Acetaminophen (Paracetamol): Use beyond Pain Management and Dose Variability

The influence of environmental and core temperature on cyclooxygenase and PGE2 in healthy humans

“…PGE2 did not change significantly at any time point within condition compared to baseline; rejecting hypothesis (vi). Significant relationships between COX2/PGE2 in COLD (p = 0.0012), COX2/PGE2 (p = 0.0243) and PGE2/Tc (p = 0.0079) in COLD/TN [(collapsed by condition and time) NB: results from this analysis should be tempered given the difference in environmental temperature between conditions] were seen, with higher PGE2 concentrations associated with higher Trec compared to baseline, supporting the premise of a COX/PGE2 thermogenic pathway as hypothesized here and elsewhere 19 , 35 . The nuances of these biochemical responses and changes in Trec regulation will subsequently be discussed.…”

“…in an afebrile state) and performs ‘housekeeping’ functions to maintain homeostasis 51 , 52 thus, would be the catalyst for increases in PGE2 and thus rises in Tc. However, COX1 was not detected [despite the high sensitivity (0.225 ng ml −1 ) of the ELISA kit employed] and within the present design it appears not to behave in the manner inferred in humans 19 , 35 regarding homeostatic Tc control. COX2 is widely accepted as an inducible form of COX and is upregulated in pathological states (i.e.…”

“…There is currently no human data to support an afebrile COX1/PGE2 thermogenic pathway (i.e. Tc maintenance/increase 35 ) however, a reduction in PGE2 in rodents is synonymous with Tc reduction 20 , 21 , 36 . Following acetaminophen [paracetamol (ACT)] administration, a potent in vivo COX/PGE2 inhibitor in humans 37 and rodents 20 , 21 , 36 , a reduction in Tc (up to 3.9 °C) was simultaneous with up to 96% reductions in PGE2 in afebrile rodents housed below their thermoneutral zone (TNZ 20 , 21 , 36 ); “ the TNZ is a range of ambient temperature at which temperature regulation is achieved only by control of sensible heat loss, i.e., without regulatory changes in metabolic heat production or evaporative heat loss.” 38 .…”

“…Thus, this study will explore the COX/PGE2 pathway (COX1, COX2 and PGE2 concentrations) in response to acute exposure to different environmental conditions (cold, hot and thermoneutral) that challenge or maintain Tc. Indeed, deductive research designs have been called for 35 and are thus required to elucidate the influence of COX/PGE2 on human Tc regulation. It is hypothesized that rectal temperature (Trec) will: (i) significantly increase in a hot environment; (ii) remain stable in a cold (as seen elsewhere 22 , 23 ) and (iii) thermoneutral environment.…”

Should patients with rheumatic diseases take pain medication in order to engage in exercise?

“…muscle mass increase) that can improve balance, cachexia (loss of muscle mass), functional disability, and other outcomes in people with RMDs. Significantly fewer side-effects are seen with the use of acetaminophen (paracetamol) vs. NSAIDs in athletes [22]. However, in patients with RMDs that are already subjected to polypharmacy [23], this may not be an absolutely safe approach, as increases in acetaminophen use could potentially result in further side effects.…”