Neurobiology of the chronicisation of pain in children: the memory of pain and its painful memory

[Neurobiology of the chronicisation of pain in children: the memory of pain and its painful memory.]

• Cahana A,   Jones D.    Ann Fr Anesth Reanim. 2007 May 22; [Epub ahead of print]

Programme antalgie postoperatoire et interventionnelle, departement d’anesthesiologie, hopitaux universitaires de Geneve, rue Micheli-du-Crest 24, 1211 Geneve 14, Suisse.

Reviewing the development of nociceptive circuits provides the rationale behind the need to modify and reduce premature painful experiences, especially during the “plastic” neonatal phase. Indeed, if physiological mechanisms of the functional nociceptive system follow a harmonious and predetermined development, it is the individual personal experience, intrinsically random, which will shape the final reactivity of this system and the later painful experience. If pain would not have been the organism’s alarm system, we could have simply compared it by analogy to other sensorial systems, which its development depends exclusively on the presence of environmental stimuli. The eyes wait for light, the ears for sound, the skin to be touched, the tongue to taste and the olfactory bulbs to smell. However with pain it is not the quantitative exposure that determines its development, but rather the context-laden aspects of its affliction which in turn create the complex experience and “memory” of pain. Prolonged, but also “unnecessary” exposure to pain transforms it into a futile sensation, which impacts the individual immediately but also resonates into its future. This article reviews recent neurobiological mechanisms (such as neural circuitry, neurotrophins, peripheral and central sensitization, inhibitory pathways) now known to develop during the chronicisation and apprenticing of pain in the growing individual. Its cognizance is vital for a better comprehension of adult pain.

PMID: 17524600 [PubMed - as supplied by publisher]

Complex regional pain syndrome (CRPS)

Hs05 crps – current ideas on management.  ANZ J Surg. 2007 May;77 Suppl 1:A34  

• Shipton EA.

Complex regional pain syndrome (CRPS) is characterised by extreme pain and dysfunction of the sympathetic nervous system in one region of the body, usually an extremity.(1) It involves the somatosensory, sympathetic and the somato-motor systems. It consists of local neurogenic inflammation out of proportion to injury; severe pain in the skin, subcutaneous tissues and joints; and central hyperexcitability that is often compounded with a sympathetic component. It is multifaceted manifesting both central and peripheral neurologic pathophysiology, including a prominent psychosocial component. Mechanisms include trauma related cytokine release, exaggerated neurogenic inflammation, sympathetic afferent coupling, adrenoreceptor pathology, glial cell activation and cortical reorganisation.(2) Diagnostic criteria and tests used will be discussed. Biomedical interventions include the use of primary and secondary analgesics, neural blockade, sympatholysis, ketamine, bisphosphonates, and spinal cord/peripheral nerve stimulation. Psychological and behavioural factors can exacerbate the pain and dysfunction associated with CRPS.(3) Mirror visual feedback was introduced recently for rehabilitation but needs to be evaluated in randomized controlled trials.(4).

PMID: 17490115 [PubMed - in process]

Mirror box therapy added to cognitive behavioural therapy in three CRPS type I

Mirror box therapy added to cognitive behavioural therapy in three chronic complex regional pain syndrome type I patients: a pilot study.

Int J Rehabil Res. 2007 Jun;30(2):181-8

• Vladimir Tichelaar YI,  Geertzen JH, Keizer D, Paul van Wilgen C.

aUniversity Medical Centre Groningen, University of Groningen bCentre for Rehabilitation cNorthern Centre for Health Care Research dDepartment of Anaesthesiology, Pain Centre, University Medical Centre Groningen, University of Groningen, The Netherlands.

Complex regional pain syndrome type I is a disorder of the extremities with disability and pain as the most prominent features. This paper describes the results of cognitive behavioural therapy combined with mirror box therapy in three patients with chronic complex regional pain syndrome type I. Before, during and at follow-up the following measurements were assessed: pain (visual analogue scale, 0-100), range of motion, muscle strength, and the areas of allodynia and of hyperalgesia. Furthermore, patients were asked for their feelings and thoughts about mirror box therapy and about the affected limb. Pain at rest, pain after measuring allodynia/hyperalgesia and pain after measuring strength decreased. Range of motion improved in two patients. Strength improved in one patient. The area of hyperalgesia increased for all three patients, whereas the area of allodynia remained stable in two patients and decreased in one patient. Two patients felt that their affected limb still belonged to them, one did not. Cognitive behavioural therapy combined with mirror box therapy for patients with chronic complex regional pain syndrome type I may facilitate rehabilitation. Measuring whether the affected limb still belongs in the patient’s body scheme could be of prognostic value in the treatment of chronic complex regional pain syndrome type I patients.

PMID: 17473633 [PubMed - in process]

Body perception disturbance in Pain

 Pain. 2007 May 15; [Epub ahead of print

Body perception disturbance: A contribution to pain in complex regional pain syndrome (CRPS).

• Lewis JS, Kersten P, McCabe CS, McPherson KM, Blake DR.

The Royal National Hospital for Rheumatic Diseases NHS Foundation Trust, Bath, UK; The School of Health Professions and Rehabilitation Sciences, University of Southampton, Southampton, UK.

In spite of pain in the CRPS limb, clinical observations show patients pay little attention to, and fail to care for, their affected limb as if it were not part of their body. Literature describes this phenomenon in terms of neurological neglect-like symptoms. This qualitative study sought to explore the nature of the phenomenon with a view to providing insights into central mechanisms and the relationship with pain. Twenty-seven participants who met the IASP CRPS classification were interviewed using qualitative methods to explore feelings and perceptions about their affected body parts. These semi-structured interviews were analysed utilising principles of grounded theory. Participants revealed bizarre perceptions about a part of their body and expressed a desperate desire to amputate this part despite the prospect of further pain and functional loss. A mismatch was experienced between the sensation of the limb and how it looked. Anatomical parts of the CRPS limb were erased in mental representations of the affected area. Pain generated a raised consciousness of the limb yet there was a lack of awareness as to its position. These feelings were about the CRPS limb only as the remaining unaffected body was felt to be normal. Findings suggest that there is a complex interaction between pain, disturbances in body perception and central remapping. Clinically, findings support the use of treatments that target cortical areas, which may reduce body perception disturbance and pain. We propose that body perception disturbance is a more appropriate term than 'neglect-like' symptoms to describe this phenomenon.

PMID: 17509761 [PubMed - as supplied by publisher]

Cerebral mechanisms involved in the interaction between pain and emotion

 Rev Neurol (Paris). 2007 Feb;163(2):169-79                Article in French]

Duquette M, Roy M, Lepore F, Peretz I, Rainville P.

Departement de Psychologie, Universite de Montreal, Montreal, Quebec, Canada.

INTRODUCTION: Pain is an unpleasant and intrusive sensation, warning of actual or potential tissue damage. Over the last fifteen years, functional cerebral imaging research has demonstrated the involvement of many cerebral structures in the experience of pain. BACKGROUND: Intimately linked to the notion of suffering, the affective dimension of pain relies on neurophysiological systems partly distinct anatomically from those involved more specifically in its sensory dimension. Some pathways convey nociceptive information to the somatosensory cortex and the insula, contributing to the sensory aspects of pain (e.g.: sensory intensity), and secondarily, to its affective dimension. Other pathways project directly to the anterior cingulate cortex, the insula, the amygdala and to the prefrontal cortices, which are structures involved in the affective dimension of pain (unpleasantness of pain and regulation of autonomic and behavioral responses). Interestingly, these latter regions are an integral part of the cerebral emotional networks. PERSPECTIVES AND CONCLUSION: This close anatomical relationship between pain and emotions circuits could explain the powerful emotional impact of pain as well as the reciprocal modulatory effect of emotions on pain observed in clinical and experimental studies. More specifically, this modulatory effect might reflect interactions between emotional and nociceptive systems in the prefrontal and cingulate cortices, ventral striatum, amygdala and hippocampal regions. Taken together, these observations further attest to the emotional nature of pain experience.

PMID: 17351536 [PubMed - indexed for MEDLINE]

Can Behavioural therapy influence neuromodulation?

 Neurol Sci. 2007 May;28 Suppl 2:S124-9

• Andrasik F,   Rime C.

Department of Psychology, University of West Florida, 11000 University Parkway, Pensacola, FL, 32514, USA, fandrasik@uwf.edu.

This paper reviews non-invasive behavioural approaches – broadly construed as cognitive, affective, behavioural and psychophysiological interventions – and examines whether they can impact central, peripheral or autonomic nervous system components responsive to pain in general and headache in particular. It focuses on two developing bodies of literature – neurophysiology of migraine and fMRI studies of pain networks. The available literature suggests behavioural interventions can affect neuromodulation, although further research is clearly warranted.

PMID: 17508158 [PubMed - in process]

Retrieving autobiographical memories of painful events activates the anterior cingulate cortex and inferior frontal gyrus.

 J Pain. 2007 Apr;8(4):307-14. Epub 2006 Dec 22

• Kelly S, Lloyd D,  Nurmikko T,  Roberts N.

Magnetic Resonance and Image Analysis Research Centre (MARIARC), University of Liverpool, Liverpool, United Kingdom. S.Kelly@Liverpool.ac.uk

Patients will often reflect on the meaning of a painful episode, as, for example, when completing questionnaire measures of subjective pain experience or in clinical interviews. Neuroimaging studies of the human cortical and subcortical physical pain response have identified a neural network consistently referred to as the “pain matrix.” We used functional magnetic resonance imaging to investigate whether the pain matrix could be activated through the retrieval of memories relating to previously painful events, in the absence of any direct peripheral noxious input. Fourteen pain-free participants were explicitly instructed to recall autobiographical memories of painful episodes in response to pain-related words and non-painful episodes in response to equally salient but non-pain words. Memories triggered by pain-related words produced significantly greater activation of left caudal anterior cingulate cortex (BA32′), and left inferior frontal gyrus (BA44, extending to BA47/45) more than memories triggered by equally salient but non-pain words. We suggest that these activations demonstrate a semantic retrieval process for pain-related memories, which may provide a means of cognitively reappraising the memory of the painful episode, thus allowing the person to elaborate on the circumstances surrounding the event, without physically re-experiencing it. PERSPECTIVE: The present study reveals a putative neural mechanism for the retrieval of autobiographical memories of previously painful events, which may provide a means of cognitively reappraising a painful episode, without physically re-experiencing it. This finding has implications for understanding disease mechanisms of chronic pain and their impact on subsequent treatment.

PMID: 17188577 [PubMed - in process]

Empathy for Pain and Touch in the Human Somatosensory Cortex

 Cereb Cortex. 2007 Jan 6; [Epub ahead of print

Bufalari I,    Aprile T,  Avenanti A,   Di Russo F,   Aglioti SM.

Dipartimento di Psicologia, Universita degli studi di Roma "La Sapienza", I-00185 Rome, Italy.

Although feeling pain and touch has long been considered inherently private, recent neuroimaging and neurophysiological studies hint at the social implications of this experience. Here we used somatosensory-evoked potentials (SEPs) to investigate whether mere observation of painful and tactile stimuli delivered to a model would modulate neural activity in the somatic system of an onlooker. Viewing video clips showing pain and tactile stimuli delivered to others, respectively, increased and decreased the amplitude of the P45 SEP component that reflects the activity of the primary somatosensory cortex (S1). These modulations correlated with the intensity but not with the unpleasantness of the pain and touch ascribed to the model or the aversion induced in the onlooker by the video clips. Thus, modulation of S1 activity contingent upon observation of others' pain and touch may reflect the mapping of sensory qualities of observed painful and tactile stimuli. Results indicate that the S1 is not only involved in the actual perception of pain and touch but also plays an important role in extracting somatic features from social interactions.

PMID: 17205974 [PubMed - as supplied by publisher]

nocebo effect

When words are painful: Unraveling the mechanisms of the nocebo effect

1: Neuroscience. 2007 Mar 20; [Epub ahead of print

Department of Neuroscience, University of Turin Medical School, Corso Raffaello 30, 10125 Turin, Italy.

The nocebo effect is a phenomenon that is opposite to the placebo effect, whereby expectation of a negative outcome may lead to the worsening of a symptom. Thus far, its study has been limited by ethical constraints, particularly in patients, as a nocebo procedure is per se stressful and anxiogenic. It basically consists in delivering verbal suggestions of negative outcomes so that the subject expects clinical worsening. Although some natural nocebo situations do exist, such as the impact of negative diagnoses upon the patient and the patient's distrust in a therapy, the neurobiological mechanisms have been understood in the experimental setting under strictly controlled conditions. As for the placebo counterpart, the study of pain has been fruitful in recent years to understand both the neuroanatomical and the neurochemical bases of the nocebo effect. Recent experimental evidence indicates that negative verbal suggestions induce anticipatory anxiety about the impending pain increase, and this verbally-induced anxiety triggers the activation of cholecystokinin (CCK) which, in turn, facilitates pain transmission. CCK-antagonists have been found to block this anxiety-induced hyperalgesia, thus opening up the possibility of new therapeutic strategies whenever pain has an important anxiety component. Other conditions, such as Parkinson's disease, although less studied, have been found to be affected by nocebo suggestions as well. All these findings underscore the important role of cognition in the therapeutic outcome, and suggest that nocebo and nocebo-related effects might represent a point of vulnerability both in the course of a disease and in the response to a therapy.

PMID: 17379417 [PubMed - as supplied by publisher]

Transition from acute to chronic pain

Transition from acute to chronic pain and disability: A model including cognitive, affective, and trauma factors

Young Casey C, Greenberg MA, Nicassio PM, Harpin REHubbarD.

Department of Psychiatry, University of California, San Diego, School of Medicine, La Jolla, CA, USA.

This study evaluated a theoretically and empirically based model of the progression of acute neck and back pain to chronic pain and disability, developed from the literature in chronic pain, cognition, and stress and trauma. Clinical information and standardized psychosocial measures of cumulative traumatic events exposure (TLEQ), depressed mood (CES-D), pain (DDS), physical disability (PDI), and pain beliefs (PBPI) were collected at baseline from 84 acute back pain patients followed at an Acute Back Clinic over 3months. Path analysis was used for the longitudinal prediction of perceived pain and disability. The predictive model accounted for 26% of the variance in persistent pain intensity and 58% of the variance in perceived physical disability at 3months. Greater exposure to past traumatic life events and depressed mood were most predictive of chronic pain; depressed mood and negative pain beliefs were most predictive of chronic disability. More cumulative traumatic life events, higher levels of depression in the early stages of a new pain episode, and early beliefs that pain may be permanent significantly contribute to increased severity of subsequent pain and disability. Replication in a larger sample is desirable to confirm these paths. Early detection of elevated depressive symptoms and high trauma exposure may identify individuals at greater risk for developing chronic pain syndromes who may benefit from early multidisciplinary intervention.

PMID: 17504729 [PubMed - as supplied by publisher]

Disruption of attention and memory in chronic pain.

Disruption of attention and working memory traces in individuals with chronic pain.

• Dick BD,
• Rashiq S.

Department of Anesthesiology and Pain Medicine, University of Alberta, Edmonton, AB, Canada. bruce.dick@ualberta.ca

BACKGROUND: Research has found that chronic pain disrupts attention and that this disruption can lead to significant functional impairment and decreased quality of life. We conducted the present study to examine how attention and memory are disrupted by chronic pain. METHODS: Computerized tests of working memory were given to participants with chronic pain along with a neuropsychological test of attention before and after procedures resulting in analgesia. RESULTS: Two-thirds of participants with chronic pain had scores in the clinically impaired range on attentional tasks. These results were independent of age, education level, sleep disruption, and pain relief. Medication use was also recorded and is reported to account for potential effects of medication on task performance. Those participants with the highest level of impairment had significantly greater difficulties in maintaining a memory trace during a challenging test of working memory. CONCLUSIONS: These findings point to a specific cognitive mechanism, the maintenance of the memory trace, that is affected by chronic pain during task performance. Cognitive function was not improved by short-term local analgesia.

PMID: 17456678 [PubMed - in process]

Brain’s White Matter Is ‘Talkative’

.S. scientists have discovered nerves in the mammalian brain’s white matter process information much in the same manner as gray matter cells.The surprising discovery in mouse cells by Johns Hopkins University researchers show brain cells “talk” with each other in more ways than previously thought.

The discovery focuses on oligodendrocyte precursor cells, or OPCs, whose main role when they mature into oligodendrocytes is to insulate nerves with a whitish coat of protective myelin. The immature cells simply hang around and divide very slowly, waiting to be spurred into action

[Brain plasticity after stroke - implications for post-stroke rehabilitation.]

Tidsskr Nor Laegeforen. 2007 May 3;127(9):1228-31.

[Article in Norwegian]

• Dietrichs E.

Nevrologisk avdeling Nevroklinikken Rikshospitalet-Radiumhospitalet 0027 Oslo og Fakultetsdivisjon Rikshospitalet Universitetet i Oslo. espen.dietrichs@medisin.uio.no.

BACKGROUND:In the last ten years, increased understanding of the brain’s plasticity has opened up new possibilities for post-stroke rehabilitation. MATERIAL AND METHODS:The article is based on a literature search in Medline, my own research and clinical experience. RESULTS:Post-stroke brain plasticity includes synaptogenesis, change of function in pre-existing synapses, cortical reorganization and probably neurogenesis. All these changes are stimulated by activity. The brain may be more susceptible to plasticity changes shortly after damage has occurred. Clinical studies have shown that intensive rehabilitation training is better than moderate training to recover motoric functions. Cortex contralateral to the lesion is activated in post-stroke motor training, but the pattern of cortical activation is normalized as function is regained. The prognosis is better if some of the relevant motor circuits are left undamaged. Sensory stimulation may also enhance motor recovery. INTERPRETATION:The ideal form of rehabilitation training is still unclear, but we do know that post-stroke rehabilitation should start as soon as possible, with good motivation, sufficient intensity and quantity, and should be maintained over a long time.

PMID: 17479145 [PubMed - in process]

Pain, cortex, and consciousness

Behav Brain Sci. 2007 Feb;30(1):89-90.

• Devor M.

Department of Cell and Animal Biology, Institute of Life Sciences and Center for Research on Pain, Hebrew University of Jerusalem, Jerusalem, 91904, Israel. marshlu@vms.huji.ac.il.

Painful stimuli evoke functional activations in the cortex, but electrical stimulation of these areas does not evoke pain sensation, nor does widespread epileptic discharge. Likewise, cortical lesions do not eliminate pain sensation. Although the cortex may contribute to pain modulation, the planning of escape responses, and learning, the network activity that constitutes the actual experience of pain probably occurs subcortically.

PMID: 17475061 [PubMed - in process]

Plastic Brain

The brain can rapidly reorganise to recover from damage

The brain can transfer specific functions to new areas when part of it is damaged, according to Oxford research.

The findings, published in Neuron, are relevant to understanding processes of recovery after stroke.

When brain damage occurs in stroke patients, activity in undamaged parts of the brain often increases. This is particularly prominent in patients with poor recovery.

However, it was not clear whether this was a cause of slow recovery, with activity in the brain becoming chaotic, or part of an adaptive process that helps recovery – the brain trying hard to transfer function over to the healthy hemisphere.

To find out, Dr Jacinta O’Shea and colleagues in the Department of Experimental Psychology and the Centre for Functional MRI of the Brain simulated brain damage in healthy volunteers by using transcranial magnetic stimulation (TMS), temporarily disrupting normal activity in the premotor cortex (a part of the brain that enables people to select which movement to make).

Participants were then asked to perform a task whose success depended on normal levels of activity in the premotor cortex: they had to make one of two finger movements depending on which of several shapes was presented on a computer screen.

As would be expected, after the simulated brain damage participants were initially slower at selecting the correct response. However, after four minutes, performance was back to normal. ‘This suggested to us that the brain might have reorganised itself to compensate for the interference’, says Dr O’Shea.

By imaging participants’ brains, the researchers confirmed that during recovered performance there was increased activity in undisrupted parts of the brain. As final confirmation, they tried disrupting one of the newly active brain areas – and, as predicted, performance on the task was once again impaired. The function of the ‘damaged’ brain area had been moved to the ‘healthy’ half of the brain.

The transfer was specific to the function of the premotor cortex, and it happened only when it was needed for the job,’ said Dr O’Shea. ‘The speed of the reorganisation was also impressive: the brain temporarily reconfigured itself in a matter of minutes.

‘Our findings show just how flexible the brain is.’

Source: University of Oxford