An analysis of factors that contribute to the magnitude of placebo analgesia in an experimental paradigm

Price, Donald D.; Milling, Leonard S.; Kirsch, Irving; Duff, Ann; Montgomery, Guy H.; Nicholls, Sarah S.

doi:10.1016/s0304-3959(99)00081-0

Cited by 508 publications

(349 citation statements)

References 16 publications

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“…Previous work has shown that the prospect of reduced pain can reduce the pain reported in response to a noxious stimulus. [84][85][86][87][88] The "inclusion/ exclusion" session provided an expectation that head pain would increase during the interventions and cease immediately after cessation of the technique. However, participants had no prior expectation of the likely course of referred head pain as the technique was sustained.…”

Section: Discussionmentioning

confidence: 99%

Cervical Referral of Head Pain in Migraineurs: Effects on the Nociceptive Blink Reflex

Watson

Drummond

2014

Headache

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Objective.-To investigate cervical, interictal reproduction of usual head pain and its effect on the nociceptive blink reflex in migraineurs.Background.-Anatomical and neurophysiological studies in animals and humans have confirmed functional convergence of trigeminal and cervical afferent pathways. Migraineurs often present with occipital and neck symptoms, and cervical pain is referred to the head in most cases, suggesting that cervical afferent information may contribute to headache. Furthermore, the effectiveness of greater occipital nerve blockade in migraine and demonstrable modulation of trigeminal transmission following greater occipital nerve blockade suggest an important role for cervical afferents in migraine. However, to what extent cervical afferents contribute actively to migraine is still unknown.Methods.-The passive accessory intervertebral movements of the atlanto-occipital and C2-3 spinal segments of 15 participants (14 females, 1 male; age 24-44 years, mean age 33.3 years) with migraine were examined interictally. During 1 session, either the atlanto-occipital or C2-3 segment was examined, resulting in referred usual head pain, while in another session, pressure was applied over the common extensor origin (lateral epicondyle of the humerus) of the ipsilateral arm. Each intervention was repeated 4 times. The nociceptive blink reflex to a supraorbital electrical stimulus was elicited ipsilaterally during both sessions before and during each intervention. The main outcome variables were the number of recorded blinks, area under the curve and latencies of the R2 components of the nociceptive blink reflex. Participants also rated the intensity of referred head pain and the supraorbital stimulus on a scale of 0-10, where 0 = "no pain" and 10 = "intolerable pain," and rated the intensity of applied pressure where 0 = "pressure but no pain" and 10 = "intolerable pain."Results.-Participants reported a significant reduction in local tenderness ratings across the 4 trials for the cervical intervention but not for the arm (P = .005). The cervical intervention evoked head pain in all participants. As the cervical intervention was sustained, head pain decreased significantly from the beginning to the end of each trial (P = .000) and from the beginning of the first trial to the end of the last (P = .000). Pain evoked by the supraorbital stimulus was consistent from baseline to across the 4 trials (P = .635) and was similar for the cervical and arm interventions (P = .072). The number of blinks decreased significantly across the experiment (P = .000) and was comparable in the cervical and arm interventions (P = .624). While the R2 area under the curve decreased irrespective of intervention (P = .000), this reduction was significantly greater for the cervical intervention than when pressure was applied to the arm (P = .037). Analysis of the R2 latencies revealed a notable increase across the experiment (P = .037). However, this increase was significantly greater following the cervical than arm intervention (P ...

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Section: Discussionmentioning

confidence: 99%

Cervical Referral of Head Pain in Migraineurs: Effects on the Nociceptive Blink Reflex

Watson

Drummond

2014

Headache

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“…As can be expected, the pain ratings in both groups were identical from day 1 until day 5, and only then diverged significantly on days 6 to 8: The control group habituated and the context group did not. The placebo effect may occur through both expectation and conditioning mechanisms (Colloca and Benedetti, 2005), and a correlation between the degree of expected treatment effect and the subsequent placebo-induced analgesia has been observed (Price et al, 1999). Importantly, we did not use learning or conditioning paradigms, i.e., the negative information was only once given verbally.…”

Section: Discussionmentioning

confidence: 99%

Insular Cortex Activity Is Associated with Effects of Negative Expectation on Nociceptive Long-Term Habituation

Rodriguez-Raecke

Doganci²,

Breimhorst³

et al. 2010

J. Neurosci.

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It is generally accepted that acute painful experience is influenced by context information shaping expectation and modulating attention, arousal, stress, and mood. However, little is known about the nature, duration, and extent of this effect, particularly regarding the negative expectation. We used a standardized longitudinal pain paradigm and painful heat test stimuli in healthy participants over a time course of 8 consecutive days, inducing nociceptive habituation over time. Thirty-eight healthy volunteers were randomly assigned to two different groups. One group received the information that the investigators expected the pain intensity to increase over time (context group). The other group was not given any information (control group). All participants rated the pain intensity of the daily standardized pain paradigm on a visual analog scale. In agreement with previous studies the pain ratings in the control group habituated over time. However, the context group reported no change of pain ratings over time. Functional imaging data showed a difference between the two groups in the right parietal operculum. These data suggest that a negative context not only has an effect on immediate pain but can modulate perception of pain in the future even without experience/conditioning. Neuronally, this process is mediated by the right opercular region.

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“…After 15 min waiting time (allegedly for the medication to take effect), the placebo analgesic effect was amplified by a classic conditioning procedure commonly used and proven to be effective in placebo analgesia studies (51). More specifically, participants were exposed to a series of four stimuli delivered with an intensity of stimuli rated between "3" and "4" during the calibration procedure.…”

Section: Methodsmentioning

confidence: 99%

Placebo analgesia and its opioidergic regulation suggest that empathy for pain is grounded in self pain

Rütgen

Seidel

Silani

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

193

218

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Empathy for pain activates brain areas partially overlapping with those underpinning the first-hand experience of pain. It remains unclear, however, whether such shared activations imply that pain empathy engages similar neural functions as first-hand pain experiences. To overcome the limitations of previous neuroimaging research, we pursued a conceptually novel approach: we used the phenomenon of placebo analgesia to experimentally reduce the first-hand experience of pain, and assessed whether this results in a concomitant reduction of empathy for pain. We first carried out a functional MRI experiment (n = 102) that yielded results in the expected direction: participants experiencing placebo analgesia also reported decreased empathy for pain, and this was associated with reduced engagement of anterior insular and midcingulate cortex: that is, areas previously associated with shared activations in pain and empathy for pain. In a second step, we used a psychopharmacological manipulation (n = 50) to determine whether these effects can be blocked via an opioid antagonist. The administration of the opioid antagonist naltrexone blocked placebo analgesia and also resulted in a corresponding "normalization" of empathy for pain. Taken together, these findings suggest that pain empathy may be associated with neural responses and neurotransmitter activity engaged during first-hand pain, and thus might indeed be grounded in our own pain experiences.T here is widespread consensus that empathy recruits brain structures that are also involved in the first-hand experience of the emotion for which one is showing empathy. For example, in the domain of pain, recent image-based and coordinate-based meta-analyses of functional MRI (fMRI) studies have shown that sharing the pain of others consistently activates the bilateral anterior insular (AI) and anterior midcingulate cortex (aMCC) (1). The AI and aMCC are key areas of the network of areas activated by pain, and their activity has been directly related to the affective-motivational component of pain (2). The observation of such shared neural activations has therefore motivated simulationist models, such as the shared representations account of empathy (see refs. 3-5 for review), which propose that we come to understand the feelings of others by engaging the same mental representations as when directly experiencing the emotion with which we are empathizing.However, neuroimaging alone cannot provide sufficient empirical support for such claims because fMRI activation of the same brain area does not necessarily imply equivalence of mental representations and neural functions (see ref. 6 for review). Areas such as the aMCC and AI, for example, are not only activated by pain, but also by phenomena as distinct as cognitive control and responding to salient events in general (see refs. 7-9 for review). This ambiguity is a result of inherent methodological limitations. First, fMRI has mostly been used as a correlational method that identifies neural responses co-occurring with certain c...

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An analysis of factors that contribute to the magnitude of placebo analgesia in an experimental paradigm

Cited by 508 publications

References 16 publications

Cervical Referral of Head Pain in Migraineurs: Effects on the Nociceptive Blink Reflex

Cervical Referral of Head Pain in Migraineurs: Effects on the Nociceptive Blink Reflex

Insular Cortex Activity Is Associated with Effects of Negative Expectation on Nociceptive Long-Term Habituation

Placebo analgesia and its opioidergic regulation suggest that empathy for pain is grounded in self pain

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