Clinical psychophysiology of pain

Despite major progress in the analysis of acute pain, the causes of chronic pain remain largely unknown. Research on the role of psychological factors in the development of chronic pain is especially lacking. Based on the psychobiological model of chronic pain that was proposed by our group (Flor, Birbaumer & Turk, 1990) six projects, financed by the Deutsche Forschungsgemeinschaft (DFG) assess psychological mechanisms of the pro-cessing of painful stimulation and factors contributing to chronicity. The central nervous and peripheral physiological correlates of these psychological influences are the focus of our analysis. Learning processes, information processing and emotional influences on pain perception are examined in healthy controls, subjects with heightened pain sensitivity (chronic back pain patients, phantom limb patients), subjects with reduced pain sensitivity (hypertensives) and patients with various degrees of chronicity. The comparison of various age and patient groups permits conclusions about the development and maintenance of chronic pain. These experiments increase our understanding of chronic pain and offer a scientific basis for the interdisciplinary prevention and treatment of chronic pain which addresses causal mechanisms. The six projects examine various clinical groups, each with a different scientific focus. In addition to psychophysical methods, cognitive-psychological, approaches, classical and instrumental conditioning, peripheral physiological measures (EMG, heart rate, skin conductance temperature, blood pressure, startle reflex) and central physiological variables (non-linear EEG dynamics, dipole analyses, evoked potentials and DC-potentials) are used in all projects. In addition to the clinical application of the results there are further developments in our psychobiological theory of chronic pain development. This theory will permit predictions about the differential development of pain (who develops chronic pain?) and differential assignment to treatment (which treatment is best for whom?). The six projects examine three essential psychological functions of the processing of painful stimulation:

Project 1 (Flor/Birbaumer) addresses operant conditoning mechanisms of pain, project 2 (Birbaumer/Flor) respondent conditioning and the formation of pain-related memories, projects 3 (Miltner/Lutzenberger) and 4 (Rau) examine the cortical correlates of pain perception and the interactions of cardiac and cortical physiological processes. Project 5 (Daum/Ackermann) further clarifies the local cortical representation of pain by testing patients with defined CNS lesions. Project 6 (Larbig/Weller) examines psychophysiological mechanisms of pain perception and the role of emotional variables in the development and maintenance of phantom limb pain.

Evidence for extensive reorganization of the somatosensory cortex in adult humans after nervous system injury In 12 unilateral upper extremity amputees, the topographic representation of the face area, which lies adjacent to the cortical amputation zone was found to be altered. Magnetic source imaging revealed that the focus of cortical activation to peripheral stimulation was shifted 1-2 cm from this cortical region toward the area that would normally receive input from the now absent nerves supplying the hand and fingers. A similar tendency was observed for the upper arm (stump) area. The additional responsivity of these cortical areas was accompanied by an enhanced power of evoked electroencephalographic potential and magnetic field wave forms. Observed alterations provide evidence for extensive plastic reorganization in the adult cortex following nervous system injury. They may constitute the neurophysiological basis of some phantom limb phenomena; however, they are not a sufficient cause of "facial remapping". The figure on the front cover shows magnetically evoked fields (MEG, upper traces) and the electrically evoked somatosensory potentials (EEG, below) from a patient with amputation of the right arm. The central part shows the magnetic resonance image (MRI) of the patient's brain with current dipoles and posterior right and left cerebral cortex. (With friendly permission from Elbert et al., 1994.)

Birbaumer, N., Flor, H., Lutzenberger, W. & Elbert, T. (1995). The Corticalization of Pain. In Bromm, B., & Desmedt, J. (Eds): Pain and the brain. New York: Raven.

Elbert, T., Flor, H., Birbaumer, N., Knecht, St., Hampson, S., Larbig, W. & Taub, E. (1994). Extensive Reorganization of the Somatosensory Cortex in Adult Humans after Nervous System Injury. Neuroreport , 5, 2593-2597.

Flor, H., Elbert, T., Knecht, S., Wienbruch, C., Pantev, C., Birbaumer, N., Larbig, W., Taub, E. (1995). Phantom-limb pain as a perceptual correlate of cortical reorganisation following arm amputation. Nature, 375, 482-484.

Larbig, W., Bauersfeld, G., Karmann, J., Fürst, M., Flor, H., Bilow, H., Weller, S., Birbaumer, N. (1993). Memory for pain in phantom limb pain patients: Central and peripheral correlates. Psychophysiology 1, 9.

Dimensional and spectral analysis of the EEG during experimentally induced and recalled pain in chronic pain patients and healthy controls

The purpose of this study was the determination of the relationship between the dimensional complexity and power spectra of the electroencephalogram (EEG) and the actual experience of pain as well as memory for pain in 9 chronic pain patients and 9 matched healthy controls. During a resting phase and various heat pain induction phases as well as pain recall and imagery conditions the EEG was recorded from fifteen scalp sites. Nonlinear analysis, based on the theory of deterministic chaos, revealed no differences in the complexity of the EEG for the painful compared to the non-painful stimulation but confirmed previous findings of increased complexity for imagery compared to the perception of pain. The personal pain scene induced more complex and widespread EEG complexity in the patients compared to the healthy controls. The self-controlled pain exposure led to a marked hemispheric difference in complexity. More pain-tolerant subjects showed less dimensional complexity when exposed to pain than less pain tolerant sujects. The power spectra measures revealed few consistent effects except for the previously reported but difficult to interpret increase in beta activity during painful stimulation. These data suggest that chronic pain patients have more extensive memories for personal pain represented in wider cell assembly activation when the memory is probed.

Birbaumer, N., Lutzenberger, W., Flor, H. & Elbert, T. (1993). Non-linear Complexitiy of Neural Activity. Neuroscience Abstracts 19, 1606.

Flor, H. & Birbaumer, N. (1994). Acquisition of Chronic Pain: Psychophysiological Mechanisms. American Pain Society Journal, 3, 119-127.

Lutzenberger, W., Flor, H. & Birbaumer, N. (1993). Dimensional and Spectral Analysis of the EEG during Induced and Recalled Pain in Chronic Pain Patients and Healthy Controls. Psychophysiology 30, (Supplement 1), 44.

Chronic pain enhances the magnitude of the magnetic field evoked at the site of pain

It has been assumed that chronic stimulation leads to changes in the cortical representation of pain, specifically to changes in receptive fields in the somatosensory cortex. Consequently, cortically evoked magnetic fields should result from more extended sources when evoked from the affected body part of a patient. Nine patients who suffered from continuous chronic low back pain of either muscular or degenerative origin (IASP diagnosis of category XXVII) and nine matched controls participated in the study. Sub-threshold-, supra-threshold (painful), and control stimuli (500 ╡A) were applied at either the site of most intense pain or at the left index finger. Using a BTi Neuromagnetometer, magnetic fields were recorded from 37 locations over the somatosensory cortex. The evoked fields were extracted across channels. With increasing duration of the illness sensitivity to somatosensory stimulation at the affected site is increased (r> .5, p<.05). The magnitude of the earlier aspect of the magnetically evoked fields (MEF 80-125 ms) were significantly elevated in the subgroup of very chronic (> 7 years pain duration) patients, whereas the subchronic group's evoked fields were not significantly different from those of healthy controls. These associations were produced only when stimuli were applied to the back but did not become evident for the control site or for auditory evoked fields (Figure 3). Later components of the MEF (> 150 ms) were enhanced in the chronic group regardless of the site of stimulation. The MEF prior to 80 ms did not reflect group differences. Patients who experience chronic noxious stimulation over extended periods of time produce more extensive activation of neural assemblies when phasic somatosensory stimuli are applied to the location of their pain. This result is in accordance with observations from animal experiments demonstrating the plasticity of receptive fields subequent to longterm alterations of afferent input.

Flor, H., Birbaumer, N., Braun, Ch., Elbert, T., Ross, M. & Hoke, M. (1993). Chronic Pain Enhances the Magnitude of the Magnetic Field Evoked at the Site of Pain. Neuroscience Abstracts 19, 233.

Flor, H., Birbaumer, N., Braun, Ch., Elbert, T., Ross, M. & Hoke, M. (1994). Chronic Pain Enhances the Magnitude of the Magnetic Field Evoked by Painful Stimulation. In Deecke, L., Baumgartner, C., Stroink, G. & Williamson, S.J. (Eds): Recent Advances in Biomagnetism. Amsterdam: Elsevier, 72-73.

Opioid mediation of conditioned stress-induced analgesia in humans

The existence of both opioid and nonopioid conditioned stress analgesia has been shown in animals. In humans there is some preliminary evidence for conditioned stress analgesia. The purpose of this study was to confirm the existence of conditioned stress analgesia in humans and to determine whether it is opioid-mediated. A differential classical conditioning design with auditory conditioned stimuli and mental arithmetic as the unconditioned stimuli was used. During test sessions placebo or naloxone were applied in a double-blind fashion. Both pain threshold and pain tolerance (electrical stimulation-induced) were increased in response to the conditioned stimulus as compared to the control stimulus. The application of naloxone removed the conditioned analgesia with respect to pain tolerance; pain threshold was only marginally influenced. These results show that conditioned analgesia may be produced by stress in humans and that the expression of this effect may be mediated by the endogenous opioid system.

Flor, H. & Birbaumer, N. (1994). Basic Issues in the Psychobiology of Pain. In G.F.Gebhart et al. (Eds): Proceedings of the VIth World Congress on Pain. IASP, pp. 113-125. Amsterdam: Elsevier.

Mucha, R. F., Flor, H., Schulz, R., Birbaumer, N., Larbig, W. (1994). Naloxone-reversible analgesia produced by a stimulus paired with a cognitive stressor: a differential conditioning study in humans. Behavioural Pharmacology, 5, (Suppl.1), 94.

A psychophysiological analysis of operant reinforcement, spouse interaction, and pain perception

The purpose of this study was the determination of the relationship of marital interaction, spouse reinforcement, the perception of acute pain stimuli, and psychophysiological reactivity. Seventeen chronic back pain patients and fifteen matched healthy controls and their significant others participated in the study. A psychophysiological assessment was performed during two cold pressor tests (one with the spouse present, the other with the spouse absent) and a neutral and a conflictual verbal interaction. The interactions were videotaped and analyzed by a marital interaction coding system. Heart rate, blood pressure, skin conductance level and electromyographic data from the m. erector spinae and the m. splenius capitis were recorded. Increased solicitousness of the spouses was related to lower pain threshold and pain tolerance in the spouse present condition for the patients only. Psychophysiological reactivity was not significantly different for patients and controls during the two cold pressor tests but was elevated at the lower back for the patients in the conflictual interaction. The healthy controls showed generally elevated neck muscle activity during interaction, the interaction of the patients was generally more positive especially if solicitousness was high. The subjective ratings were consistent with the behavioral and psychophysiological findings. These data suggest that increased positive reinforcement of pain behaviors by significant others is associated with heightened pain perception in chronic pain patients. Psychophysiological reactivity seems to be related to patient status only but not to solicitousness.

Breitenstein, C., Flor, H. & Birbaumer, N. (1994). Kommunikations- und Problemlöse-verhalten von chronischen Schmerzpatienten und ihren Partnern, Zeitschrift für Klinische Psychologie, 23, 2, 105 -116.

Flor, H., Breitenstein, C. & Schlottke, P.F. (1993). Psychobiologische Grundlagen. In F.Petermann et al. (Eds): Schmerz im Kindes- und Jugendalter. Göttingen: Hogrefe.

Flor, H., Breitenstein, C., Birbaumer, N. & Fürst, M. (1995). A Psychophysiological Analysis of Operant Reinforcement, Spouse Interaction, and Pain Perception. Behavior Therapy 26, 255 - 272.

Knost, B., Flor, H., Fürst, M., Grimminger, U., Breitenstein, C. & Birbaumer, N. (1993). Psychophysiological Reactivity of Chronic Back Pain Patients and Healthy Controls during Marital Conflict. Psychophysiology 30, 40.

Muscular and cortical classically conditioned responses in chronic pain patients, subjects at high risk for chronic pain and healthy controls

The theory was tested that the development of chronic pain with or without a known pathophysiology is conceptualized as classical conditioning of pathophysiological peripheral (i.e. muscular) nociceptive responses, some of which are maintained through instrumental learning (i.e. avoidence of painful positions, attention). The central nervous correlates of these conditioning processes then form a pain-memory and pain memories are seen as dynamic cortico-subcortical cell assemblies which can be "ignited" by pain-associated physical or psychological conditioned stimuli. A series of classical-conditioning experiments with low back pain patients, healthy controls and subjects with a high risk for developing chronic pain were conducted. The data confirm our theory: a) electric cortical responses to painful stimuli are larger and anatomically more widespread in patients, b) classical conditioning of muscular tension to painful stimuli occurs faster and is more resistent to extinction in patients, c) the cortical cell assemblies responsible for the conditioned stimuli at very early stages (100-150 ms) are altered and late stages show more extensive processing, indicated by late ("emotional") positivities.

Flor, H., Birbaumer, N. (1994). Acquisition of chronic pain: Psychophysiological mechanisms. American Pain Society Journal 3, 119-127.

Flor, H., Birbaumer, N., Fürst, M., Lutzenberger, W., Elbert, T. & Braun C. (1993). Evidence of enhanced peripheral and central responses to paonful stimulation in chronic pain. Psychophysiology, 30, 9.

Cortical Correlates of Pavlovian Conditioning

Classical conditioning is a basic learning paradigm, which may be important for the acquisition of pain and fear. So far the role of cortical processes for the acquisition, storage and extinction of conditioned responses in humans is unknown. Based on Hebbian cell assembly theory we have postulated that local cell assemblies in the primary cortical areas as well as global cortical-subcortical and cortical-cortical cell assemblies are modified during associative learning. This study determinated the relationship between the contingent negative variation (CNV) and the acquisition and extinction of a classically conditioned muscular response. It was assumed that the early component of the CNV (initial CNV, iCNV) might represent the amount of anticipatory arousal with respect to the US that is elicited by the CS and would thus be especially sensitive to changes in meaning of the CS over time. The late component of the CNV (terminal CNV, tCNV) should indicate preparation for the CR. 48 subjects were randomly assigned to three groups with slides of angry faces as CS+ and happy faces as CS-, the reverse condition, or neutral faces as CS+ and CS-, respectively. The UCS consisted of a bipolar electrical impulse of 20-millisecond duration delivered via a gold electrode that was implanted intracutaneously at the left index finger. In addition to forearm (m. flexor digitorum) and corrugator EMGs, heart rate, skin conductance, and slow cortical potentials (SCPs, at Fz, Cz, Pz, C3 and C4) were recorded using 5-second ISIs. After 10 habituation trials, 60 acquisition trials (30 CS+, 30 CS-) and 30 extinction trials (15 CS+, 15 CS-) followed in pseudo-random order with a limit of 3 consecutive presentations of CS+ and CS- The analyses showed that all three groups equally acquired the peripheral CRs with no significant differences in resistance to extinction. During acquisition both the iCNV and the tCNV were significantly higher to the CS+ as compared to the CS-, with maxima at Cz and C4 for the tCNV, and at Fz for the iCNV. The tCNv was more pronounced to the neutral slide CS+ during acquisition. The iCNV was significantly higher during extinction when a happy face CS+ had served as CS+. Neither N1 nor P3 were sensitive to the CS+/- differentiation. The analysis of the course of the conditioning (blocks of 5) revealed clear increases for both iCNV and tCNV over the course of the acquisition and great sensitivity for changes in expectancy which could be seen at the beginning of the aquisition and extinction phases, respectively. Towards the end of the acquisition phase the negativity became more focused to C3 and C4. There was a low but significant correlation between the height of the CNV and the CR. We conclude from these data that the CNV may be a useful measure of the associative process during Pavlovian conditioning. It reflects the CS-US association as well as a preparatory process which may in part determine CR strength.

Flor, H. & Birbaumer, N.(1994). Bais Issues in the Psychobiology of Pain. In: G.F. Gebhart, D.L. Hammond & T.S. Jensen (Eds.), Proceedings of the VIIth World Congress on Pain, pp. 113 - 125. Amsterdam: Elsevier.

Flor, H., Vaitl, D. & Birbaumer, N. (1993). Lernen in physiologischen Systemen: Grundlagen und Anwendung. In L.Montada (Ed): Bericht über den 38. Kongre&& der Deutschen Gesellschaft für Psychologie in Trier 1992, Bd.2, Göttingen: Hogrefe.

Flor, H., Roberts, L., Birbaumer, N., Fürst, M., Lutzenberger, W. & Herrmann, C. (1993). Cortical correlates of Pavlovian conditioning (submitted).

Assessment and treatment of chronic pain

The Psychophysiological Pain Clinic of the Institute of Medical Psychology and Behavioral Neurobiology was founded in 1986 to develop and evaluate psychophysiological procedures designed to improve the assessment and management of ttherapy-resistent states of chronic pain. The comprehensive assessment scheme covers standardized physiological-organic, verbal-subjective, behavioral and psychophysiological aspects of the pain experience and is used for the differential indication of treatments. Several treatment outcome studies evaluate the efficacy of psychological treatments for chronic pain such as EMG-biofeedback, operant behavior therapy, cognitive-behavioral pain management in comparison to or in combination with medical-somatic treatments for chronic pain. These studies are conducted in close cooperation with the Department of Neurology, the School of Dental Medicine, the Berufsgenossenschaftliche Accident Clinic, the Department of Neuroradiology and the Clinic of Anaesthesiology. Subgroups of Chronic Pain Patients Identified by Cluster Analysis The purpose of this study was the identification of subgroups of chronic pain patients with common psychological and physiological-organic characteristics. Two samples of 200 and 150 patients each were tested. They participated in a comprehensive pain assessment that included medical-somatic (e.g. MEDICS), verbal-subjective (e.g. WHYMPI), behavioral (e.g. TBS) and psychophysiological (e.g. EMG-reactivity to cold pressor pain) measures of pain. A k-mean cluster analysis yielded four groups of chronic pain patients namely, a distressed/stressed group, a group with high levels of instrumental pain behaviors, a physiologically highly reactive group and a group of patients who were coping well with their pain. This cluster composition was replicated in the second sample. We believe that these different patient subgroups should profit from individualized medical and psychological treatments for chronic pain.

Flor, H., Birbaumer, N. (1993). Verhaltensmedizinische Grundlagen. In Zenz, M. , Jurna, I. (Hrsg.), Lehrbuch der Schmerztherapie. Stuttgart: Wissenschaftliche Verlagsgesellschaft, 95-106

Flor, H. & Birbaumer, N.(1994). Bais Issues in the Psychobiology of Pain. In: G.F. Gebhart, D.L. Hammond & T.S. Jensen (Eds.), Proceedings of the VIIth World Congress on Pain, pp. 113 - 125. Amsterdam: Elsevier.

Assessment of Pain-related Cognitions in Chronic Pain Patients

The construction of the pain-related self-statements scale (PRSS) and the Pain-Related Control Scale (PRCS) is described. The PRSS assesses situation-specific aspects of patient's cognitive coping with pain while the PRCS measures general attitudes toward the pain. The reliability and validity of the scales were determined in a sample of 120 chronic pain patients suffering from various rheumatic disorders, 213 patients who suffered from chronic back pain, 44 patients with temporomandibular pain and dysfunction and 38 healthy controls. The analysis of the PRSS yielded two scales termed "Catastrophizing" and "Coping", the PRCS consists of the subscales "Helplessness" and "Resourcefulness". All four subscales were demonstrated to be valid and sensitive to change, and they are clearly related to pain intensity and interference in social and psychological functioning of pain experiences.

Flor, H., Behle, D.B. & Birbaumer, N. (1993). Assessment of Pain-related Cognitions in Chronic Pain Patients. Behaviour Research and Therapy, 31, 63 - 67.

Flor, H. & Junger, U. (1994). Kognitive Verhaltenstherapie bei Schmerzen. In Hautzinger, M. (Ed): Kognitive Verhaltenstherapie bei psychiatrischen Erkrankungen. München: Quintessenz.

Comparison of the efficacy of EMG biofeedback, cognitive behavior therapy and conservative medical interventions in the treatment of chronic musculoskeletal pain

The purpose of this study was to compare three types of treatments for chronic musculoskeletal pain. Fifty-seven patients who suffered from chronic back pain and 21 patients who suffered from temporomandibular pain and dysfunction were randomly assigned to either EMG-biofeedback, cognitive behavior therapy, or conservative medical treatment. At post-treatment, improvements were noted in all three treatment groups with the biofeedback group displaying the most substantial change. At the 6- and 24-month follow-up only the biofeedback group maintained significant reductions in pain severity, interference, affective distress, pain-related use of the health care system, stress-related reactivity of the affected muscles, and an increase in active coping self-statements. Treatment outcome was predicted by chronicity, as well as treatment-specific variables. Analysis of attrition showed a significant effect for therapist and extent of somatic pathology. This study suggests that pain patients with musculoskeletal pain problems and few physical disabilities may profit most from short-term EMG-biofeedback treatment.

Flor, H. & Birbaumer, N. (1993). Comparison of EMG-Biofeedback, Cognitive behavior Therapy, and Conservative Medical Treatment for Chronic Musculoskeletal Pain. Journal of Consulting and Clinical Psychology, 61, 653 - 658.

Flor, H. & Birbaumer, N. (1993). Neue Verfahren der Schmerzbehandlung: Die Wirksamkeit von EMG-Biofeedback, kognitiver Verhaltenstherapie und konservativer medizinischer Behandlung bei der Therapie von chronischen Schmerzzuständen der Skelettmuskulatur. Der Schmerz, 7, 1.

Flor, H., Birbaumer, N. & Buettner, U.W. (1993). A Way out of the Vicious Circle. German Research, 1, 12-13, 32.

Random versus assessment - based assignment of patients with chronic back pain to operant, cognitive-behavioral, and medical treatment

This study was designed to evaluate (a) the efficacy of operant, cognitive-behavioral, or traditional medical interventions for chronic back pain, and (b) to investigate whether assessment-based assignment of the patients yielded superior results than random assignment. 150 chronic back pain patients underwent a comprehensive medical-somatic, psychophysiological, behavioral, and verbal-subjective pain assessment. Non-random assignments to the treatments were based (a) on clinical judgement following criteria found in the literature and (b) on empirical clustering of the patients into three subgroups. All three treatments were provided on an outpatient basis over a period of 3 months. Follow-up assessments were performed 1 week, 6 months and 12 months post-treatment. Assessment-based assignment of the patients significantly reduced drop-out rates (from > 30% to <10%), but did not lead to superior treatment results overall. Given the different drop-out rates, it may be inferred that assessment-based assignment has a potentially more powerful effect. The three treatments yielded differential effects with the operant treatment showing the most marked long-term improvements. There was a high agreement between the empirical and clinical grouping of the patients. Assessment-guided assignment of patients to psychological or medical interventions increases the efficiency of these treatments and should be prefered to random assignments. A prerequisite for appropriate assignments is the use of comprehensive multilevel assessment procedures.

Flor, H. & Birbaumer, N. (1995). Psychobiologie und interdisziplinäre Therapie chronischer Wirbelsäulensyndrome. Forschungsberichte des Projektträgers. München: GSF Forschungszentrum.


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