Assessment of the antinociceptive and ulcerogenic activity of the tapentadol–diclofenac combination in rodents

Abstract

Preclinical Research & Development The objective of the present study was to evaluate the tapentadol-diclofenac combination in three dose-ratios in the mouse acetic acid-induced visceral pain and their ulcerogenic activity on the stomachal mucous. Dose-response curves were generated for tapentadol, diclofenac, and their combination in the acetic acid-induced writhing test in mice. Moreover, the stomachs of animals were surgically removal and gastrointestinal ulcerogenic action of the combination was assessed. The isobolographic analysis, interaction index, and ANOVA were used to analyze the data. The isobolographic analysis and interaction index showed a similar antinociceptive activity for the three combinations of the analgesic mixture. Moreover, tapentadol and the proportions 1:1 or 3:1 of the analgesic combination caused a mild gastrointestinal damage. These data indicate that the systemic co-administration of tapentadol and diclofenac produced a synergistic interaction in the acetic acid-induced visceral pain test with an acceptable gastric damage profile in mice.

Participation of ATP‐sensitive K+ channels and μ‐opioid receptors in the antinociceptive synergism of the paracetamol–tapentadol co‐administration in the formalin‐induced pain assay in mice

“…All these findings were confirmed using both isobolographic analysis and interaction index. Similar results have been observed when other NSAIDs and tapentadol were used in somatic and visceral animal pain models (Barreras‐Espinoza et al, ; Zapata‐Morales et al, , ) as well as when paracetamol has been used in combination with other opioid analgesics in the formalin and acetic acid assays in rodents (Fernández‐Dueñas, Poveda, Sánchez, & Ciruela, ; Janovsky and Krsiak, ; Miranda, Puig, Dursteler, Prieto, & Pinardi, ; Miranda, Noriega, & Prieto, ).…”

“…It has been shown that the effect of a two‐analgesic combination depends on the proportions in which this combination is tested, obtaining synergistic effects, additives as well as antagonisms. This kind of studies using several proportions of an analgesic combination are essential, particularly when human clinical trials will be carried out, the information of animal models could be the only guide to define the experimental doses (Barreras‐Espinoza et al, ; Maves, Pechman, Meller, & Gebhart, ; Zapata‐Morales et al, , ).…”

“…Recently, our research group has demonstrated that the co‐administration of tapentadol and NSAIDs—such as ketorolac and diclofenac—produces a potentiation of the antinociceptive activity in comparison to the individual effect of each drug in animal pain models (Barreras‐Espinoza et al, ; Zapata‐Morales et al, ; Zapata‐Morales, Alonso‐Castro, Granados‐Soto, Sánchez‐Enriquez, & Isiordia‐Espinoza, ). For instance, the ketorolac–tapentadol combination produced antinociception by the participation of opioid receptors and ATP‐sensitive K + channels in the formalin‐induced trigeminal pain model in mice (Barreras‐Espinoza et al, ).…”

“…For instance, the ketorolac–tapentadol combination produced antinociception by the participation of opioid receptors and ATP‐sensitive K + channels in the formalin‐induced trigeminal pain model in mice (Barreras‐Espinoza et al, ). Moreover, the diclofenac–tapentadol combination showed a synergistic antinociceptive action in the acetic acid‐induced visceral pain model with a gastric injury similar to tapentadol alone but with lower gastric injury compared to diclofenac alone (Zapata‐Morales et al, ). Following this research line, the objective of this study was to assess the antinociceptive activity and the mechanism of action of the paracetamol–tapentadol combination in the second phase of the formalin test in mice.…”

Antinociception and less gastric injury with the dexketoprofen‐tapentadol combination in mice

“…Co‐administration of NSAIDs—such as ketorolac, diclofenac, and acetaminophen—and tapentadol has previously been shown to produce synergistic analgesic effects and a better safety profile of the drugs combination when compared with each individual drug in some pain mouse models [12–15]. Thus, the purpose of this study was to evaluate the possible synergistic interaction between dexketoprofen and tapentadol in the writhing test in mice.…”