2.2.1. Human Studies
A number of excellent reviews have been published on sex differences in opioid analgesia/antinociception (Craft, 2008; Dahan et al., 2008; Fillingim et al., 2009; Bodnar & Kest, 2010; Niesters et al., 2010; Rasakham & Liu-Chen, 2011; Lee & Ho, 2013; Loyd & Murphy, 2014; Nasser & Afify, 2019; Mogil, 2020), and several reviews have specifically addressed sex differences in pain sensitivity and sensitivity to opioid analgesia in humans (Craft, 2008; Fillingim et al., 2009; Lee & Ho, 2013; Loyd & Murphy, 2014; Mogil, 2020; Niesters et al., 2010;). Clinically, women report more pain and require significantly more morphine to alleviate pain than men (Aubrun et al., 2005; Cepeda & Carr, 2003; but see Chia et al., 2002). Similarly, women have lower pain thresholds and pain tolerances than men on laboratory pain measures (Al’Absi et al., 2004; Fillingim et al., 2004; Fillingim et al., 2005; Zacny & Beckham, 2004). Laboratory studies measuring sex differences in opioid-induced analgesia are more equivocal, but generally report that men are more sensitive to opioid analgesia on some (but not all) pain measures (Fillingim et al., 2004; Zacny & Beckham, 2004).