difficult to achieve synergistic treatment of recurrent tumors and distant metastasis, resulting in poor clinical outcomes. Herein, a synergistic therapy strategy composed of biomimetic tumor‐derived exosomes (TEX)‐Liposome‐paclitaxel (PTX) with lung homing properties and gold nanorods (GNR)‐PEG, was designed, respectively. GNR‐PEG, with well biocompatibility, cured recurrent tumors effectively by thermal ablation under the in situ NIR irradiation. Meanwhile, GNR‐mediated thermal ablation activated the adaptive antitumor immune response, significantly increased the level of CD8⁺ T cells in lungs and the concentration of serum cytokines (tumor necrosis factor‐α, interlekin‐6, and interferon‐γ). Subsequently, TEX‐Liposome‐PTX preferentially accumulated in lung tissues due to autologous tumor‐derived TEX with inherent specific affinity to lung, resulting in a better therapeutic effect on lung metastasis tumors with the assistance of adaptive immunotherapy triggered by GNR in vivo. The enhanced therapeutic efficacy in advanced breast cancer was a combination of thermal ablation, adaptive antitumor immunotherapy, and targeted PTX chemotherapy. Hence, the synergistic strategy based on GNR and TEX‐Liposome provides selectivity to clinical treatment of advanced breast cancer with recurrent and metastasis.