Dissociative and Analgesic Properties of Ketamine Are Independent

Background Ketamine is a dissociative anesthetic with analgesic properties. Ketamine’s analgesic properties have been suggested to result from its dissociative properties. To the authors’ knowledge, this postulate is unsubstantiated. The authors hypothesize that the dissociative and analgesic properties of ketamine are independent. Methods The authors conducted a single-site, open-label study of ketamine anesthesia (2 mg/kg) in 15 healthy subjects. Midazolam was administered at a prespecified time point to attenuate dissociation. The authors longitudinally assessed precalibrated cuff pain intensity and quality using Patient-Reported Outcomes Measurement Information System questionnaires, and dissociation, using the Clinician Administered Dissociative States Scale. Mixed effects models were used to assess whether dissociation accounted for the effect of ketamine on pain intensity and quality. Results The dissociation model demonstrated an inverted U-shaped quadratic relationship between time and dissociation scores. Additive to this effect, midazolam reduced the dissociation adjusted means by 10.3 points (95% CI, 3.4 to 17.1; P = 0.005). The pain intensity model also demonstrated a U-shaped quadratic relationship between time and pain intensity. When the pain intensity model was reanalyzed with dissociation scores as an additional covariate, the dissociation term was not retained in the model, and the other effects were preserved in direction and strength. This result was conserved for nociceptive and neuropathic pain quality. Conclusions Ketamine’s analgesic properties are not exclusively caused by dissociation. Thus, ketamine may be used as a probe to advance our knowledge of dissociation independent neural circuits that encode pain. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

A Process Dissociation Model of Implicit Rapid Revision in Response to Diagnostic Revelations

Previous research has demonstrated that implicit evaluations can be reversed with exposure to a single impression-inconsistent behavior. But what exactly is changing when perceivers encounter diagnostic revelations about someone? One possibility is that rapid changes are occurring in the extent to which perceivers view the person positively or negatively. Another possibility is that they override the expression of initial evaluations through control-oriented processes. We conducted three studies (one preregistered) that used multinomial process trees to distinguish between these possibilities. We find consistent support across two different implicit measures that diagnostic behaviors result in rapid changes in evaluative processes. We obtained only inconsistent evidence for effects on more control-oriented processes. These findings thus help to reveal the cognitive processes underlying rapid implicit revision. Implications for theoretical perspectives on implicit attitudes are discussed.