Evaluation Of The Analgesic Effect Of The Combination Of Pregabalin,Duloxetine And Non-Steroidal Anti-Inflammatory Drugs

Pain is a condition that can cause disability,decreased quality of life and reduced workforce for patients.The main common analgesic drugs recommended are NSAIDs,antiepileptics,antidepressants and opioids.However,the existing analgesic drugs suffer from limited drug selection,lower than expected analgesic effect or high risk of adverse effects when used singly.Therefore,current pain treatment needs cannot be adequately met,and adequate pain treatment remains a challenging clinical challenge.Neuropathic pain is often closely associated with nerve injury or inflammation,and the role of traditional non-steroidal anti-inflammatory drugs as adjuvants for treating chemotherapy-induced peripheral neuropathic pain remains unclear.In this thesis study,the potential synergistic antinociceptive effects of indomethacin/meloxicam-pregabalin,and indomethacin/meloxicam-duloxetine in neuropathic pain and inflammatory pain were investigated by paclitaxel-induced neuropathic pain and carrageenan-induced inflammatory pain models.Indomethacin and meloxicam alone alleviated mechanical nociceptive hyperalgesia induced by the two models mentioned above,but isobolographic analysis showed that the combination of indomethacin or meloxicam with pregabalin and duloxetine produced significant synergistic antinociceptive effects for paclitaxel-induced neuropathic pain(The experimental ED₂₅ was less than the theoretical ED₂₅,indicating a synergistic analgesic effect between the two drugs.Indomethacin-Pregabalin（IN-PGB）,experimental ED₂₅(ED₂₅E)=4.41 mg/kg,theoretical ED₂₅(ED₂₅T)=8.50 mg/kg;Meloxicam-Pregabalin（MEL-PGB）,ED₂₅E=3.96 mg/kg,ED₂₅T=7.52 mg/kg;Indomethacin-Duloxetine（IN-DUL）,ED₂₅E=2.47 mg/kg,ED₂₅T=6.60 mg/kg;Meloxicam-Pregabalin（MEL-DUL）,ED₂₅E=2.04 mg/kg,ED₂₅T=5.08 mg/kg),and the higher doses did not influence the somatic coordination or motor balance of the mice.In carrageenan-induced inflammatory pain in rats,the analgesic efficacy of IN-PGB and MEL-PGB was improved by the combination,but both combinations were antagonistic,whereas IN-DUL and MEL-DUL were additive or synergistic.In addition,the analgesic effects of the above medication combinations were studied in conjunction with two distinct pain models in this thesis（the formalin test,the acetic acid-induced writhing test）.In conclusion,the combination of indomethacin or meloxicam with pregabalin and indomethacin or meloxicam with duloxetine may have potential therapeutic advantages for the treatment of chemotherapy-induced neuropathic pain as well as favorable therapeutic results for other forms of pain.