This study aimed to create a better understanding of the neurobiological mechanisms underlying the induction of nocebo hyperalgesia. Nocebo hyperalgesia refers to an increased pain perception...Show moreThis study aimed to create a better understanding of the neurobiological mechanisms underlying the induction of nocebo hyperalgesia. Nocebo hyperalgesia refers to an increased pain perception resulting from negative outcome expectations, a phenomenon that can negatively influence a patient’s clinical outcome. Much concerning the mechanisms underlying the induction of nocebo hyperalgesia is still unknown, although it can be hypothesized that NMDA receptor-dependent learning may play a role. The current study tested this hypothesis by pharmacologically manipulating NMDA receptor- dependent learning in healthy participants, expecting that the pharmacological manipulation would facilitate the induction of nocebo hyperalgesia. Participants (n = 50) received either a placebo or an 80 mg dose of D-cycloserine (DCS), a partial NMDA receptor agonist. Nocebo hyperalgesia was induced in both groups with verbal suggestions and a classical conditioning paradigm consisting of an induction and evocation phase. In the induction phase, high intensity heat-pain stimuli were given during trials where a sham electrical stimulation device was supposedly turned on (nocebo trials), while moderate heat-pain stimuli were given during trials where a sham electrical stimulation device was supposedly turned off (control trials). During the evocation phase, only moderate pain stimuli were given. Nocebo hyperalgesia was indicated when participants rated their pain higher during nocebo trials compared to control trials. A significant paired-samples t-test (t (49) = -8.55, p < .001) suggested that nocebo hyperalgesia was successfully induced in both groups, further confirming that nocebo hyperalgesia can be induced by classical conditioning and verbal suggestions. Nevertheless, the pharmacological manipulation of NMDA receptor-dependent learning with 80 mg DCS did not facilitate the magnitude of the induced nocebo hyperalgesia more than a placebo, as indicated by a one-way ANOVA (F (1, 49) = 0.028, p = 0.867). The usability of DCS in nocebo research was discussed, and further research was recommended. It is important that the current study is replicated, possibly with the use of another glutamatergic agent. The results from future studies could play a significant role in diminishing the impact of nocebo hyperalgesia on clinical practice.Show less
Nocebo hyperalgesia can be defined as an increased sensitivity to pain caused by a nocebo effect. Expectancies are fundamental to nocebo effects. How pain is experienced can be modified by...Show moreNocebo hyperalgesia can be defined as an increased sensitivity to pain caused by a nocebo effect. Expectancies are fundamental to nocebo effects. How pain is experienced can be modified by expectancies and avoidance behavior. This is the basis of the fear-avoidance model. The aim of this study was to gain a better understanding of the relationship between pain, expectancies and avoidance behavior. More specifically, we wanted to assess whether negative expectancies induce nocebo hyperalgesia, and whether nocebo hyperalgesia predicts avoidance. A total of 116 participants were included in the study. Participants were randomly assigned to either the control (n = 58) or nocebo group (n = 58). The pain stimuli were administered electrically. In the nocebo group, expectancies about pain stimuli were induced by verbal suggestions and conditioning. The verbal suggestions included telling participants that a specific color cue would increase the intensity. The conditioning consisted of consistently pairing a specific color cue with a higher stimulus. In the control group, no expectancies were induced and stimuli were administered randomly. Avoidance was measured through a pain avoidance task for which the Tower of Hanoi was used. Results indicated a significant interaction between type of color cue and group (F(1,114) = 34.08, p < .001, ηp2 = .230), indicating a significant difference between the pain ratings of the color cues of both groups. Participants in the nocebo group gave higher pain ratings than the control group, indicating that nocebo hyperalgesia increased when negative expectancies were induced. However, nocebo hyperalgesia did not predict avoidance behavior (χ² (1) = .51, p = .477). The results are in line with studies on nocebo effects on pain and add to the importance of verbal suggestions. As pain can be hugely modified by expectancies, it is recommended for clinicians to be mindful of their communication with patients. By effectively managing patients’ expectancies, nocebo effects can be minimized. Results do not completely corroborate the fear-avoidance model. Therefore, future research should focus on developing objective measurement instruments of avoidance. This could provide more insight into the development of pain and improve pain treatments.Show less
Pain is a common complaint that can interfere with daily life severely. Expectations play a crucial role in pain perception. It has been found that fear of pain interacts with these expectations....Show morePain is a common complaint that can interfere with daily life severely. Expectations play a crucial role in pain perception. It has been found that fear of pain interacts with these expectations. Research investigating the influence of fear of pain on pain perception is sparse. The aim of the present study is to investigate whether increased pain sensitivity can be induced by conditioning and verbal suggestion of negative expectations. Moreover, the study investigated if fear of pain could predict increased sensitivity to pain. Data of 27 healthy young adults (22 females) was used in this study. Participants received induction of negative expectations regarding electrical pain. Fear of pain was measured prior to the induction of electrical pain by using the minor pain subscale of the Fear of Pain Questionnaire III. Pain was electrically induced and measured by numerical pain rating scales. The participants were randomized into an experimental (induction of negative expectations) or a control group (expectations not manipulated). The results show that the experimental group scored higher on increased sensitivity to pain than the control group. Therefore, it can be concluded that an increased sensitivity to pain can be induced by a negative expectation learning procedure. This effect is strong and can have a strong negative effect on treatment outcomes. Furthermore, it has been found that fear of pain cannot predict nocebo hyperalgesia. This may relate to the healthy sample. It is important to investigate the relation of expectations, increased pain sensitivity and fear of pain. Doing so optimizes treatment and therefore prevents patients with chronic pain to experience increased pain.Show less
