The analgesic effect of curcumin and nano-curcumin in clinical and preclinical studies: a systematic review and meta-analysis

Chronic pain remains a treatment challenge. Curcumin, a natural plant product found in the Curcuma genus, has been shown to possess anti-inflammatory, antioxidant, and neuroprotective properties. In this systematic review and meta-analysis, we aimed to evaluate the efficacy of curcumin and nano-curcumin for treating chronic pain in clinical and preclinical studies. A systematic search was performed through PubMed, SCOPUS, Web of Science Core Collection, Cochrane, and Google Scholar up to April 1, 2023, using relevant keywords. Trials that met the inclusion criteria were included in this study. We applied the mean difference (MD) or standardized mean difference (SMD) in random or fixed-effects models to analyze the impact of combined trials. We also evaluated the potential risk of bias using the Higgins method for clinical studies and the SYRCLE Risk of Bias tool for animal studies. Our meta-analysis included 59 studies, comprising 29 animal studies and 30 clinical studies. Curcumin strongly reduced pain in preclinical studies, and both the intraperitoneal (SMD = 1.48; 95% CI, 0.81 to 2.14; p < 0.001, and I-2 = 77.9%) and oral (SMD = 1.27; 95% CI, 1.01 to 1.55; p < 0.001, and I-2 = 0.0%) administration method of curcumin had pain-relieving effects. However, the subcutaneous method (SMD = 0.24; 95% CI, - 0.89 to 1.38; p = 0.67) had no effect. The drug's efficacy within the 100-250 mg range (SMD = 1.46; 95% CI, 0.76 to 2.15; p < 0.001; and I-2 = 73.4%) surpassed that observed above 250 mg (SMD = 1.23; 95% CI, 0.89 to 1.57; p < 0.001; and I-2 = 0.0%). In clinical studies, nano-curcumin had a powerful effect on pain reduction compared to placebo (MD = - 1.197; CI 95% (- 1.94 to - 0.45); p = 0.002; and I-2 = 80.9%), and the effects of NSAIDs on pain were not significantly altered when used in combination with Curcuma longa extract (MD = - 0.23; CI 95% (- 0.99 to 0.53); p = 0.554; and I-2 = 92%). In addition, the effect of increased bioavailability of curcumin (MD = - 1.54; CI 95% (- 2.06 to - 1.02); p < 0.001; and I-2 = 89.6%), curcumin (MD = - 1.35; CI 95% (- 2.451 to - 0.252); p = 0.016; and I-2 = 90.8%), and nano-curcumin was greater than placebo. Our meta-analysis suggests that curcumin and nano-curcumin are effective in reducing chronic pain. These findings have important implications for pharmaceutical science and may lead to the development of new treatments for chronic pain. However, further research is needed to confirm these findings.