Pain and the Placebo: What We Have Learned

Hoffman, Ginger A.; Harrington, Anne

doi:10.1353/pbm.2005.0054

Cited by 116 publications

(68 citation statements)

References 41 publications

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“…It is likely that most fMRI studies and particularly those that employ repeated noxious stimulation have an implicit expectancy component. Previous work has shown that expectancy for pain (versus no pain) enhances the perceived intensity of a somatosensory stimulus (Benedetti et al, 1997;Price, 1999;Sawamoto et al, 2000) and that expectancy for reduced pain (e.g., placebo) can reduce the pain reported in response to a noxious stimulus (Voudouris et al, 1990;Price et al, 1999;Colloca and Benedetti, 2005;Hoffman et al, 2005;Koyama et al, 2005). Here, we confirm and extend those studies by demonstrating that the level of expected pain intensity significantly alters perceived pain intensity when the comparison is between two noxious thermal stimuli of slightly different intensity.…”

Section: Discussionsupporting

confidence: 85%

Isolating the Modulatory Effect of Expectation on Pain Transmission: A Functional Magnetic Resonance Imaging Study

Keltner

Furst²,

Fan³

et al. 2006

J. Neurosci.

320

223

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We use a novel balanced experimental design to specifically investigate brain mechanisms underlying the modulating effect of expected pain intensity on afferent nociceptive processing and pain perception. We used two visual cues, each conditioned to one of two noxious thermal stimuli [ϳ48°C (high) or 47°C (low)]. The visual cues were presented just before and during application of the noxious thermal stimulus. Subjects reported significantly higher pain when the noxious stimulus was preceded by the high-intensity visual cue. To control for expectancy effects, for one-half of the runs, the noxious thermal stimuli were accompanied by the cue conditioned to the other stimulus. Comparing functional magnetic resonance imaging blood oxygenation level-dependent activations produced by the high and low thermal stimulus intensities presented with the high-intensity visual cue showed significant activations in nociceptive regions of the thalamus, second somatosensory cortex, and insular cortex. To isolate the effect of expectancy, we compared activations produced by the two visual cues presented with the high-intensity noxious thermal stimulus; this showed significant differences in the ipsilateral caudal anterior cingulate cortex, the head of the caudate, cerebellum, and the contralateral nucleus cuneiformis (nCF). We propose that pain intensity expectancy modulates activations produced by noxious stimuli through a distinct modulatory network that converges with afferent nociceptive input in the nCF.

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Section: Discussionsupporting

confidence: 85%

Isolating the Modulatory Effect of Expectation on Pain Transmission: A Functional Magnetic Resonance Imaging Study

Keltner

Furst²,

Fan³

et al. 2006

J. Neurosci.

320

223

View full text Add to dashboard Cite

show abstract

“…In this study, we focused our analysis on changes in pain and pain-related disability, regardless of the treatment or mechanism of action. It is quite possible that a strong placebo effect, as is often seen in chronic pain (Seeley, 1990;Hoffman et al, 2005), contributed to the improved outcomes observed in this study. Another important question is as follows: Are the changes in left DLPFC and elsewhere related to pain modulation?…”

Section: Future Directionsmentioning

confidence: 84%

Effective Treatment of Chronic Low Back Pain in Humans Reverses Abnormal Brain Anatomy and Function

et al. 2011

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Chronic pain is associated with reduced brain gray matter and impaired cognitive ability. In this longitudinal study, we assessed whether neuroanatomical and functional abnormalities were reversible and dependent on treatment outcomes. We acquired MRI scans from chronic low back pain (CLBP) patients before (n ϭ 18) and 6 months after (spine surgery or facet joint injections; n ϭ 14) treatment. In addition, we scanned 16 healthy controls, 10 of which returned 6 months after the first visit. We performed cortical thickness analysis on structural MRI scans, and subjects performed a cognitive task during the functional MRI. We compared patients and controls, as well as patients before versus after treatment. After treatment, patients had increased cortical thickness in the left dorsolateral prefrontal cortex (DLPFC), which was thinner before treatment compared with controls. Increased DLPFC thickness correlated with the reduction of both pain and physical disability. Additionally, increased thickness in primary motor cortex was associated specifically with reduced physical disability, and right anterior insula was associated specifically with reduced pain. Left DLPFC activity during an attention-demanding cognitive task was abnormal before treatment, but normalized following treatment. These data indicate that functional and structural brain abnormalities-specifically in the left DLPFC-are reversible, suggesting that treating chronic pain can restore normal brain function in humans.

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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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Pain and the Placebo: What We Have Learned

Cited by 116 publications

References 41 publications

Isolating the Modulatory Effect of Expectation on Pain Transmission: A Functional Magnetic Resonance Imaging Study

Isolating the Modulatory Effect of Expectation on Pain Transmission: A Functional Magnetic Resonance Imaging Study

Effective Treatment of Chronic Low Back Pain in Humans Reverses Abnormal Brain Anatomy and Function

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

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