Interaction between hyperbaric oxygen therapy and prostaglandin synthesis inhibition in the formalin pain test

Abstract

BackgroundPain is the main symptom of inflammatory diseases, such as diabetes mellitus, hypertension, osteoarthritis among others. Lipopolysacaccharide from E. coli (LPS) has been used to induce an inflammatory process. Prostaglandins has a role in inflammation so that NSAIDs are useful pharmacological tools to treat it. Hyperbaric oxygen therapy (HBOT) has also been used in some of these diseases. However, information about pharmacological interaction with HBOT and its mechanism is scarce. So, the purpose of this work was to study the interaction between LPS, HBOT and NSAIDs using a formalin pain test.Methods96 adults male Wistar rats (150 to 200 g) were used and 2 groups treated with LPS or its vehicle were formed and each of them was divided in the next subgroups (n=8 each): Control, indomethacin, rofecoxib, HBOT, HBOT/indomethacin and HBOT/rofecoxib. 20 μL of 2% formalin was injected into the plantar surface of the right hind paw. Then nociceptive behavior was evaluated as the number of flinches in 1 min every 5 for 60 min. LPS and HBOT were applied 4 and 2.5 h prior to formalin respectively. Additionally, PGE2 and PGI2 was quantified using RP‐HPLC‐UV.ResultsFormalin produces a nociceptive behavior that decreased in the first 10 min (phase I) and in the next 50 increased to a plateau and then become to reduce (phase II, inflammatory). LPS increased and HBOT and drugs treatment reduced the phase II, while PGI2 levels were increased with LPS and reduced with HBOT and drugs. The HBOT seems to increase the indomethacin antinociceptive effect but HBOT effect was lesser than control and levels of prostaglandins were similar than in absence of HBOT. LPS treatment reduced the rofecoxib and HBOT effect increasing PGE2 and PGI2 levels respectively. Finally, when HBOT is associated with LPS and indomethacin, an increase on AUC of formalin and PGI2 levels was observed.ConclusionsThe HBOT and prostaglandin synthesis inhibition were effective antinociceptive interventions. However, indomethacin but not rofecoxib increased the HBOT antinoceptive effect diminishing PGI2 levels. In presence of an inflammatory process, the effect of HBOT and rofecoxib but no indomethacin, the antinociception was lost due to an increase in prostaglandin synthesis. Therefore, there are an interaction between HBOT and PG synthesis inhibition and the presence of inflammation reduced the beneficial effects of physical or pharmacological interventions.Support or Funding InformationThe authors would like to acknowledge CONACYT (557096) for their financial support