Pain mechanisms

Understanding pain mechanisms is the key to effective treatment. The mechanisms that have been studied, written about in science journals and discussed with patients include nociceptive pain, inflammatory pain, neuropathic pain and central sensitisation. Elucidating which are playing a role in the patient’s experience allows the doctor to prescribe the right medication and the modern physical therapist to address the issues of pain in a biopsychosocial manner. I will now clarify the latter point.

In taking a detailed history, observing patterns of movement and protection, assessing the state of the nervous system and health of the body systems, understanding behaviours and the beliefs behind them and learning of the influences upon the individual’s pain experience, one can know about the likely pain mechanisms underpinning the experience. From here the treatment strategies can be chosen to target these mechanisms. For example, top-down approaches for central sensitisation focus on the change in the properties of the central nervous system. The interventions themselves are observant of the amplification that occurs in the spinal cord and higher centres and would seek to dampen the responses with input to the brain that is perceived as normal or non-threatening. This could include sensory stimulation or movements outside of the receptive field, education to reduce fear of movement or imagery to name but a few. Inflammatory pain can also be treated with a top-down approach but local tissue based strategies would also be used. Just to note that the separation of the ‘top end’ (brain and spinal cord) from ‘bottom end’ (tissues) is really a false dichotomy as all conscious experiences are from the brain including what we see and what we feel.

Stephen McMahon and David Bennett, both experts in the field of pain science from King’s College London, produced a poster that describes these mechanisms – click here to visit the page in Nature Reviews Neuroscience. This is what they say about it:

Pain is an unpleasant sensation resulting from the intricate interplay between sensory and cognitive mechanisms. Chronic pain, resulting from disease or injury, affects nearly every fifth person in the Western world, constituting an enormous burden for the individual and society. Sensitization of pain signalling systems is a key feature of chronic pain and results in normally non-painful stimuli eliciting pain. Such sensory changes can occur not just at the sites of injury, but in surrounding normal tissues. This and other observations suggest that sensitization occurs within the CNS as well as within nociceptor terminals. Here we consider the consequences of noxious stimulus applied to our unfortunate builder’s hand, from sensory transduction to pain perception. We describe the structural and functional elements present at different levels of the nociceptive system, as well as some of the changes occurring in chronic pain states. Although our poster highlights a flow of information from the periphery to the CNS, it should be noted that higher brain centres exert both inhibitory and facilitatory controls on lower ones. The challenge for the next decade will be to effectively translate this knowledge into the development of novel analgesic agents for better pain relief.

Richmond StaceSpecialist Pain Physio Clinics, London & Surrey

Musings on pain – a book in progress (a)

I think and read about pain extensively. Not just the physiology of pain, but the whole affect upon the individual who can suffer in a multitude of ways. We have our own meaning of pain, although most people who I meet have difficulty attaching a sense of meaning to their experience. Broadly speaking, in persisting cases, the pain is deemed to be a thoroughly negative acquaintance that has hung around far too long.

The unwanted house guest, the irritating fly, the frustrating official or an enduring hammering from next door on a quiet Sunday afternoon.

Pain is an emotional and a sensory experience by definition and affected by the physical, the psychological and the social aspects of life, hence the contemporary term ‘biopsychosocial’. There are many influences, a number of which we are not even conscious of at the time. It just hurts.

Click here

Spending a great deal of time with patients,
Listening and hearing the stories of pain and suffering,
Looking and seeing the movement and behaviour changes,
The guarding and protection,
By the brain that must be revealed as the source.

I have heard some incredible histores told to me by the person sitting in front. Listening to the story from the beginning, although often they do not realise that the start point was long ago, I am piecing together the threads and connections. Some of these may seem irrelevant but are actually playing a role in the current time. Every piece of information is received and scrutinsed, nothing discarded until one is certain that there is no involvement.

The classic pain text

This book is a collection of my observations and thoughts about pain. All of these fall back on the contemporary understanding of pain that was really ignited by Pat Wall and Ron Melzack. It is no longer enough or acceptable to think about pain without considering the active role of the brain and the integrated networks of neurons within the brain that can be termed the ‘pain matrix’. However, we do not wish to be too neurocentric about pain and must wisely think about the immune system, endocrine system and autonomic nervous system within our contruct of how the body is protecting itself. For the brain’s ability to defend us is magnificent, our healing powers incredible and our ability to learn phenomenal. Together this creates opportunity, certainly in treating and understanding pain. The emotional centres (limbic system) and prefrontal cortex that are part of the pain matrix can be targeted with ‘informational therapy’ that is high quality pain education that permits deep learning about the body. Changing activity in the matrix will change pain. This does not negate the need to nourish the tissues (muscles, tendons, ligaments etc.) with movement, hands-on treatment and exercise, but we are urged by the science of pain to look beyond the tissues.

RS

CRPS & pain – some things you may not have realised

Pain is multidimensional. Pain is 100% produced by the brain in response to a perceived threat. The brain allocates a location using the cortical maps, hence why we feel pain in our backs or knees. The brain tries to make sense of the situation, scrutinising what is going on on the basis of past experience (learning) and comparing to the information being received from ALL body systems. This is the reason for the term ‘multisystem output’ as a way of describing what is happening when we are in pain.

The most obvious reason why the pain worsens is that we move, exercise or sit for too long. All of these activities are ‘physical’, asking the tissues to take the strain either rapidly or gradually. On reaching a certain level of strain, lower than normal in cases of sensitivity, nerves start sending danger signals to the spinal cord. From the spinal cord messages are relayed to the brain, still on the subject of danger. Theses are not pain signals. It is only when the brain interprets the information as threatening that the experience of pain is produced – an output from the brain. This is typical in acute situations when the injury or problem is new. The pain is vital, useful and motivates action.

A key point to understand is that the brain does not actually need the tissues to produce pain. Think about phantom limb pain. There is no limb. There are no tissues. But it hurts. It seriously hurts in may cases. So, there are other ‘triggers’ for pain besides actually moving or asking the tissues (muscles, tendons, ligaments, bones etc) to take the strain. Common ‘non-tissue’ circumstances that can amplify pain include stress, circadian rhythms, menstrual cycle, fatigue and thoughts. I think that to take this on board is an enlightening experience. To understand that your pain can be as a result of other reasons besides what you are doing physically can help to explain why it hurts at times when you have not done anything differently and you really cannot comprehend why the pain has increased.

A further influential player in our experiences is vision. I’m really interested in this as the process of ‘seeing’ is much aligned to the way pain is experienced. Information is received by the brain via the optic nerve. The brain must make sense of this data and create a credible outcome, again very much using past experience to judge the present. We still see a bird in his cage despite slender lines dividing his body (the struts of the cage). We don’t see ‘slices’ of a bird. Also consider optical illusions. A great deal of work has been done looking at the use of vision for therapeutic effect, i.e. the graded motor imagery programme. Clearly the mirror box is creating the illusion that the affected side is moving and appearing to be normal. Imagined movements requires us to ‘see’ and feel movement although we are keeping very still. The premotor cortex is very active during these imagined movements, and this part of the brain is involved in the production of pain.

From the book 'Explain Pain' by D Butler & L Moseley

What we are seeing is deemed to be an illusion in some quarters. We all have different experiences and backgrounds. Our beliefs about life and ourselves vary. This will influence what we ‘see’. If you have just watched a scary movie and then go outside into the dark to put the rubbish out, a shadow could be ‘seen’ as something more dangerous than if you have just laughed at a comedy show. Also consider when we see someone injure themselves, again on TV or watching sport. We often wince, grab our corresponding body part or take some other defensive action. Our brains are interpreting someone else’s danger and imprinting this onto our experience, perhaps as a way of helping us to learn that it is dangerous to be in their situation. This is likely due to the mirror neuron network and that when we watch someone else move or position themselves, our virtual body that exists in the brain mimics that position. There are also aspects of empathy in sharing someone’s pain. But, if that position is ‘threatening’ to our brain, we will hurt.

What do we do about that? We use strategies to desensitise and habituate, similar to dealing with any fear. The modern way of tackling pain states, especially those that persist, is using a biobehavioral approach. This means that as well as addressing tissue health with movement and treatment, we must concurrently target the brain and other systems that are involved in the pain experience, e.g. immune, endocrine. It is called ‘top-down’ – ‘bottom-up’. Top-down referring to the brain and our beliefs, understanding, thoughts, how the brain is controlling movement and protecting us; bottom-up signifying the need to nourish the tissues with movement. These exist on a spectrum and both are addressed in a contemporary biopsychosocial treatment programme – see http://www.specialistpainphysio.com/treatment

Below are some interesting abstracts in relation to this blog:

Pain. 2010 Feb;148(2):268-74. Epub 2009 Dec 11.

Pain sensation evoked by observing injury in others.

Source

School of Psychology, University of Birmingham, Edgbaston, UK.

Abstract

Observing someone else in pain produces a shared emotional experience that predominantly activates brain areas processing the emotional component of pain. Occasionally, however, sensory areas are also activated and there are anecdotal reports of people sharing both the somatic and emotional components of someone else’s pain. Here we presented a series of images or short clips depicting noxious events to a large group of normal controls. Approximately one-third of this sample reported an actual noxious somatic experience in response to one or more of the images or clips. Ten of these pain responders were subsequently recruited and matched with 10 non-responders to take part in an fMRI study. The subjects were scanned while observing static images of noxious events. In contrast with emotional images not containing noxious events the responders activated emotional and sensory brain regions associated with pain while the non-responders activated very little. These findings provide convincing evidence that some people can readily experience both the emotional and sensory components of pain during observation of other’s pain resulting in a shared physical pain experience.

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J Cogn Neurosci. 2007 Jan;19(1):42-58.

The neural substrate of human empathy: effects of perspective-taking and cognitive appraisal.

Source

INSERM Unit 280, France.

Abstract

Whether observation of distress in others leads to empathic concern and altruistic motivation, or to personal distress and egoistic motivation, seems to depend upon the capacity for self-other differentiation and cognitive appraisal. In this experiment, behavioral measures and event-related functional magnetic resonance imaging were used to investigate the effects of perspective-taking and cognitive appraisal while participants observed the facial expression of pain resulting from medical treatment. Video clips showing the faces of patients were presented either with the instruction to imagine the feelings of the patient (“imagine other”) or to imagine oneself to be in the patient’s situation (“imagine self”). Cognitive appraisal was manipulated by providing information that the medical treatment had or had not been successful. Behavioral measures demonstrated that perspective-taking and treatment effectiveness instructions affected participants’ affective responses to the observed pain. Hemodynamic changes were detected in the insular cortices, anterior medial cingulate cortex (aMCC), amygdala, and in visual areas including the fusiform gyrus. Graded responses related to the perspective-taking instructions were observed in middle insula, aMCC, medial and lateral premotor areas, and selectively in left and right parietal cortices. Treatment effectiveness resulted in signal changes in the perigenual anterior cingulate cortex, in the ventromedial orbito-frontal cortex, in the right lateral middle frontal gyrus, and in the cerebellum. These findings support the view that humans’ responses to the pain of others can be modulated by cognitive and motivational processes, which influence whether observing a conspecific in need of help will result in empathic concern, an important instigator for helping behavior.

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Hum Brain Mapp. 2009 Oct;30(10):3227-37.

Empathic neural responses to others’ pain are modulated by emotional contexts.

Source

Department of Psychology, Peking University, Beijing 100871, People’s Republic of China. shan@pku.edu.cn

Abstract

Recent brain imaging studies indicate that empathy for pain relies upon both the affective and/or the sensorimotor nodes of the pain matrix, and empathic neural responses are modulated by stimulus reality, personal experience, and affective link with others. The current work investigated whether and how empathic neural responses are modulated by emotional contexts in which painful stimulations are perceived. Using functional magnetic resonance imaging (fMRI), we first showed that perceiving a painful stimulation (needle penetration) applied to a face with neutral expression induced activation in the anterior cingulate cortex (ACC) relative to nonpainful stimulation (Q-tip touch). However, when observation of the painful stimuli delivered to a neutral face was intermixed with observation of painful or happy faces, the ACC activity decreased while the activity in the face area of the secondary somatosensory cortex increased to the painful stimulation. Moreover, the secondary somatosensory activity associated with the painful stimulation decreased when the painful stimulation was applied to faces with happy and painful expressions. The findings suggest that observing painful stimuli in an emotional context weakens affective responses but increases sensory responses to perceived pain and implies possible interactions between the affective and sensory components of the pain matrix during empathy for pain.

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Neuron. 2007 Aug 2;55(3):377-91.

The cerebral signature for pain perception and its modulation.

Source

Centre for Functional Magnetic Resonance Imaging of the Brain, Clinical Neurology and Nuffield Department of Anaesthetics, Oxford University, OX3 9DU Oxford, England, UK. irene@fmrib.ox.ac.uk

Abstract

Our understanding of the neural correlates of pain perception in humans has increased significantly since the advent of neuroimaging. Relating neural activity changes to the varied pain experiences has led to an increased awareness of how factors (e.g., cognition, emotion, context, injury) can separately influence pain perception. Tying this body of knowledge in humans to work in animal models of pain provides an opportunity to determine common features that reliably contribute to pain perception and its modulation. One key system that underpins the ability to change pain intensity is the brainstem’s descending modulatory network with its pro- and antinociceptive components. We discuss not only the latest data describing the cerebral signature of pain and its modulation in humans, but also suggest that the brainstem plays a pivotal role in gating the degree of nociceptive transmission so that the resultant pain experienced is appropriate for the particular situation of the individual.

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Neuroimage. 2009 Sep;47(3):987-94. Epub 2009 May 28.

The influence of negative emotions on pain: behavioral effects and neural mechanisms.

Source

Nuffield Department of Anaesthetics, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK. kwiech@fmrib.ox.ac.uk

Abstract

The idea that pain can lead to feelings of frustration, worry, anxiety and depression seems obvious, particularly if it is of a chronic nature. However, there is also evidence for the reverse causal relationship in which negative mood and emotion can lead to pain or exacerbate it. Here, we review findings from studies on the modulation of pain by experimentally induced mood changes and clinical mood disorders. We discuss possible neural mechanisms underlying this modulatory influence focusing on the periaqueductal grey (PAG), amygdala, anterior cingulate cortex (ACC) and anterior insula as key players in both, pain and affective processing.

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Disclaimer: this blog is for informational purposes only. If you are concerned or unsure about your pain or condition, you must consult with your GP or a health professional.

CRPS Research Update December 2012

Welcome to the December research update for CRPS and related issues:

J Med Case Reports. 2011 Aug 4;5:349.

Improvement of pain and regional osteoporotic changes in the foot and ankle by low-dose bisphosphonate therapy for complex regional pain syndrome type I: a case series.
Abe Y, Iba K, Takada J, Wada T, Yamashita T.
Source

Department of Orthopedic Surgery, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan. iba@sapmed.ac.jp.
INTRODUCTION:

Complex regional pain syndrome is characterized by pain, allodynia, hyperalgesia, edema, signs of vasomotor instability, movement disorders, joint stiffness, and regional osteopenia. It is recognized to be difficult to treat, despite various methods of treatment, including physiotherapy, calcitonin, corticosteroids, sympathetic blockade, and nonsteroidal anti-inflammatory drugs. Pathophysiologically, complex regional pain syndrome reveals enhanced regional bone resorption and high bone turnover, and so bisphosphonates, which have a potent inhibitory effect on bone resorption, were proposed for the treatment of complex regional pain syndrome.
CASE PRESENTATION:

A 48-year-old Japanese man with complex regional pain syndrome type I had severe right ankle pain with a visual analog scale score of 59 out of 100 regardless of treatment with physiotherapy and nonsteroidal anti-inflammatory drugs for five months. Radiographs showed marked regional osteoporotic changes and bone scintigraphy revealed a marked increase in radioactivity in his ankle. One month after the start of oral administration of risedronate (2.5 mg per day), his bone pain had fallen from a VAS score of 59 out of 100 to 18 out of 100. Bone scintigraphy at 12 months showed a marked reduction in radioactivity to a level comparable to that in his normal, left ankle. On the basis of these results, the treatment was discontinued at 15 months. At 32 months, our patient had almost no pain and radiographic findings revealed that the regional osteoporotic change had returned to normal.A second 48-year-old Japanese man with complex regional pain syndrome type I had severe right foot pain with a visual analog scale score of 83 out of 100 regardless of treatment with physiotherapy and nonsteroidal anti-inflammatory drugs for nine months. Radiographs showed regional osteoporotic change in his phalanges, metatarsals, and tarsals, and bone scintigraphy revealed a marked increase in radioactivity in his foot. One month after the start of oral administration of alendronate (35 mg per week), his bone pain had fallen from a visual analog scale score of 83 out of 100 to 30 out of 100 and, at nine months, was further reduced to 3 out of 100. The treatment was discontinued at 15 months because of successful pain reduction. At 30 months, our patient had no pain and the radiographic findings revealed marked improvement in regional osteoporotic changes.
CONCLUSIONS:

We believe low-dose oral administration of bisphosphonate is worth considering for the treatment of idiopathic complex regional pain syndrome type I accompanied by regional osteoporotic change.

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J Hand Surg Am. 2011 Dec 14. [Epub ahead of print]

Meta-Analysis of the Imaging Techniques for the Diagnosis of Complex Regional Pain Syndrome Type I.

Source

School of Medicine and the Division of Plastic Surgery, University of Louisville, Louisville, KY; and the Department of Orthopedics, University of Michigan, Ann Arbor, MI.

Abstract

PURPOSE:

To compare the effectiveness of imaging techniques in aiding and confirming the diagnosis of complex regional pain syndrome (CRPS) type I.

METHODS:

We conducted a meta-analysis of randomized controlled studies that evaluated the effectiveness of 3 different imaging techniques in aiding the diagnosis of CRPS type I. A systematic search in bibliographical databases resulted in 24 studies with 1,916 participants.

RESULTS:

To determine the effectiveness of each imaging technique, we determined the average specificity, sensitivity, negative predictive value, and positive predictive value and then statistically compared them using the analysis of variance statistical test, which indicated that compared with magnetic resonance imaging and plain film radiography, triple-phase bone scan had a significantly better sensitivity and negative predictive values. However, there appeared to be no statistical significance between imaging techniques when we evaluated specificity and positive predictive value using the analysis of variance test.

CONCLUSIONS:

The findings of this meta-analysis support the use of triple-phase bone scan in ruling out CRPS type I, owing to its greater sensitivity and higher negative predictive value than both magnetic resonance imaging and plain film radiography.

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J Pain. 2011 Dec 13. [Epub ahead of print]

Changes in Plasma Cytokines and Their Soluble Receptors in Complex Regional Pain Syndrome.

Source

Department of Neurology, Drexel University College of Medicine, Philadelphia, Pennsylvania.

Abstract

Complex Regional Pain Syndrome (CRPS) is a chronic and often disabling pain disorder. There is evidence demonstrating that neurogenic inflammation and activation of the immune system play a significant role in the pathophysiology of CRPS. This study evaluated the plasma levels of cytokines, chemokines, and their soluble receptors in 148 subjects afflicted with CRPS and in 60 gender- and age-matched healthy controls. Significant changes in plasma cytokines, chemokines, and their soluble receptors were found in subjects with CRPS as compared with healthy controls. For most analytes, these changes resulted from a distinct subset of the CRPS subjects. When the plasma data from the CRPS subjects was subjected to cluster analysis, it revealed 2 clusters within the CRPS population. The category identified as most important for cluster separation by the clustering algorithm was TNFα. Cluster 1 consisted of 64% of CRPS subjects and demonstrated analyte values similar to the healthy control individuals. Cluster 2 consisted of 36% of the CRPS subjects and demonstrated significantly elevated levels of most analytes and in addition, it showed that the increased plasma analyte levels in this cluster were correlated with disease duration and severity. PERSPECTIVE: The identification of biomarkers that define disease subgroups can be of great value in the design of specific therapies and of great benefit to the design of clinical trials. It may also aid in advancing our understanding of the mechanisms involved in the pathophysiology of CRPS, which may lead to novel treatments for this very severe condition.

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J Transl Med. 2011 Nov 10;9:195.

MicroRNA modulation in complex regional pain syndrome.

Source

Pharmacology & Physiology, Drexel University College of Medicine, Philadelphia, PA 19102, USA. seena.ajit@drexelmed.edu.

Abstract

ABSTRACT:

BACKGROUND:

Aberrant expression of small noncoding RNAs called microRNAs (miRNAs) is a common feature of several human diseases. The objective of the study was to identify miRNA modulation in patients with complex regional pain syndrome (CRPS) a chronic pain condition resulting from dysfunction in the central and/or peripheral nervous systems. Due to a multitude of inciting pathologies, symptoms and treatment conditions, the CRPS patient population is very heterogeneous. Our goal was to identify differentially expressed miRNAs in blood and explore their utility in patient stratification.

METHODS:

We profiled miRNAs in whole blood from 41 patients with CRPS and 20 controls using TaqMan low density array cards. Since neurogenic inflammation is known to play a significant role in CRPS we measured inflammatory markers including chemokines, cytokines, and their soluble receptors in blood from the same individuals. Correlation analyses were performed for miRNAs, inflammatory markers and other parameters including disease symptoms, medication, and comorbid conditions.

RESULTS:

Three different groups emerged from miRNA profiling. One group was comprised of 60% of CRPS patients and contained no control subjects. miRNA profiles from the remaining patients were interspersed among control samples in the other two groups. We identified differential expression of 18 miRNAs in CRPS patients. Analysis of inflammatory markers showed that vascular endothelial growth factor (VEGF), interleukin1 receptor antagonist (IL1Ra) and monocyte chemotactic protein-1 (MCP1) were significantly elevated in CRPS patients. VEGF and IL1Ra showed significant correlation with the patients reported pain levels. Analysis of the patients who were clustered according to their miRNA profile revealed correlations that were not significant in the total patient population. Correlation analysis of miRNAs detected in blood with additional parameters identified miRNAs associated with comorbidities such as headache, thyroid disorder and use of narcotics and antiepileptic drugs.

CONCLUSIONS:

miRNA profiles can be useful in patient stratification and have utility as potential biomarkers for pain. Differentially expressed miRNAs can provide molecular insights into gene regulation and could lead to new therapeutic intervention strategies for CRPS.

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Pain. 2011 Dec 9. [Epub ahead of print]

Sensory signs in complex regional pain syndrome and peripheral nerve injury.

Source

Division of Neurological Pain Research and Therapy, Department of Neurology, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany.

Abstract

This study determined patterns of sensory signs in complex regional pain syndrome (CRPS) type I and II and peripheral nerve injury (PNI). Patients with upper-limb CRPS-I (n=298), CRPS-II (n=46), and PNI (n=72) were examined with quantitative sensory testing according to the protocol of the German Research Network on Neuropathic Pain. The majority of patients (66%-69%) exhibited a combination of sensory loss and gain. Patients with CRPS-I had more sensory gain (heat and pressure pain) and less sensory loss than patients with PNI (thermal and mechanical detection, hypoalgesia to heat or pinprick). CRPS-II patients shared features of CRPS-I and PNI. CRPS-I and CRPS-II had almost identical somatosensory profiles, with the exception of a stronger loss of mechanical detection in CRPS-II. In CRPS-I and -II, cold hyperalgesia/allodynia (28%-31%) and dynamic mechanical allodynia (24%-28%) were less frequent than heat or pressure hyperalgesia (36%-44%, 67%-73%), and mechanical hypoesthesia (31%-55%) was more frequent than thermal hypoesthesia (30%-44%). About 82% of PNI patients had at least one type of sensory gain. QST demonstrates more sensory loss in CRPS-I than hitherto considered, suggesting either minimal nerve injury or central inhibition. Sensory profiles suggest that CRPS-I and CRPS-II may represent one disease continuum. However, in contrast to recent suggestions, small fiber deficits were less frequent than large fiber deficits. Sensory gain is highly prevalent in PNI, indicating a better similarity of animal models to human patients than previously thought. These sensory profiles should help prioritize approaches for translation between animal and human research.

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Anesthesiology. 2011 Dec 2. [Epub ahead of print]

Predictors of Pain Relieving Response to Sympathetic Blockade in Complex Regional Pain Syndrome Type 1.

Source

* Consultant Anesthesiologist, Department of Anesthesiology and Pain Management, St. Elisabeth Hospital, Tilburg, The Netherlands. † Research Associate, ‡ Professor, Department of Anesthesiology and Pain Medicine, § Associate Professor, Department of Neurology, Maastricht University Medical Centre, Maastricht, The Netherlands. ‖ Associate Professor, Department of Anesthesiology and Institute for Health and Care Research, VU University Medical Centre, Amsterdam, The Netherlands. # Biostatistician, Epidemiologist, Department of Clinical Epidemiology and Medical Technology Assessment, University Hospital Maastricht, Maastricht, The Netherlands. ** Consultant Anesthesiologist, Department of Anesthesiology and Multidisciplinary Pain Centre, Hospital Oost-Limburg, Genk, Belgium.

Abstract

BACKGROUND:

Sympathetic blockade with local anesthetics is used frequently in the management of complex regional pain syndrome type 1(CRPS-1), with variable degrees of success in pain relief. The current study investigated which signs or symptoms of CRPS-1 could be predictive of outcome. The incidence of side effects and complications of sympathetic blockade also were determined prospectively.

METHODS:

A prospective observational study was done of 49 patients with CRPS-1 in one extremity only and for less than 1-yr duration who had severe pain and persistent functional impairment with no response to standard treatment with medication and physical therapy.

RESULTS:

Fifteen (31%) patients had good or moderate response. The response rate was not different in patient groups with cold or warm type CRPS-1 or in those with more or less than 1.5°C differential increase in skin temperature after sympathetic blockade. Allodynia and hypoesthesia were negative predictors for treatment success in CRPS-1. There were no symptoms or signs of CRPS-1 that positively predicted treatment success. A majority of patients (84%) experienced transient side effects such as headache, dysphagia, increased pain, backache, nausea, blurred vision, groin pain, hoarseness, and hematoma at the puncture site. No major complications were reported.

CONCLUSIONS:

The presence of allodynia and hypoesthesia are negative predictors for treatment success. The selection of sympathetic blockade as treatment for CRPS-1 should be balanced carefully between potential success and side effect ratio. The procedure is as likely to cause a transient increase in pain as a decrease in pain. Patients should be informed accordingly.

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CNS Drugs. 2011 Dec 1. doi: 10.2165/11595200-000000000-00000. [Epub ahead of print]

Efficacy and Safety of Ketamine in Patients with Complex Regional Pain Syndrome: A Systematic Review.

Source

Department of Anesthesiology, Division of Pain Management, Duke University School of Medicine, Durham, NC, USA.

Abstract

Despite being a recognized clinical entity for over 140 years, complex regional pain syndrome (CRPS) remains a difficult-to-treat condition. While there have been multiple therapies explored in the treatment of CRPS, NMDA antagonists such as ketamine continue to hold significant interest because of their potential ability to alter the central sensitization noted in chronic pain states. The objective of this review is to identify published literature for evidence of the efficacy and safety of ketamine in the treatment of CRPS. PubMed and the Cochrane Controlled Trials Register were searched (final search 26 May 2011) using the MeSH terms ‘ketamine’, ‘complex regional pain syndrome’, ‘analgesia’ and ‘pain’ in the English literature. The manuscript bibliographies were then reviewed to identify additional relevant papers. Observational trials were evaluated using the Agency for Healthcare Research and Quality criteria; randomized trials were evaluated using the methodological assessment of randomized clinical trials. The search methodology yielded three randomized, placebo-controlled trials, seven observational studies and nine case studies/reports. In aggregate, the data available reveal ketamine as a promising treatment for CRPS. The optimum dose, route and timing of administration remain to be determined. Randomized controlled trials are needed to establish the efficacy and safety of ketamine and to determine its long-term benefit in CRPS.

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Disclaimer

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about CRPS should consult with a qualified healthcare professional.

 

Mindfulness

Mindfulness has grown in popularity over recent years, and for good reason. Those who regularly practice mindful meditation and mindfulness on a day-to-day basis will tell you about their clarity of thought, their sense of ease and their good physical health. The practice is recommended by NICE for depression as well as the frequent teaching of mindfulness as a way to deal with pain.

At the clinic, I encourage mindful practice to help the individual be released from the pull of negative and unhelpful thinking about pain. We all have thoughts. This is the action of the mind and is a normal process. Automatic thoughts pop into our head and trigger emotional and physical responses–think about a waxy, yellow lemon resting upon a plate; you take a knife and cut into the rind, releasing the citrus odour as you divide the lemon in two, the pieces rolling away from the blade; you further cut the two halves into quarter segments, each time triggering a small burst of juice into the air around; imagine taking one segment and gently placing it into the front of your mouth; what are you experiencing? Thoughts change our physiology because our brains respond to thinking or imagining, just as if we are present. This is why it can hurt when we watch someone else move their body in a way that would be painful for us.


Automatic thoughts are just that. How we respond next we can decide. By being observant of our thoughts we can avoid following an automatic thought with another thought and another that lead to persisting physiological responses and emotions that are unpleasant and unhelpful. In particular those thougths that often recur and create unease and anxiety. They are simply thoughts. They are not us and they are not reality. They are just thoughts. But, they can be powerful unless we can find a way to be observant, non-judgmental, aware and present. That ‘way’ can be mindfulness.

Here are some great people talking about mindfulness and meditation

 

There has been and continues to be a great deal of work looking at mindfulness and how it may work. The Oxford Mindfulness Centre (OMC) undertakes research and provides training.
‘The OMC Team does ground-breaking clinical and neuroscience research on mindfulness. It assesses the efficacy of different forms of mindfulness practice for different types of problem, and is building up a peer-reviewed body of knowledge about what forms of mindfulness intervention best suits which type of person.’
A list of the OMC publications is available here
For further information on our use of mindfulness for pain, please email richmond@specialistpainphysio.com

Imagery & mirrors

Many readers will know about mirror box therapy for CRPS and other painful conditions. The Graded Motor Imagery Programme that we use at Specialist Pain Physio is sequential training that starts with laterality, progressing to imagined movements and then to mirror therapy. There is some really good data for the programme and CRPS but it can also be effective with other chronic pains. Interestingly we are now seeing components of GMI being used and written about in the popular press, most recently for Parkinson’s disease and arthritis.

Brain training for pain

A brief article in New Scientist describes the Parkinson’s research by David Linden at Cardiff University. 10 subjects were asked to think about movement for 45 minutes whilst they were having brain scans. Five of the subjects were given feedback that showed them how they were activating the brain and all were asked to practice the imagery at home. Two months later rigidity and tremor had reduced some 37% in the feedback group. The thinking is that there is cortical change underpinning this improved function that is feasible.

Mirror therapy for pain

At The Society for Neuroscience annual meeting 2011 a small study was performed with arthritis (OA & RA) patients used mirror therapy. Subjects observed the moving reflection of the researcher’s hand in the mirror whilst producing the same movement themselves with their hidden hand. After 1 minute it was noted that the subjects pain improved. This was reported in The Guardian today.

For details on our treatment programmes including imagery, mirror therapy, graded motor imagery and other neuroscience-based techniques, come and see our website at http://www.specialistpainphysio.com or call 07518 445491. Our clinics are based in London and Surrey http://www.specialistpainphysio.com/clinics

CRPS, Pain and Brain Research update November Part 1

Welcome to the first November research update.

Specialist Pain Physio Clinics, London

J Pain 2011 Oct 25. [Epub ahead of print]

Pain-Related Fear, Perceived Harmfulness of Activities, and Functional Limitations in Complex Regional Pain Syndrome Type I.

Source

Department of Rehabilitation, University Hospital Maastricht, Maastricht, The Netherlands; Department Clinical Psychological Science, Maastricht University, Maastricht, The Netherlands.

Abstract

Numerous studies have shown that pain-related fear is one of the strongest predictors of pain disability in patients with chronic musculoskeletal pain, and there is evidence that the reduction of pain-related fear through an exposure treatment can be associated with restoration of functional abilities in patients with complex regional pain syndrome type I (CRPS-I). These findings suggest that pain-related fear may be associated with functional limitations in neuropathic pain as well. The aim of the current study was to test whether the debilitating role of pain-related fear generalizes to patients with CRPS-I. The results of 2 studies are presented. Study I includes a sample of patients with early CRPS-I referred to an outpatient pain clinic. In Study II, patients with chronic CRPS who are members of a patients’ association were invited to participate. The results show that in early CRPS-I, pain severity but not fear of movement/(re)injury as measured with the Tampa Scale for Kinesiophobia was related to functional limitations. In patients with chronic CRPS-I, however, perceived harmfulness of activities as measured with the pictorial assessment method significantly predicted functional limitations beyond and above the contribution of pain severity. Not fear of movement/(re)injury in general, but the perceived harmfulness of activities appears a key factor that might be addressed more systematically in the clinical assessment of patients with CRPS-I. These results support the idea that pain-related fear might be a promising concept in the understanding of pain disability in patients with neuropathic pain. PERSPECTIVE: This is the first study showing that perceived harmfulness of activities contribute to the functional limitations in CRPS-I. The current findings may help clinicians customizing cognitive-behavioral treatments for patients with chronic neuropathic pain.

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Clin J Pain. 2011 Oct 13. [Epub ahead of print]

Effect of Immunomodulating Medications in Complex Regional Pain Syndrome: A Systematic Review.

Source

Erasmus MC, Rotterdam, The Netherlands.

Abstract

BACKGROUND:

Different mechanisms are involved in a complex network of interactions resulting in the painful and impairing disorder, complex regional pain syndrome (CRPS). There is convincing evidence that inflammation plays a pivotal role in the pathophysiology of CRPS. Immunomodulating medication reduces the manifestation of inflammation by acting on the mediators of inflammation. Therefore, as inflammation is involved in the pathophysiology of CRPS, immunomodulating medication in CRPS patients may prove beneficial.

OBJECTIVES:

To describe the current empirical evidence for the efficacy of administering the most commonly used immunomodulating medication (ie, glucocorticoids, tumor necrosis factor-α antagonists, thalidomide, bisphosphonates, and immunoglobulins) in CRPS patients.

METHODS:

PubMed was searched for original articles that investigated CRPS and the use of one of the abovementioned immunomodulating agents.

RESULTS:

The search yielded 39 relevant articles: from these, information on study design, sample size, duration of disease, type and route of medication, primary outcome measures, and results was examined.

DISCUSSION:

Theoretically, the use of immunomodulating medication could counteract the ongoing inflammation and might be an important step in improving a disabled hand or foot, leading to further recovery. However, more high-quality intervention studies are needed.

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PLoS One. 2011;6(10):e26010. Epub 2011 Oct 13. Click here for article

Brain morphological signatures for chronic pain.

Source

Department of Physiology, Northwestern University, Chicago, Illinois, United States of America.

Abstract

Chronic pain can be understood not only as an altered functional state, but also as a consequence of neuronal plasticity. Here we use in vivo structural MRI to compare global, local, and architectural changes in gray matter properties in patients suffering from chronic back pain (CBP), complex regional pain syndrome (CRPS) and knee osteoarthritis (OA), relative to healthy controls. We find that different chronic pain types exhibit unique anatomical ‘brain signatures’. Only the CBP group showed altered whole-brain gray matter volume, while regional gray matter density was distinct for each group. Voxel-wise comparison of gray matter density showed that the impact on the extent of chronicity of pain was localized to a common set of regions across all conditions. When gray matter density was examined for large regions approximating Brodmann areas, it exhibited unique large-scale distributed networks for each group. We derived a barcode, summarized by a single index of within-subject co-variation of gray matter density, which enabled classification of individual brains to their conditions with high accuracy. This index also enabled calculating time constants and asymptotic amplitudes for an exponential increase in brain re-organization with pain chronicity, and showed that brain reorganization with pain chronicity was 6 times slower and twice as large in CBP in comparison to CRPS. The results show an exuberance of brain anatomical reorganization peculiar to each condition and as such reflecting the unique maladaptive physiology of different types of chronic pain.

Research Update: CRPS and the Immune system

Comment

Our understanding of the role of the immune system and pain has moved forwards enormously. The way in which the immune system affects sensitivity needs to be considered when designing a treatment programme. Thinking about ‘neuroimmune’ responses to movement, exercise, physical therapy and thoughts about the pain or movement (click here for an interesting study) is the contemporary way of reasoning how the body is dealing with the perceived threat.

The immune system: ‘dealing with healing’, protecting us and learning.

Immnue system and inflammation

Pain 2011 Aug 2. [Epub ahead of print]

Autoimmunity against the β(2) adrenergic receptor and muscarinic-2 receptor in complex regional pain syndrome.

Source

Department of Neurology, Justus-Liebig-University, Giessen, Germany.

Abstract

Complex regional pain syndrome (CRPS) is a painful condition affecting one or more extremities of the body, marked by a wide variety of symptoms and signs that are often difficult to manage because the pathophysiology is incompletely understood. Thus, diverse treatments might be ineffective. A recent report revealed the presence of autoantibodies against differentiated autonomic neurons in CRPS patients. However, it remained unclear how the antibodies act in the development of CRPS. We therefore aimed to characterize these antibodies and identify target antigens. Functional properties of affinity-purified immunoglobulin G of control subjects or CRPS patients were assessed using a cardiomyocyte bioassay. Putative corresponding receptors were identified using antagonistic drugs, and synthesized peptide sequences corresponding to segments of these receptors were used to identify the target epitopes. Chinese hamster ovary cells were transfected with putative receptors to ensure observed binding. Further, changes in the intracellular Ca(2+) concentration induced by agonistic immunoglobulin G were measured using the Ca(2+)-sensitive fluorescent dye fura-2 assay. Herein, we demonstrate the presence of autoantibodies in a subset of CRPS patients with agonistic-like properties on the β(2) adrenergic receptor and/or the muscarinic-2 receptor. We identified these autoantibodies as immunoglobulin G directed against peptide sequences from the second extracellular loop of these receptors. The identification of functionally active autoantibodies in serum samples from CRPS patients supports an autoimmune pathogenesis of CRPS. Thus, our findings contribute to the further understanding of this disease, could help in the diagnosis in future, and encourage new treatment strategies focusing on the immune system

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Ann N Y Acad Sci. 2007 Jun;1107:168-73.

Autoimmunity in complex-regional pain syndrome.

Source

Department of Neurology, Justus-Liebig-University, Giessen, Germany. franz.blaes@neuro.med.uni-giessen.de

Abstract

Complex regional pain syndrome (CRPS) is an etiologically unclear syndrome with the main symptoms being pain, trophic and autonomic disturbances, and functional impairment that develops after limb trauma or operation and is located at the distal site of the affected limb. Because autoantibodies against nervous system structures have been described in these patients, an autoimmune etiology of CRPS is discussed. These autoantibodies bind to the surface of peripheral autonomic neurons. Using a competitive binding assay, it can be shown that at least some of the CRPS sera bind to the same neuronal epitope. Autoimmune etiology of CRPS is a new pathophysiological concept and may have severe impact on the treatment of this often chronic disease.

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Pain. 2009 Jun;143(3):246-51. Epub 2009 Apr 16.

Autoantibodies in complex regional pain syndrome bind to a differentiation-dependent neuronal surface autoantigen.

Source

Dept. of Neurology, Justus-Liebig-University, Am Steg 14, 35392 Giessen, Germany.

Abstract

Complex regional pain syndrome, which is characterised by pain and trophic disturbances, develops frequently after peripheral limb trauma. There is an increasing evidence of an involvement of the immune system in CRPS, and recently we showed that CRPS patients have autoantibodies against nervous system structures. Therefore we tested the sera of CRPS patients, neuropathy patients and healthy volunteers for surface-binding autoantibodies to primary cultures of autonomic neurons and differentiated neuroblastoma cell lines using flow cytometry. Thirteen of 30 CRPS patients, but none of 30 healthy controls and only one of the 20 neuropathy sera had specific surface binding to autonomic neurons (p<0.001). The majority of the sera reacted with both sympathetic and myenteric plexus neurons. Interestingly, 6/30 CRPS sera showed binding to undifferentiated SH-SY5Y neuroblastoma cells. However, differentiation of SH-SY5Y into a cholinergic phenotype induced a surface antigen, which is recognised by 60% of CRPS sera (18/30), but not by controls (p<0.001). Our data show that about 30-40% of CRPS patients have surface-binding autoantibodies against an inducible autonomic nervous system autoantigen. These data support an autoimmune hypothesis in CRPS patients. Further studies must elucidate origin and function of these autoantibodies in CRPS.

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Clin Exp Immunol. 2011 Apr;164(1):108-17. doi: 10.1111/j.1365-2249.2010.04308.x. Epub 2011 Feb 8.

Elevated blood levels of inflammatory monocytes (CD14+ CD16+ ) in patients with complex regional pain syndrome.

Abstract

Complex regional pain syndrome (CRPS) is a chronic pain disorder. Although its pathophysiology is not completely understood, neurogenic inflammation is thought to play a significant role. Microglia and astrocytes are activated following tissue injury or inflammation and have been reported to be both necessary and sufficient for enhanced nociception. Blood-borne monocytes/macrophages can infiltrate the central nervous system (CNS) and differentiate into microglia resulting in hypersensitivity and chronic pain. The primary aim of this study was to evaluate the proportion of the proinflammatory CD14(+) CD16(+) monocytes as well as plasma cytokine levels in blood from CRPS patients compared to age- and gender-matched healthy control individuals. Forty-six subjects (25 CRPS, 21 controls) were recruited for this study. The percentage of monocytes, T, B or natural killer (NK) cells did not differ between CRPS and controls. However, the percentage of the CD14(+) CD16(+) monocyte/macrophage subgroup was elevated significantly (P<0·01) in CRPS compared to controls. Individuals with high percentage of CD14(+) CD16(+) demonstrated significantly lower (P<0·05) plasma levels on the anti-inflammatory cytokine interleukin (IL)-10. Our data cannot determine whether CD14(+) CD16(+) monocytes became elevated prior to or after developing CRPS. In either case, the elevation of blood proinflammatoty monocytes prior to the initiating event may predispose individuals for developing the syndrome whereas the elevation of blood proinflammatory monocytes following the development of CRPS may be relevant for its maintenance. Further evaluation of the role the immune system plays in the pathogenesis of CRPS may aid in elucidating disease mechanisms as well as the development of novel therapies for its treatment.

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J Clin Immunol. 2010 May;30 Suppl 1:S103-8.

Immunoglobulin responsive chronic pain.

Source

Pain Research Institute, 3rd Floor, Clinical Sciences Centre, Liverpool University, Liverpool, UK. andreasgoebel@rocketmail.com

Abstract

INTRODUCTION:

Over the last 15 years, clinical and experimental data have emerged that suggest that peripheral and central, glial-mediated neuroimmune activation is both necessary and sufficient to sustain chronic pain. Immune modulation appears to be, therefore, a possible new therapeutic option.

MATERIALS AND METHODS:

The Medline database and international trial registry databases were searched using the keywords “intravenous immunoglobulin” or “IVIG,” “pain” or “chronic pain,” “neuropathic pain,” “CRPS,” “complex regional pain syndrome” or “fibromyalgia.”

RESULTS:

Evidence from RCTs suggest that IVIG is effective to reduce pain in complex regional pain syndrome (low-dose IVIG) and post-polio syndrome (high-dose IVIG), and open trials have suggested efficacy in additional pain conditions.

CONCLUSION:

IVIG therapy may emerge as a novel treatment modality for refractory cases. However, before this drug can be confidently used by clinicians, important questions need to be answered concerning optimal treatment doses, duration of treatment, and its effect on function and quality of life.

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Ann Intern Med. 2010 Feb 2;152(3):152-8.

Intravenous immunoglobulin treatment of the complex regional pain syndrome: a randomized trial.

Abstract

BACKGROUND:

Treatment of long-standing complex regional pain syndrome (CRPS) is empirical and often of limited efficacy. Preliminary data suggest that the immune system is involved in sustaining this condition and that treatment with low-dose intravenous immunoglobulin (IVIG) may substantially reduce pain in some patients.

OBJECTIVE:

To evaluate the efficacy of IVIG in patients with longstanding CRPS under randomized, controlled conditions.

DESIGN:

A randomized, double-blind, placebo-controlled crossover trial. (National Research Registry number: N0263177713; International Standard Randomised Controlled Trial Number Registry: 63918259)

SETTING:

University College London Hospitals Pain Management Centre.

PATIENTS:

Persons who had pain intensity greater than 4 on an 11-point (0 to 10) numerical rating scale and had CRPS for 6 to 30 months that was refractory to standard treatment.

INTERVENTION:

IVIG, 0.5 g/kg, and normal saline in separate treatments, divided by a washout period of at least 28 days.

MEASUREMENTS:

The primary outcome was pain intensity 6 to 19 days after the initial treatment and the crossover treatment.

RESULTS:

13 eligible participants were randomly assigned between November 2005 and May 2008; 12 completed the trial. The average pain intensity was 1.55 units lower after IVIG treatment than after saline (95% CI, 1.29 to 1.82; P < 0.001). In 3 patients, pain intensity after IVIG was less than after saline by 50% or more. No serious adverse reactions were reported.

LIMITATION:

The trial was small, and recruitment bias and chance variation could have influenced results and their interpretation.

CONCLUSION:

IVIG, 0.5 g/kg, can reduce pain in refractory CRPS. Studies are required to determine the best immunoglobulin dose, the duration of effect, and when repeated treatments are needed.

Body ownership

Here are a few papers looking at this fascinating a relevant area. Our sense of self is clearly affected in many pain states and in other situations when we are under threat. This is an area we address fully as part of our rehabilitation and treatment programmes for CRPS, other chronic pain states and injuries. The loss of a sense of self is underpinned by a range of physiological changes throughout the nervous system and must be re-trained for normal functioning.

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Curr Opin Anaesthesiol. 2011 Oct;24(5):524-31.

Phantom limb pain and bodily awareness: current concepts and future directions.

Source

aExperimental Neuropsychology Research Unit, Monash University, Clayton, Victoria bSansom Institute for Health Research, University of South Australia, Adelaide, South Australia cNeuroscience Research Australia, Randwick, New South Wales, Australia.

Abstract

PURPOSE OF REVIEW:

Phantom pain is a frequent consequence of amputation or deafferentation. There are many possible contributing mechanisms, including stump-related pathology, spinal and cortical changes. Phantom limb pain is notoriously difficult to treat. Continued consideration of the factors associated with phantom pain and its treatment is of utmost importance, not only to advance the scientific knowledge about the experience of the body and neuropathic pain, but also fundamentally to promote efficacious pain management.

RECENT FINDINGS:

This review first discusses the mechanisms associated with phantom pain and summarizes the current treatments. The mechanisms underlying phantom pain primarily relate to peripheral/spinal dysfunction, and supraspinal and central plasticity in sensorimotor body representations. The most promising methods for managing phantom pain address the maladaptive changes at multiple levels of the neuraxis, for example, complementing pharmacological administration with physical, psychological or behavioural intervention. These supplementary techniques are even efficacious in isolation, perhaps by replacing the absent afferent signals from the amputated limb, thereby restoring disrupted bodily representations.

SUMMARY:

Ultimately, for optimal patient outcomes, treatments should be both symptom and mechanism targeted.

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J Physiol. 2011 Jun 15;589(Pt 12):3009-21. Epub 2011 Apr 26.

Proprioceptive signals contribute to the sense of body ownership.

Source

Neuroscience Research Australia, Barker Street, Randwick, Sydney, NSW 2031, Australia.

Abstract

The sense of body ownership, knowledge that parts of our body ‘belong’ to us, is presumably developed using sensory information. Cutaneous signals seem ideal for this and can modify the sense of ownership. For example, an illusion of ownership over an artificial rubber hand can be induced by synchronously stroking both the subject’s hidden hand and a visible artificial hand. Like cutaneous signals, proprioceptive signals (e.g. frommuscle receptors) exclusively signal events occurring in the body, but the influence of proprioceptors on the sense of body ownership is not known. We developed a technique to generate an illusion of ownership over an artificial plastic finger, using movement at the proximal interphalangeal joint as the stimulus. We then examined this illusion in 20 subjects when their index finger was intact and when the cutaneous and joint afferents from the finger had been blocked by local anaesthesia of the digital nerves. Subjects still experienced an illusion of ownership, induced by movement, over the plastic finger when the digital nerves were blocked. This shows that local cutaneous signals are not essential for the illusion and that inputs arising proximally, presumably from receptors in muscles which move the finger, can influence the sense of body ownership. Contrary to other studies, we found no evidence that voluntary movements induce stronger illusions of body ownership than those induced by passive movement. It seems that the congruence of sensory stimuli ismore important to establish body ownership than the presence of multiple sensory signals.

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Neuropsychologia. 2010 Feb;48(3):713-25. Epub 2009 Nov 11.

Crossmodal congruency measures of lateral distance effects on the rubber hand illusion.

Source

Macquarie Centre for Cognitive Science, Macquarie University, Sydney, NSW 2109, Australia. regine.zopf@maccs.mq.edu.au

Abstract

Body ownership for an artificial hand and the perceived position of one’s own hand can be manipulated in the so-called rubber hand illusion. To induce this illusion, typically an artificial hand is placed next to the participant’s body and stroked in synchrony with the real hand, which is hidden from view. Our first aim was to test if the crossmodal congruency task could be used to obtain a measure for the strength of body ownership in the rubber hand illusion. In this speeded location discrimination task participants responded to tactile targets presented to their index or middle finger, while trying to ignore irrelevant visual distracters placed on the artificial hand either on the congruent finger or on the incongruent finger. The difference between performance on congruent and incongruent trials (crossmodal congruency effect, CCE) indicates the amount of multisensory interactions between tactile targets and visual distracters. In order to investigate if changes in body ownership influence the CCE, we manipulated ownership for an artificial hand by synchronous and asynchronous stroking before the crossmodal congruency task (blocked design) in Experiment 1 and during the crossmodal congruency task (interleaved trial-by-trial design) in Experiment 2. Modulations of the CCE by ownership for an artificial hand were apparent in the interleaved trial-by-trial design. These findings suggest that the CCE can be used as an objective measure for body ownership. Secondly, we tested the hypothesis that the lateral spatial distance between the real hand and artificial hand limits the rubber hand illusion. We found no lateral spatial limits for the rubber hand illusion created by synchronous stroking within reaching distances. In conclusion, the sense of ownership seems to be related to modulations of multisensory interactions possibly through peripersonal space mechanisms, and these modulations do not appear to be limited by an increase in distance between artificial hand and real hand.

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Neuropsychologia. 2010 Feb;48(3):703-12. Epub 2009 Oct 9.

My body in the brain: a neurocognitive model of body-ownership.

Source

Department of Psychology, Royal Holloway, University of London, Egham, Surrey, UK. manos.tsakiris@rhul.ac.uk

Abstract

Empirical research on the bodily self has only recently started to investigate how the link between a body and the experience of this body as mine is developed, maintained or disturbed. The Rubber Hand Illusion has been used as a model instance of the normal sense of embodiment to investigate the processes that underpin the experience of body-ownership. This review puts forward a neurocognitive model according to which body-ownership arises as an interaction between current multisensory input and internal models of the body. First, a pre-existing stored model of the body distinguishes between objects that may or may not be part of one’s body. Second, on-line anatomical and postural representations of the body modulate the integration of multisensory information that leads to the recalibration of visual and tactile coordinate systems. Third, the resulting referral of tactile sensation will give rise to the subjective experience of body-ownership. These processes involve a neural network comprised of the right temporoparietal junction which tests the incorporeability of the external object, the secondary somatosensory cortex which maintains an on-line representation of the body, the posterior parietal and ventral premotor cortices which code for the recalibration of the hand-centred coordinate systems, and the right posterior insula which underpins the subjective experience of body-ownership. The experience of body-ownership may represent a critical component of self-specificity as evidenced by the different ways in which multisensory integration in interaction with internal models of the body can actually manipulate important physical and psychological aspects of the self.

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Cereb Cortex. 2007 Oct;17(10):2235-44. Epub 2006 Nov 30.

Neural signatures of body ownership: a sensory network for bodily self-consciousness.

Source

Wellcome Department of Imaging Neuroscience, Institute of Neurology, University College London, London, UK. e.tsakiris@ucl.ac.uk

Abstract

Body ownership refers to the special perceptual status of one’s own body, which makes bodily sensations seem unique to oneself. We studied the neural correlates of body ownership by controlling whether an external object was accepted as part of the body or not. In the rubber hand illusion (RHI), correlated visuotactile stimulation causes a fake hand to be perceived as part of one’s own body. In the present study, we distinguished between the causes (i.e., multisensory stimulation) and the effect (i.e., the feeling of ownership) of the RHI. Participants watched a right or a left rubber hand being touched either synchronously or asynchronously with respect to their own unseen right hand. A quantifiable correlate of the RHI is a shift in the perceived position of the subject’s hand toward the rubber hand. We used positron emission tomography to identify brain areas whose activity correlated with this proprioceptive measure of body ownership. Body ownership was related to activity in the right posterior insula and the right frontal operculum. Conversely, when the rubber hand was not attributed to the self, activity was observed in the contralateral parietal cortex, particularly the somatosensory cortex. These structures form a network that plays a fundamental role in linking current sensory stimuli to one’s own body and thus also in self-consciousness.

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Ann N Y Acad Sci. 2011 Apr;1225:72-82. doi: 10.1111/j.1749-6632.2011.05990.x.

Significance of the insula for the evolution of human awareness of feelings from the body.

Source

Atkinson Research Laboratory, Barrow Neurological Institute, Phoenix, Arizona, USA. bcraig@chw.edu

Abstract

An ascending sensory pathway that underlies feelings from the body, such as cooling or toothache, terminates in the posterior insula. Considerable evidence suggests that this activity is rerepresented and integrated first in the mid-insula and then in the anterior insula. Activation in the anterior insula correlates directly with subjective feelings from the body and, strikingly, with all emotional feelings. These findings appear to signify a posterior-to-anterior sequence of increasingly homeostatically efficient representations that integrate all salient neural activity, culminating in network nodes in the right and left anterior insulae that may be organized asymmetrically in an opponent fashion. The anterior insula has appropriate characteristics to support the proposal that it engenders a cinemascopic model of human awareness and subjectivity. This review presents the author’s views regarding the principles of organization of this system and discusses a possible sequence for its evolution, as well as particular issues of historical interest.

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Brain Struct Funct. 2010 Jun;214(5-6):563-77. Epub 2010 May 29.

The sentient self.

Source

Atkinson Research Laboratory, Barrow Neurological Institute, 350 West Thomas Rd., Phoenix, AZ 85013, USA. bcraig@chw.edu

Abstract

This article addresses the neuroanatomical evidence for a progression of integrative representations of affective feelings from the body that lead to an ultimate representation of all feelings in the bilateral anterior insulae, or “the sentient self.” Evidence for somatotopy in the primary interoceptive sensory cortex is presented, and the organization of the mid-insula and the anterior insula is discussed. Issues that need to be addressed are highlighted. A possible basis for subjectivity in a cinemascopic model of awareness is presented.

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Nat Rev Neurosci. 2009 Jan;10(1):59-70.

How do you feel–now? The anterior insula and human awareness.

Source

Atkinson Research Laboratory, Barrow Neurological Institute, Phoenix, Arizona 85013, USA. bcraig@chw.edu

Abstract

The anterior insular cortex (AIC) is implicated in a wide range of conditions and behaviours, from bowel distension and orgasm, to cigarette craving and maternal love, to decision making and sudden insight. Its function in the re-representation of interoception offers one possible basis for its involvement in all subjective feelings. New findings suggest a fundamental role for the AIC (and the von Economo neurons it contains) in awareness, and thus it needs to be considered as a potential neural correlate of consciousness.