Sex differences in analgesic response to ibuprofen are influenced by expectancy: A randomized, crossover, balanced placebo‐designed study

Abstract

We found no sex difference in baseline pain threshold or tolerance levels. When partitioned by sex and expectancy state, analgesia only occurred in males during positive expectancy states at 2, 3 and 4 h post-placebo, and at 1 and 2 h post-ibuprofen. The time course of analgesic action in males was as expected considering the pharmacokinetic profile of ibuprofen. Our study found that dosages of 800 mg of ibuprofen are ineffective in producing analgesia in women regardless of their expectations. We hypothesize that ibuprofen analgesia is produced by a combination of specific pharmacological effects and a non-specific beta endorphin-mediated placebo effect. Whatever the mechanism responsible for the analgesic response seen in males, this research re-emphasizes the importance of psychological factors in determining drug response. It also shows that these factors can differ between men and women, and thus the contribution of psychological factors on analgesia needs to be seriously re-evaluated.

Coadministration of indomethacin and minocycline attenuates established paclitaxel-induced neuropathic thermal hyperalgesia: Involvement of cannabinoid CB1 receptors

“…In the current study indomethacin lacked activity against paclitaxel-induced thermal hyperalgesia in female mice but had some activity against the hyperalgesia in male mice. Our findings concur with those of other groups that reported sex differences in response of humans to the analgesic activities of NSAIDs, where some NSAIDs were found to be ineffective against pain in females whilst they were effective in males293031.…”

An ecological study of the extent and factors associated with the use of prescription and over-the-counter codeine in Australia

“…However, the study did not distinguish specifically between OTC codeine use and other OTC analgesics. It has been suggested that psychological factors play an important role in determining analgesic response, with sex differences observed between males and females, potentially leading to differences in medicine choice and access patterns [39]. Furthermore, in the last 10 years, changing patterns have been observed among people presenting to treatment services for codeine dependence.…”

Placebo and Active Treatment Additivity in Placebo Analgesia: Research to Date and Future Directions

“…Fig. 4 shows the results of this search, in which only seven studies were found to have used one of these designs in placebo analgesia (Aslaksen, Zwarg, Eilertsen, Gorecka, & Bjørkedal, 2015; Atlas et al, 2012; Berna et al, 2017; Butcher & Carmody, 2012; Kam-Hansen et al, 2014; Lund, Vase, Petersen, Jensen, & Finnerup, 2014; Schenk, Sprenger, Geuter, & Buchel, € 2014). …”

“…Four of the seven studies used the balanced placebo design (Aslaksen et al, 2015; Butcher & Carmody, 2012; Kam-Hansen et al, 2014; Schenk et al, 2014), while two used the balanced open-hidden design (Atlas et al, 2012; Lund et al, 2014). The final study conducted by Berna et al (2017) used a novel design here described as a “balanced active placebo design.” In this variation of the balanced placebo design, receipt of an active treatment or placebo are factorially crossed with administration of an active placebo or placebo, with the second factor replacing the instructions of treatment allocation typical of the balanced placebo design.…”

“…Three studies examined lidocaine, a sodium channel blocker (Aslaksen et al, 2015; Lund et al, 2014; Schenk et al, 2014), two examined NSAIDs, namely diclofenac and ibuprofen (Berna et al, 2017; Butcher & Carmody, 2012), one examined maxalt, a triptan used to treat migraines (Kam-Hansen et al, 2014), and one examined the opioid remifentanil (Atlas et al, 2012). …”