Nocebo effects in clinical studies: hints for pain therapy

Abstract

Introduction: Nocebo-induced algesic responses occurring within clinical contexts present a challenge for health care practitioners working in the field of pain medicine.

Objectives: Following the recent research on algesic nocebo effects, the scope of this review is to develop ethically acceptable strategies to help avoid, or at least reduce, nocebo responses within clinical settings.

Methods: We reviewed relevant clinical studies that depict how patient-practitioner interactions may contribute to the reduction of nocebo responses.

Results: A strong algesic nocebo effect may adversely impact a patient's condition by causing decreases in both the efficacy and effectiveness of interventions, as well as by promoting treatment nonadherence and discontinuation. These effects may be triggered through multiple channels and can lead to significant alterations in a patient's perception of pain, consequently producing a weakening of the specific positive effects of pharmacological, psychological, or physical pain-management interventions.

Conclusion: To minimize nocebo effects in clinical settings, we identified and discussed five contextual aspects relevant to the treatment of patients with chronic pain: (1) negative patient-clinician communication and interaction during treatment; (2) emotional burden of patients during treatment with analgesic medication; (3) negative information provided via informational leaflets; (4) cued and contextual conditioning nocebo effects; and (5) patient's lack of positive information. Through an understanding of these elements, many preventive and ethically acceptable clinical actions can be taken to improve multidisciplinary pain treatment outcomes.

Keywords: Hyperalgesia; Nocebo algesia; Nocebo effects; Pain modulation; Pain treatment; clinical implications.

Figure 1.

Placebo and nocebo effects influence pain outcomes. When an analgesic is given, information about its effects shapes the patient's expectation about its efficacy. Negative expectancies about the effect of an analgesic can reduce its efficacy (nocebo effect). When an analgesic is prescribed, it is useful to emphasize positive drug effects and to avoid overemphasizing side effects. Often, patient–clinician communication is characterized by unbalanced information that leans towards negative components. A patient wants the clinician to help relieve the pain and is willing to take the medication, but does not want to experience side effects. The clinician then finds an alternate solution. However, by prescribing a painkiller according to the WHO 3-Step Model for Pain Management (step 1), the health provider may accidentally minimize the medication's efficacy by providing additional unsought information regarding the level of action of the newly recommended drug.

Figure 2.

Interventional acute pain and framing effects. The manner information is presented during an epidural procedure that impacts pain perception in women experiencing labor pain associated with childbirth. Women were told what to expect about the procedure in 2 distinct ways. Group 1 was informed as follows: “You are going to feel a big bee sting; this is the worst part of the procedure”. Conversely, group 2 was given the following instruction: “We are going to give you a local anesthetic that will numb the area and you will be comfortable during the procedure.” The graph shows differences in pain ratings between both groups. Pain was assessed in a blinded fashion. Women in group 2 who were informed with a positive framing about the possibility to experience pain reported significantly less pain than those informed through the standard framing style for the same procedure. Data from Varelmann et al. Varelmann D, Pancaro C, Cappiello EC, Camann WR. Nocebo-induced hyperalgesia during local anesthetic injection. Anesth Analg 2010;110: 868–70. Promotional and commercial use of the material in print, digital or mobile device format is prohibited without the permission from the publisher Wolters Kluwer. Please contact healthpermissions@wolterskluwer.com for further information.

Figure 3.

Graphical abstract. The “Open-Hidden” research paradigm developed by Benedetti et al and Colloca et al is not just an alternative study design but a model that can summarize circumstances of the daily clinical practice impacting the development of the patient's expectancies. A hidden (covert) administration consists of giving a medication without specifying the exact time of administration, for example, throughout a computer-managed infusion pump. An open (overt) administration of a medication takes place in full view and it is perceived by the patient. The latter produces better results than the former type of administration. An administered medication can be perceived by seeing, feeling, smelling, and/or tasting it. The higher the patient's treatment awareness is, the higher is the potential to create positive placebo effects. Thus, any medication can be given in a context in which the patient's expectancies can be either empowered or silenced resulting in turn in better or worse pain outcomes.