LAUSR

In the target article “Telling the Truth About Pain: Informed Consent and the Role of Expectation in Pain Intensity,” evidence of pain as “a psychological phenomenon causally related to physical or biological changes” supports the use of placebo analgesia to mitigate pain responses among patients (Gligorov 2018). An important extension of this discussion calls us to consider the effects of placebo analgesia in the context of nocebo effects. The interaction of placebo and nocebo effects impacts practice, supports the ethical justification for the use of placebo analgesia, and shows that while a patientcentered approach for the reduction of nocebo may be appropriate when considering nondisclosure of medication side effects, those ethical demands may be mitigated when considering the use of placebo analgesia. Hahn (1997) importantly distinguished that placebo effects occur when positive expectations lead to a positive outcome, while nocebo effects occur when negative expectations lead to negative outcomes. Furthermore, placebos are most classically understood in the context of inert agents having similar effects in one cohort as a therapeutic agent in a different cohort. Nocebos, on the other hand, are often discussed in the context of pharmaceutical side effects that occur as a result of the patient’s expectations, not of pharmacological origin. Gligorov centers her discussion on a different clinical scenario: patients who are preparing to undergo painful procedures. In this context, especially, one must be cognizant of both placebo and nocebo effects when considering the use of placebo analgesia. Patients who undergo any invasive procedure, (e.g., venipuncture, lumbar puncture, bladder catheterization, etc.), will have an expectation of pain irrespective of any contextualization or framing of the incipient pain caused by the provider. Thus, it follows that negative expectations enable a potential nocebo effect. Viewed in this context, administration of placebo analgesia (provision of a new, positive expectation) may mitigate the nocebo effect (i.e., a negative expectation). This is contrasted from the traditional understanding of placebo, wherein a pharmacologically inert agent provides a positive expectation (e.g., alleviation of a headache), removed from the context of an imminent negative expectation (painful procedures). The salient difference is that placebos are given for an extant condition where the nocebo effect does not arise de novo (i.e., it is preceded by an intervention). This distinction allows us to consider both the placebo effect and the nocebo effect when discussing the ethics of placebo analgesia. Gligorov effectively justifies the use of placebo analgesia as a placebo by showing that placebo analgesia is not inert, but instead uses the same biochemical pathways as pharmacologically active analgesia. Therefore, the use of placebo analgesia is not deceptive. We extend the ethical justification of the use of placebo analgesia as a tool to counteract the nocebo effect. Gligorov and others (Wells and Kaptchuk 2012) have argued for contextualization and framing of medication side effects or harmful procedures to limit nocebo effects. Others, prioritizing nonmaleficence over patient autonomy, have made stronger claims for the nondisclosure of some medication side effects (Cohen 2014), as long as autonomy is preserved at a later date in followup physician visits (Fortunato et al. 2017). The use of placebo analgesia is less ethically problematic than selective