Different mechanisms underlie the analgesic actions of paracetamol and dipyrone in a rat model of inflammatory pain

Abstract

Background and purpose: The analgesics, paracetamol and dipyrone are weak inhibitors of the cyclooxygenase isoforms 1 or 2 (COX-1, COX-2) but more potent on COX-3. Both are also weak anti-inflammatory agents, relative to their analgesic and antipyretic activities. In a model of inflammatory pain mediated by prostaglandins, both compounds were analgesic. We have analysed this shared effect further in order to elucidate the underlying mechanisms. Experimental approach: Inflammation was induced in one hind paw of rats by intraplantar injection of 250 mg l-carrageenan (CG) and the contralateral paw injected with saline. Nociceptive thresholds to mechanical stimulation were measured immediately before and for 6 h after, injection of CG. The analgesics were s.c. or locally (intraplantar) injected either 30 min before or 2 h after CG. In some groups, naltrexone was injected (s.c. or intraplantar), 1 h before CG. Key results: Pretreatment with paracetamol or dipyrone (60-360 mg kg À1 ) reversed hyperalgesia induced by CG and increased nociceptive threshold in the inflamed paw above the basal level (hypoalgesia). Paracetamol, but not dipyrone, also raised nociceptive thresholds in the non-inflamed paw. Subcutaneous, but not local, administration of naltrexone, a specific opioid antagonist, reversed the hypoalgesia induced by paracetamol, but similar naltrexone treatment had no effect on dipyrone-induced analgesia. Conclusions and implications: Although both paracetamol and dipyrone are inhibitors of COX isoforms and thus of prostaglandin biosynthesis and were analgesic in our model, their analgesic actions were functionally and mechanistically different. Satisfactory mechanisms of action for these analgesics still remain to be established.

Prevention of acute adverse events related to infliximab infusions in pediatric patients

“…It has been suggested that prostaglandins may play a role in these conditions, particularly in the vasodilatation, resulting in flushing (20). The antifebrile agent we used was acetaminophen, which has inhibitory activity to prostaglandins and cyclooxygenase isoform 3 (21,22). The dose of cetirizine, a second-generation H 1 antihistamine, in this study was high (10 mg) when compared with the recommended dosage of 5 mg/day for allergic symptoms (23).…”

Dipirona versus paracetamol no controle da dor pós-operatória

“…Atualmente, a dipirona e o paracetamol são os analgésicos mais prescritos no Brasil 11,12 ; no entanto, a dipirona tem seu uso restrito nos EUA e em vários países da Europa, em razão da possibilidade de causar agranulocitose, complicações gastrointestinais, anemia aplástica e anafilaxia 13,14 .…”

Dipyrone ameliorates behavioural changes induced by unpredictable chronic mild stress: gender differences

“…Acute administration of paracetamol has been shown to cause antidepressant-like effects and display synergistic effect with fluoxetine in FST and tail suspension tests without affect locomotor activity [27]. Dipyron and paracetamol have been proposed to reveal similar analgesic mechanism such as inhibition of COX enzymes in the brain, interaction with endogenous opioid and cannabinoid systems, arginine-nitric oxide-cGMP pathway, 5-HT activation [6]. Impairments in these endogenous systems also produce depressive states as indicated in clinically and experimentally studies [28].…”

“…Serotonergic-noradrenergic system, arginine-NO-cGMP pathway, neuronal potassium channels and inflammatory cytokine levels have been suggested as possible mechanisms for the analgesic action of dipyrone [4][5][6]. Other central effects, distinct from this analgesic effect, have been evaluated.…”