Enhancing Burn Pain Management: The Therapeutic Potential of Cocoa Extract as a Tramadol Adjuvant in Modulating MCP-1 and Glutamate in Animal Model

Abstract

Burn wound pain management remains a significant clinical challenge, with up to 80% of patients experiencing severe pain. This pain results from complex interactions between nociceptive stimuli and inflammatory cascades that can progress to chronic pain states. While multimodal analgesia combining NSAIDs and opioids is standard practice, novel adjuvants are needed to optimize pain control. Cocoa contains bioactive flavonoids with documented anti-inflammatory, antioxidant, and analgesic properties, including inhibition of key inflammatory mediators (IL-1β, TNF-α, MCP-1). This study investigated cocoa extract as a potential adjuvant to tramadol for burn pain management. In this randomized controlled experimental study, 15 male Wistar rats were equally divided into three groups: control (placebo), tramadol-ibuprofen combination (12.5 mg/kg and 15 mg/kg, respectively), and tramadol-cocoa combination (12.5 mg/kg and 0.5 g/kg, respectively). Second-degree burns were induced by immersing the right hind paw in 65°C water for 3 seconds. Pain sensitivity was assessed using Von Frey filaments at 24 hours post-injury. Plasma MCP-1 and tissue glutamate levels were quantified using ELISA. Von Frey testing revealed significant analgesic effects in both treatment groups compared to control (p=0.003), with the tramadol-cocoa combination (p=0.005) demonstrating comparable efficacy to tramadol-ibuprofen (p=0.010). No significant difference was observed between treatment groups (p=0.930). While MCP-1 levels showed no significant variation across groups (p=0.063), tissue glutamate concentrations were significantly reduced in both tramadol-ibuprofen (p=0.017) and tramadol-cocoa groups (p=0.046) compared to control, with no significant difference between treatments (p=0.069). Cocoa extract demonstrates promising potential as an analgesic adjuvant, achieving pain reduction comparable to standard tramadol-ibuprofen therapy. The significant reduction in tissue glutamate levels suggests a potential mechanism through modulation of excitatory neurotransmission. These findings support further investigation of cocoa-based adjuvants as a novel, natural approach to multimodal burn pain management.