Efficacy, Safety, and Impact of Combined Extended-Release Tramadol Hydrochloride and Acetaminophen on Inflammatory Mediators in Malignant Lymphoma-Associated Pain
Xiaohua Qi, Li Zhu, Jianzhen Li, Yan LiBackground:
Malignant lymphoma-associated pain significantly impairs quality of life and is linked to systemic inflammatory responses. This study evaluated the efficacy and safety of combining extended-release tramadol hydrochloride with acetaminophen compared with monotherapy.
Objective:
This study aimed to evaluate the efficacy and safety of tramadol hydrochloride extended-release tablets in combination with acetaminophen versus monotherapy with either agent in the treatment of malignant lymphoma-related pain, and to investigate the effects of these treatment regimens on peripheral pain mediators and systemic inflammatory cytokines.
Methods:
A comparative study was conducted involving 165 patients with malignant lymphoma-associated pain (January 2024-December 2025). Patients were assigned to 3 groups: acetaminophen (n = 53), tramadol (n = 55), or combination therapy (n = 57), receiving 28 days of treatment. Primary outcomes included Numerical Rating Scale (NRS) pain scores and analgesic efficacy. Secondary outcomes included peripheral blood pain mediators (substance P [SP], prostaglandin E2 [PGE2], endothelin-1 [ET-1], 5-hydroxytryptamine [5-HT]), inflammatory cytokines (interleukin [IL]-2, IL-4, IL-6, IL-10, tumor necrosis factor-
Results:
The combination group demonstrated significantly greater reductions in NRS scores and superior analgesic efficacy (91.23%) compared with acetaminophen (71.70%) and tramadol (78.18%) groups
Conclusion and Relevance:
The combination of tramadol hydrochloride extended-release tablets and acetaminophen provides superior analgesic efficacy and greater improvement in quality of life compared with either monotherapy in the treatment of malignant lymphoma-related pain, and its mechanism is associated with the synergistic downregulation of peripheral pain mediators and modulation of the inflammatory cytokine profile. During the treatment period, the combination regimen did not significantly increase the risk of adverse reactions, demonstrating a favorable benefit-risk ratio. This report is the first to simultaneously confirm, in this patient population, both the clinical efficacy of this combination regimen and its modulatory effects on the systemic pain-inflammation network, thereby providing a strategy for enhanced analgesia in clinical practice. Based on the data from this study, this regimen may serve as an effective option for the short-term management of moderate to severe pain in patients with malignant lymphoma; however, its long-term efficacy and broad applicability require further investigation.