Abstract
BackgroundRubus occidentalis, also known as black raspberry, contains several bioactive components that vary depending on the maturity of the fruit. The goal of this study was to evaluate the efficacy of immature Rubus occidentalis extract(iROE) on acid-induced hyperalgesia, investigate the mechanism involved, and compare the antihyperalgesic effect of immature and mature ROEs.MethodsIn adult male Sprague-Dawley rats, chronic muscle pain was induced via two injections of acidic saline into one gastrocnemius muscle. To evaluate the dose response, the rats were injected intraperitoneally with 0.9% saline or iROE (10, 30, 100, or 300 mg/kg) following hyperalgesia development. To evaluate the mechanism underlying iROE-induced analgesia, the rats were injected intraperitoneally with saline, yohimbine 2 mg/kg, dexmedetomidine 50 μg/kg, prazosin 1 mg/kg, atropine 5 mg/kg, mecamylamine 1 mg/kg, or naloxone 5 mg/kg 24 h after hyperalgesia development, followed by iROE 300 mg/kg administration. To compare immature versus mature ROE, the rats were injected with mature ROE 300 mg/kg and immature ROE 300 mg/kg after hyperalgesia development. For all experiments, the mechanical withdrawal threshold(MWT) was evaluated using von Frey filaments before the first acidic saline injection, 24 h after the second injection, and at various time points after drug administration. Data were analysed using multivariate analysis of variance(MANOVA) and the linear mixed-effects model(LMEM). We compared the MWT at each time point using analysis of variance with the Bonferroni correction.ResultsThe iROE 300 mg/kg injection resulted in a significant increase in MWT compared with the control, iROE 30 mg/kg, and iROE 100 mg/kg injections at ipsilateral and contralateral sites. The iROE injection together with yohimbine, mecamylamine, or naloxone significantly decreased the MWT compared with iROE alone, whereas ROE together with dexmedetomidine significantly increased the MWT. According to MANOVA, the effects of immature and mature ROEs were not significantly different; however, the LMEM presented a significant difference between the two groups.ConclusionsImmature R. occidentalis showed antihyperalgesic activity against acid-induced chronic muscle pain, which may be mediated by the α2-adrenergic, nicotinic cholinergic, and opioid receptors. The iROE displayed superior tendency regarding analgesic effect compared to mature ROE.
Highlights
Rubus occidentalis, known as black raspberry, contains several bioactive components that vary depending on the maturity of the fruit
To identify the relationship between chronic musculoskeletal pain and immature R. occidentalis, we developed a rat model with hyperalgesia induced by repeated intramuscular injection of acidic saline; immature R. occidentalis extract was administered intraperitoneally
The mechanical withdrawal threshold (MWT) in the immature R. occidentalis extract (iROE) 10 mg/kg, iROE 30 mg/kg, iROE 100 mg/kg, and iROE 300 mg/kg groups was significantly higher than that in the control group at the ipsilateral (MD 0.15; 95% CI 0.05 to 0.25; P = 0.030, Mean difference (MD) 0.23; 95% CI 0.13 to 0.33; P < 0.001, MD 0.40; 95% CI 0.30 to 0.50; P < 0.001, MD 0.54; 95% CI 0.44 to 0.64; P < 0.001, respectively) and contralateral sites
Summary
Known as black raspberry, contains several bioactive components that vary depending on the maturity of the fruit. The goal of this study was to evaluate the efficacy of immature Rubus occidentalis extract(iROE) on acid-induced hyperalgesia, investigate the mechanism involved, and compare the antihyperalgesic effect of immature and mature ROEs. Chronic musculoskeletal pain has a considerable influence on physical, emotional, psychological, and social aspects with only few effective therapeutic strategies. Multimodal therapeutic approaches using various medications and techniques are recommended for chronic pain control; this condition remains difficult to treat. The pharmacological regimen for pain management tends to emphasise opioid sparing. Pharmacological strategies for pain control should be safe to enable their use over a long duration. In this regard, recently, there is a growing interest in therapeutic approaches based on food for the management of chronic pain. Several investigations have suggested the health benefits of functional foods or nutraceuticals and their potential for relieving chronic pain [2]
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