Anthony Jones | The University of Manchester (original) (raw)
Papers by Anthony Jones
Background / Purpose: The experience of pain comprises both sensory and affective components ( Me... more Background / Purpose: The experience of pain comprises both sensory and affective components ( Melzack R &Wall PD (1965)). Selective attention to the sensory component of pain has been found to reduce the perceived intensity and affective response to pain in individuals who are anxious or fearful about pain, but increases these variables in those who are not (Brown CA and Jones AKP (2010), Hadjistavropoulos HD et al (2000)). The aim of this study was to investigate the neural correlates of this interaction between attention and anxiety.It was expected that anxiety-related neural activity in the pain matrix would be reduced by focussing attention on the sensory component of pain relative to the emotional component. Main conclusion: Attending to pain sensation reduces the relationship between anxiety and pain perception. This interaction is related to differences in cortical processing during early anticipation of pain. Specifically, attending to pain sensation reduces right Insula ac...
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2004
The accuracy of the inverse solution that finds the spatial location of the generating sources fr... more The accuracy of the inverse solution that finds the spatial location of the generating sources from averaged scalp-recorded event related potentials (ERPs) relies on assumptions about the ERP signals and the sources. We provide evidence that using independent component analysis (ICA) as a signal decomposition filter prior to applying the inverse solution reveals sources that cannot be detected by conventional source localisation methods. Five clusters of sources emerged: a single source cluster in caudal cingulate and bilateral sources in secondary somatosensory cortex (SII), inferior parietal cortex, premotor cortex and insular cortex. The locations of the source dipoles were consistent with findings using fMRI and PET but have not all been previously detected in a single electrophysiological study. In addition, the time-course of the activation of these dipoles was estimated. The results suggest that using ICA to localise single trial data is a powerful tool for exploring the spat...
Handbook of experimental pharmacology, 2014
Placebo analgesia has become a well-studied phenomenon that encompasses psychology, physiology an... more Placebo analgesia has become a well-studied phenomenon that encompasses psychology, physiology and pharmacology. In this chapter we explore the complex interactions between these disciplines in order to argue that the placebo response is more than a simple change in perception but is a cognitive style driven by prior expectations. The expectation of treatment effect is shaped by prior information and prior experience which our brain uses to predict future events. In the case of placebo analgesia the prediction of pain relief overrules the actual feeling of pain leading to a decrease in pain sensation. This altered sensation can be attributed to personality traits, altered error monitoring processes, changes in anticipatory responses to pain and activation of the endogenous opioid system. In conclusion we discuss how altered sensory processing by descending pain modulation may play a part in placebo analgesia and how the loss of the brains prefrontal regions can make it impossible to...
Current rheumatology reports, 2012
Rheumatic pain and, in particular, rheumatoid arthritis, osteoarthritis and fibromyalgia, are com... more Rheumatic pain and, in particular, rheumatoid arthritis, osteoarthritis and fibromyalgia, are common and debilitating chronic pain syndromes. Recently, human functional neuroimaging, for example EEG, fMRI, and PET has begun to reveal some of the crucial central nervous system mechanisms underlying these diseases. The purpose of this review is to summarise current knowledge on the brain mechanisms of rheumatic pain revealed by functional neuroimaging techniques. The evidence suggests that two mechanisms may be largely responsible for the clinical pain associated with these rheumatic diseases: abnormalities in the medial pain system and/or central nervous system sensitisation and inhibition. If we can understand how functioning of the central nociceptive system becomes altered, even in the absence of peripheral nociceptive input, by using functional neuroimaging techniques, in the future we may be able to develop improved, more effective treatments for patients with chronic rheumatic ...
Surface and Coatings Technology, 2000
Two new coatings based on graphite and MoS 2 have been developed. They combine low friction with ... more Two new coatings based on graphite and MoS 2 have been developed. They combine low friction with high hardness, high load capacity and exceptionally low wear. Both coatings act as solid lubricants, providing protection for both the coated surface and any opposing uncoated surface. The coatings are finding application in improving the general performance of cutting and forming tools and also make possible high-speed machining. The graphite-based coatings have exceptional wear properties under water or oil and results from wear tests under a wide range of conditions are given. A number of practical applications are given, including the protection of artificial hip joints. The advantages offered by the use of such coatings for many mechanical components are demonstrated.
PLoS ONE, 2013
The lack of clear understanding of the pathophysiology of chronic pain could explain why we curre... more The lack of clear understanding of the pathophysiology of chronic pain could explain why we currently have only a few effective treatments. Understanding how pain relief is realised during placebo analgesia could help develop improved treatments for chronic pain. Here, we tested whether experimental placebo analgesia was associated with altered resting-state cortical activity in the alpha frequency band of the electroencephalogram (EEG). Alpha oscillations have been shown to be influenced by top-down processes, which are thought to underpin the placebo response.
PAIN, 2008
Expectations about the magnitude of impending pain exert a substantial effect on subsequent perce... more Expectations about the magnitude of impending pain exert a substantial effect on subsequent perception. However, the neural mechanisms that underlie the predictive processes that modulate pain are poorly understood. In a combined behavioral and high-density electrophysiological study we measured anticipatory neural responses to heat stimuli to determine how predictions of pain intensity, and certainty about those predictions, modulate brain activity and subjective pain ratings. Prior to receiving randomized laser heat stimuli at different intensities (low, medium or high) subjects (n=15) viewed cues that either accurately informed them of forthcoming intensity (certain expectation) or not (uncertain expectation). Pain ratings were biased towards prior expectations of either high or low intensity. Anticipatory neural responses increased with expectations of painful vs. non-painful heat intensity, suggesting the presence of neural responses that represent predicted heat stimulus intensity. These anticipatory responses also correlated with the amplitude of the Laser-Evoked Potential (LEP) response to painful stimuli when the intensity was predictable. Source analysis (LORETA) revealed that uncertainty about expected heat intensity involves an anticipatory cortical network commonly associated with attention (left dorsolateral prefrontal, posterior cingulate and bilateral inferior parietal cortices). Relative certainty, however, involves cortical areas previously associated with semantic and prospective memory (left inferior frontal and inferior temporal cortex, and right anterior prefrontal cortex). This suggests that biasing of pain reports and LEPs by expectation involves temporally precise activity in specific cortical networks.
PAIN, 2009
Placebo has been shown to be a powerful analgesic with corresponding reduction in the activation ... more Placebo has been shown to be a powerful analgesic with corresponding reduction in the activation of the pain matrix in the brain. However it is not clear whether the placebo response is reproducible within individuals and what role personality traits might play in predicting it. We induced placebo analgesia by conditioning subjects to expect pain reduction following a sham-treatment in the guise of a local anaesthetic cream applied to one arm. Pain ratings were assessed before, during and after treatment. The procedure was repeated in a second session to assess the degree of reproducibility of the response. A high degree of correlation was found between the two sessions for the sham-treatment group (R(2) = 0.55; p < 0.001). Personality questionnaires were given during both experimental sessions to assess key traits such as optimism and state and trait anxiety. A regression model was used to statistically define a placebo responder in terms of personality scores. High dispositional optimism and low state anxiety were found to be significant predictors of placebo response. We suggest that repeated placebo responders are high in dispositional optimism and having a placebo response in the first session causes a drop in state anxiety at the beginning of the repeat session.
PAIN, 2010
The aim of mindfulness meditation is to develop present-focused, non-judgmental, attention. There... more The aim of mindfulness meditation is to develop present-focused, non-judgmental, attention. Therefore, experience in meditation should be associated with less anticipation and negative appraisal of pain. In this study we compared a group of individuals with meditation experience to a control group to test whether any differences in the affective appraisal of pain could be explained by lower anticipatory neural processing. Anticipatory and pain-evoked ERPs and reported pain unpleasantness were recorded in response to laser stimuli of matched subjective intensity between the two groups. ERP data were analysed after source estimation with LORETA. No group effects were found on the laser energies used to induce pain. More experienced meditators perceived the pain as less unpleasant relative to controls, with meditation experience correlating inversely with unpleasantness ratings. ERP source data for anticipation showed that in meditators, lower activity in midcingulate cortex relative to controls was related to the lower unpleasantness ratings, and was predicted by lifetime meditation experience. Meditators also reversed the normal positive correlation between medial prefrontal cortical activity and pain unpleasantness during anticipation. Meditation was also associated with lower activity in S2 and insula during the pain-evoked response, although the experiment could not disambiguate this activity from the preceding anticipation response. Our data is consistent with the hypothesis that meditation reduces the anticipation and negative appraisal of pain, but effects on pain-evoked activity are less clear and may originate from preceding anticipatory activity. Further work is required to directly test the causal relationship between meditation, pain anticipation, and pain experience.
PAIN, 2008
Psychological factors play a major role in exacerbating chronic pain. Effective self-management o... more Psychological factors play a major role in exacerbating chronic pain. Effective self-management of pain is often hindered by inaccurate beliefs about the nature of pain which lead to a high degree of emotional reactivity. Probabilistic models of perception state that greater confidence (certainty) in beliefs increases their influence on perception and behavior. In this study, we treat confidence as a metacognitive process dissociable from the content of belief. We hypothesized that confidence is associated with anticipatory activation of areas of the pain matrix involved with top-down modulation of pain. Healthy volunteers rated their beliefs about the emotional distress that experimental pain would cause, and separately rated their level of confidence in this belief. Confidence predicted the influence of anticipation cues on experienced pain. We measured brain activity during anticipation of pain using high-density EEG and used electromagnetic tomography to determine neural substrates of this effect. Confidence correlated with activity in right anterior insula, posterior midcingulate and inferior parietal cortices during the anticipation of pain. Activity in the right anterior insula predicted a greater influence of anticipation cues on pain perception, whereas activity in right inferior parietal cortex predicted a decreased influence of anticipatory cues. The results support probabilistic models of pain perception and suggest that confidence in beliefs is an important determinant of expectancy effects on pain perception. Ó
Pain, 2006
Experimental placebo analgesia is induced by building an expectation of reduced pain in a specifi... more Experimental placebo analgesia is induced by building an expectation of reduced pain in a specific body part, usually using an inert cream in the guise of a local anaesthetic in conjunction with conditioning. We investigated non-site-specific placebo analgesia by conditioning subjects to expect the anaesthetic cream on one arm, without specifying if they will definitely receive the cream, or to which arm it might be applied. Painful heat pulses (150 ms) from a CO2 laser were delivered randomly to both arms. A treatment group (n=24) underwent three experimental blocks (pre-cream, conditioning after cream, and post-conditioning). During the conditioning block, the intensity of the stimulus was reduced on one arm only. In the post-conditioning block it was returned to the painful level. We evaluated the change of intensity rating post-conditioning compared to the pre-cream block. In contrast to a control group (n=16), the treatment group reported a significant reduction in intensity ratings (F(1,38)=12.1; p=0.001). In the treatment group, we observed a range of placebo responses: unilateral responders (33.3%), subjects with a placebo response in the conditioned arm only; bilateral responders (33.3%), subjects reporting reduction in the intensity ratings in both arms, and non-responders, whose intensity ratings were not influenced by conditioning. We discuss these responses in terms of different levels of expected analgesia, facilitated by the absence of a site-specific focus for the treatment. We suggest this allowed the individuals suggestibility to influence their assessment of the pain experience by combining different levels of expectation with the information from the actual pain stimulus.
Neuroscience Letters, 1991
In vivo opioid receptor binding in the cortical projections of the medial (cingulate and prefront... more In vivo opioid receptor binding in the cortical projections of the medial (cingulate and prefrontal cortex) and lateral pain system (primary somatosensory cortex) in male volunteers has been quantitated using [rrC]diprenorphine and positron emission tomography. High levels of opioid receptor binding were seen in the cortical projections of the medial pain system in the cingulate and prefrontal cortex as has previously been observed in post-mortem studies. However, a focal reduction of opioid receptor binding was observed and quantitated in the primary motor/sensory strip when compared to surrounding parietal cortex. This new finding suggests that the medial pain system is likely to be more susceptible to exogenous and endogenous opioid neuromodulation than the so-called lateral pain system Neurosci. Methods, 23 (1988) 121-129.
NeuroReport, 2007
This study was designed to resolve whether experimental placebo responses are due to either incre... more This study was designed to resolve whether experimental placebo responses are due to either increased compliance or habituation. We stimulated both forearms and recorded laser-evoked potentials from 18 healthy volunteers treated on one arm with a sham analgesic cream and an inactive cream on the other (treatment group), and 13 volunteers with an inactive cream on both arms (controls). The treatment group showed a significant reduction in the pain ratings and laser-evoked potentials with both the sham and inactive creams. The control group showed no evidence of habituation to the laser stimulus. The results indicate that the reduction in pain during experimental placebo response is unlikely to be due to sensory habituation or compliance with the experimental instructions.
Neuropsychologia, 2010
Placebo has been shown to be a powerful analgesic with corresponding reduction in the activation ... more Placebo has been shown to be a powerful analgesic with corresponding reduction in the activation of the pain matrix in the brain. However, the response to placebo treatment is highly variable. It is unclear how anticipatory and pain-evoked potentials are affected by the treatment and how reproducible the response is. Laser stimulation was used to induce moderate pain in healthy volunteers. We induced placebo analgesia by conditioning subjects to expect pain reduction by applying a sham anaesthetic cream on one arm in conjunction with a reduced laser stimulus. Pain ratings were assessed before, during and after treatment. Using lectroencephalography (EEG) we measured anticipatory neural responses and pain-evoked potentials to laser heat to determine how expectation of analgesia affected the response to a placebo manipulation. This was a reproducibility study and as such the experimental procedure was repeated after a minimum gap of 2 weeks. Significant reductions in pain-evoked potentials were shown after treatment. The anticipatory responses did not change after treatment for the control and shamtreatment groups in the first session but were significantly lower in the repeat session relative to the first session in the sham-treatment group only. A significant correlation was found between the reduction in state anxiety in the repeat session relative to the first and the reduction in the anticipatory response in the sham-treatment group. Receiving a placebo treatment appears to cause a lasting change in the cognitive processing of pain for at least 6 weeks. This cognitive change may be facilitated by a change in state anxiety.
Journal of Cerebral Blood Flow & Metabolism, 1999
The binding of [11C]diprenorphine to mu, kappa, and delta subsites in cortical and subcortical st... more The binding of [11C]diprenorphine to mu, kappa, and delta subsites in cortical and subcortical structures was measured by positron emission tomography in vivo in six patients before and after surgical relief of trigeminal neuralgia pain. The volume of distribution of [11C]diprenorphine binding was significantly increased after thermocoagulation of the relevant trigeminal division in the following areas: prefrontal, insular, perigenual, mid-cingulate and inferior parietal cortices, basal ganglia, and thalamus bilaterally. In addition to the pain relief associated with the surgical procedure, there also was an improvement in anxiety and depression scores. In the context of other studies, these changes in binding most likely resulted from the change in the pain state. The results suggest an increased occupancy by endogenous opioid peptides during trigeminal pain but cannot exclude coexistent down-regulation of binding sites.
Background / Purpose: The experience of pain comprises both sensory and affective components ( Me... more Background / Purpose: The experience of pain comprises both sensory and affective components ( Melzack R &Wall PD (1965)). Selective attention to the sensory component of pain has been found to reduce the perceived intensity and affective response to pain in individuals who are anxious or fearful about pain, but increases these variables in those who are not (Brown CA and Jones AKP (2010), Hadjistavropoulos HD et al (2000)). The aim of this study was to investigate the neural correlates of this interaction between attention and anxiety.It was expected that anxiety-related neural activity in the pain matrix would be reduced by focussing attention on the sensory component of pain relative to the emotional component. Main conclusion: Attending to pain sensation reduces the relationship between anxiety and pain perception. This interaction is related to differences in cortical processing during early anticipation of pain. Specifically, attending to pain sensation reduces right Insula ac...
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2004
The accuracy of the inverse solution that finds the spatial location of the generating sources fr... more The accuracy of the inverse solution that finds the spatial location of the generating sources from averaged scalp-recorded event related potentials (ERPs) relies on assumptions about the ERP signals and the sources. We provide evidence that using independent component analysis (ICA) as a signal decomposition filter prior to applying the inverse solution reveals sources that cannot be detected by conventional source localisation methods. Five clusters of sources emerged: a single source cluster in caudal cingulate and bilateral sources in secondary somatosensory cortex (SII), inferior parietal cortex, premotor cortex and insular cortex. The locations of the source dipoles were consistent with findings using fMRI and PET but have not all been previously detected in a single electrophysiological study. In addition, the time-course of the activation of these dipoles was estimated. The results suggest that using ICA to localise single trial data is a powerful tool for exploring the spat...
Handbook of experimental pharmacology, 2014
Placebo analgesia has become a well-studied phenomenon that encompasses psychology, physiology an... more Placebo analgesia has become a well-studied phenomenon that encompasses psychology, physiology and pharmacology. In this chapter we explore the complex interactions between these disciplines in order to argue that the placebo response is more than a simple change in perception but is a cognitive style driven by prior expectations. The expectation of treatment effect is shaped by prior information and prior experience which our brain uses to predict future events. In the case of placebo analgesia the prediction of pain relief overrules the actual feeling of pain leading to a decrease in pain sensation. This altered sensation can be attributed to personality traits, altered error monitoring processes, changes in anticipatory responses to pain and activation of the endogenous opioid system. In conclusion we discuss how altered sensory processing by descending pain modulation may play a part in placebo analgesia and how the loss of the brains prefrontal regions can make it impossible to...
Current rheumatology reports, 2012
Rheumatic pain and, in particular, rheumatoid arthritis, osteoarthritis and fibromyalgia, are com... more Rheumatic pain and, in particular, rheumatoid arthritis, osteoarthritis and fibromyalgia, are common and debilitating chronic pain syndromes. Recently, human functional neuroimaging, for example EEG, fMRI, and PET has begun to reveal some of the crucial central nervous system mechanisms underlying these diseases. The purpose of this review is to summarise current knowledge on the brain mechanisms of rheumatic pain revealed by functional neuroimaging techniques. The evidence suggests that two mechanisms may be largely responsible for the clinical pain associated with these rheumatic diseases: abnormalities in the medial pain system and/or central nervous system sensitisation and inhibition. If we can understand how functioning of the central nociceptive system becomes altered, even in the absence of peripheral nociceptive input, by using functional neuroimaging techniques, in the future we may be able to develop improved, more effective treatments for patients with chronic rheumatic ...
Surface and Coatings Technology, 2000
Two new coatings based on graphite and MoS 2 have been developed. They combine low friction with ... more Two new coatings based on graphite and MoS 2 have been developed. They combine low friction with high hardness, high load capacity and exceptionally low wear. Both coatings act as solid lubricants, providing protection for both the coated surface and any opposing uncoated surface. The coatings are finding application in improving the general performance of cutting and forming tools and also make possible high-speed machining. The graphite-based coatings have exceptional wear properties under water or oil and results from wear tests under a wide range of conditions are given. A number of practical applications are given, including the protection of artificial hip joints. The advantages offered by the use of such coatings for many mechanical components are demonstrated.
PLoS ONE, 2013
The lack of clear understanding of the pathophysiology of chronic pain could explain why we curre... more The lack of clear understanding of the pathophysiology of chronic pain could explain why we currently have only a few effective treatments. Understanding how pain relief is realised during placebo analgesia could help develop improved treatments for chronic pain. Here, we tested whether experimental placebo analgesia was associated with altered resting-state cortical activity in the alpha frequency band of the electroencephalogram (EEG). Alpha oscillations have been shown to be influenced by top-down processes, which are thought to underpin the placebo response.
PAIN, 2008
Expectations about the magnitude of impending pain exert a substantial effect on subsequent perce... more Expectations about the magnitude of impending pain exert a substantial effect on subsequent perception. However, the neural mechanisms that underlie the predictive processes that modulate pain are poorly understood. In a combined behavioral and high-density electrophysiological study we measured anticipatory neural responses to heat stimuli to determine how predictions of pain intensity, and certainty about those predictions, modulate brain activity and subjective pain ratings. Prior to receiving randomized laser heat stimuli at different intensities (low, medium or high) subjects (n=15) viewed cues that either accurately informed them of forthcoming intensity (certain expectation) or not (uncertain expectation). Pain ratings were biased towards prior expectations of either high or low intensity. Anticipatory neural responses increased with expectations of painful vs. non-painful heat intensity, suggesting the presence of neural responses that represent predicted heat stimulus intensity. These anticipatory responses also correlated with the amplitude of the Laser-Evoked Potential (LEP) response to painful stimuli when the intensity was predictable. Source analysis (LORETA) revealed that uncertainty about expected heat intensity involves an anticipatory cortical network commonly associated with attention (left dorsolateral prefrontal, posterior cingulate and bilateral inferior parietal cortices). Relative certainty, however, involves cortical areas previously associated with semantic and prospective memory (left inferior frontal and inferior temporal cortex, and right anterior prefrontal cortex). This suggests that biasing of pain reports and LEPs by expectation involves temporally precise activity in specific cortical networks.
PAIN, 2009
Placebo has been shown to be a powerful analgesic with corresponding reduction in the activation ... more Placebo has been shown to be a powerful analgesic with corresponding reduction in the activation of the pain matrix in the brain. However it is not clear whether the placebo response is reproducible within individuals and what role personality traits might play in predicting it. We induced placebo analgesia by conditioning subjects to expect pain reduction following a sham-treatment in the guise of a local anaesthetic cream applied to one arm. Pain ratings were assessed before, during and after treatment. The procedure was repeated in a second session to assess the degree of reproducibility of the response. A high degree of correlation was found between the two sessions for the sham-treatment group (R(2) = 0.55; p < 0.001). Personality questionnaires were given during both experimental sessions to assess key traits such as optimism and state and trait anxiety. A regression model was used to statistically define a placebo responder in terms of personality scores. High dispositional optimism and low state anxiety were found to be significant predictors of placebo response. We suggest that repeated placebo responders are high in dispositional optimism and having a placebo response in the first session causes a drop in state anxiety at the beginning of the repeat session.
PAIN, 2010
The aim of mindfulness meditation is to develop present-focused, non-judgmental, attention. There... more The aim of mindfulness meditation is to develop present-focused, non-judgmental, attention. Therefore, experience in meditation should be associated with less anticipation and negative appraisal of pain. In this study we compared a group of individuals with meditation experience to a control group to test whether any differences in the affective appraisal of pain could be explained by lower anticipatory neural processing. Anticipatory and pain-evoked ERPs and reported pain unpleasantness were recorded in response to laser stimuli of matched subjective intensity between the two groups. ERP data were analysed after source estimation with LORETA. No group effects were found on the laser energies used to induce pain. More experienced meditators perceived the pain as less unpleasant relative to controls, with meditation experience correlating inversely with unpleasantness ratings. ERP source data for anticipation showed that in meditators, lower activity in midcingulate cortex relative to controls was related to the lower unpleasantness ratings, and was predicted by lifetime meditation experience. Meditators also reversed the normal positive correlation between medial prefrontal cortical activity and pain unpleasantness during anticipation. Meditation was also associated with lower activity in S2 and insula during the pain-evoked response, although the experiment could not disambiguate this activity from the preceding anticipation response. Our data is consistent with the hypothesis that meditation reduces the anticipation and negative appraisal of pain, but effects on pain-evoked activity are less clear and may originate from preceding anticipatory activity. Further work is required to directly test the causal relationship between meditation, pain anticipation, and pain experience.
PAIN, 2008
Psychological factors play a major role in exacerbating chronic pain. Effective self-management o... more Psychological factors play a major role in exacerbating chronic pain. Effective self-management of pain is often hindered by inaccurate beliefs about the nature of pain which lead to a high degree of emotional reactivity. Probabilistic models of perception state that greater confidence (certainty) in beliefs increases their influence on perception and behavior. In this study, we treat confidence as a metacognitive process dissociable from the content of belief. We hypothesized that confidence is associated with anticipatory activation of areas of the pain matrix involved with top-down modulation of pain. Healthy volunteers rated their beliefs about the emotional distress that experimental pain would cause, and separately rated their level of confidence in this belief. Confidence predicted the influence of anticipation cues on experienced pain. We measured brain activity during anticipation of pain using high-density EEG and used electromagnetic tomography to determine neural substrates of this effect. Confidence correlated with activity in right anterior insula, posterior midcingulate and inferior parietal cortices during the anticipation of pain. Activity in the right anterior insula predicted a greater influence of anticipation cues on pain perception, whereas activity in right inferior parietal cortex predicted a decreased influence of anticipatory cues. The results support probabilistic models of pain perception and suggest that confidence in beliefs is an important determinant of expectancy effects on pain perception. Ó
Pain, 2006
Experimental placebo analgesia is induced by building an expectation of reduced pain in a specifi... more Experimental placebo analgesia is induced by building an expectation of reduced pain in a specific body part, usually using an inert cream in the guise of a local anaesthetic in conjunction with conditioning. We investigated non-site-specific placebo analgesia by conditioning subjects to expect the anaesthetic cream on one arm, without specifying if they will definitely receive the cream, or to which arm it might be applied. Painful heat pulses (150 ms) from a CO2 laser were delivered randomly to both arms. A treatment group (n=24) underwent three experimental blocks (pre-cream, conditioning after cream, and post-conditioning). During the conditioning block, the intensity of the stimulus was reduced on one arm only. In the post-conditioning block it was returned to the painful level. We evaluated the change of intensity rating post-conditioning compared to the pre-cream block. In contrast to a control group (n=16), the treatment group reported a significant reduction in intensity ratings (F(1,38)=12.1; p=0.001). In the treatment group, we observed a range of placebo responses: unilateral responders (33.3%), subjects with a placebo response in the conditioned arm only; bilateral responders (33.3%), subjects reporting reduction in the intensity ratings in both arms, and non-responders, whose intensity ratings were not influenced by conditioning. We discuss these responses in terms of different levels of expected analgesia, facilitated by the absence of a site-specific focus for the treatment. We suggest this allowed the individuals suggestibility to influence their assessment of the pain experience by combining different levels of expectation with the information from the actual pain stimulus.
Neuroscience Letters, 1991
In vivo opioid receptor binding in the cortical projections of the medial (cingulate and prefront... more In vivo opioid receptor binding in the cortical projections of the medial (cingulate and prefrontal cortex) and lateral pain system (primary somatosensory cortex) in male volunteers has been quantitated using [rrC]diprenorphine and positron emission tomography. High levels of opioid receptor binding were seen in the cortical projections of the medial pain system in the cingulate and prefrontal cortex as has previously been observed in post-mortem studies. However, a focal reduction of opioid receptor binding was observed and quantitated in the primary motor/sensory strip when compared to surrounding parietal cortex. This new finding suggests that the medial pain system is likely to be more susceptible to exogenous and endogenous opioid neuromodulation than the so-called lateral pain system Neurosci. Methods, 23 (1988) 121-129.
NeuroReport, 2007
This study was designed to resolve whether experimental placebo responses are due to either incre... more This study was designed to resolve whether experimental placebo responses are due to either increased compliance or habituation. We stimulated both forearms and recorded laser-evoked potentials from 18 healthy volunteers treated on one arm with a sham analgesic cream and an inactive cream on the other (treatment group), and 13 volunteers with an inactive cream on both arms (controls). The treatment group showed a significant reduction in the pain ratings and laser-evoked potentials with both the sham and inactive creams. The control group showed no evidence of habituation to the laser stimulus. The results indicate that the reduction in pain during experimental placebo response is unlikely to be due to sensory habituation or compliance with the experimental instructions.
Neuropsychologia, 2010
Placebo has been shown to be a powerful analgesic with corresponding reduction in the activation ... more Placebo has been shown to be a powerful analgesic with corresponding reduction in the activation of the pain matrix in the brain. However, the response to placebo treatment is highly variable. It is unclear how anticipatory and pain-evoked potentials are affected by the treatment and how reproducible the response is. Laser stimulation was used to induce moderate pain in healthy volunteers. We induced placebo analgesia by conditioning subjects to expect pain reduction by applying a sham anaesthetic cream on one arm in conjunction with a reduced laser stimulus. Pain ratings were assessed before, during and after treatment. Using lectroencephalography (EEG) we measured anticipatory neural responses and pain-evoked potentials to laser heat to determine how expectation of analgesia affected the response to a placebo manipulation. This was a reproducibility study and as such the experimental procedure was repeated after a minimum gap of 2 weeks. Significant reductions in pain-evoked potentials were shown after treatment. The anticipatory responses did not change after treatment for the control and shamtreatment groups in the first session but were significantly lower in the repeat session relative to the first session in the sham-treatment group only. A significant correlation was found between the reduction in state anxiety in the repeat session relative to the first and the reduction in the anticipatory response in the sham-treatment group. Receiving a placebo treatment appears to cause a lasting change in the cognitive processing of pain for at least 6 weeks. This cognitive change may be facilitated by a change in state anxiety.
Journal of Cerebral Blood Flow & Metabolism, 1999
The binding of [11C]diprenorphine to mu, kappa, and delta subsites in cortical and subcortical st... more The binding of [11C]diprenorphine to mu, kappa, and delta subsites in cortical and subcortical structures was measured by positron emission tomography in vivo in six patients before and after surgical relief of trigeminal neuralgia pain. The volume of distribution of [11C]diprenorphine binding was significantly increased after thermocoagulation of the relevant trigeminal division in the following areas: prefrontal, insular, perigenual, mid-cingulate and inferior parietal cortices, basal ganglia, and thalamus bilaterally. In addition to the pain relief associated with the surgical procedure, there also was an improvement in anxiety and depression scores. In the context of other studies, these changes in binding most likely resulted from the change in the pain state. The results suggest an increased occupancy by endogenous opioid peptides during trigeminal pain but cannot exclude coexistent down-regulation of binding sites.