Internet-based program for coping with cancer: a randomized controlled trial with hematologic cancer patients.

OBJECTIVE: Psychosocial patient care in oncology is no longer limited to the inpatient setting. Outpatient services are in demand. Internet-based interventions could aid in optimizing service delivery across disciplines. The effectiveness of an Internet-based program for hematologic cancer patients was tested in a randomized controlled trial under field experimental conditions. METHODS: A 4-week cognitive-behavioral program for coping with cancer was offered to hematologic cancer patients online. One hundred eighty-six registrants were randomly assigned to an intervention group (n = 105) or a waiting list (n = 81). The outcome measures, 'mental adjustment' (MAC) and 'psychological distress' (BSI), were assessed at registration and after 4 weeks. Patient satisfaction was assessed (ZUF-8), and complete-cases and intention-to-treat analyses were performed. RESULTS: At registration, the majority of participants displayed clinically significant distress (BSI) and lacked alternative access concerning psychosocial care. One hundred eleven patients filled out the post questionnaire at 4 weeks. In contrast to the waiting list, the intervention group displayed a significant increase in fighting spirit (d = 0.42; CI 95%, 0.04 to 0.80). The effect was confirmed by intention-to-treat analysis (d = 0.33; CI 95%, 0.04 to 0.62). Otherwise, no effects were observed. Patient satisfaction with the program was high. CONCLUSION: The results demonstrate the potential efficacy of Internet-based programs while highlighting their limitations. Future research is needed to clarify and optimize efficacy, taking different program components and patient characteristics into particular consideration.

NMDA-receptor antagonist and morphine decrease CRPS-pain and cerebral pain representation.

A combination therapy of morphine with an NMDA-receptor antagonist might be more effective than morphine without a NMDA-receptor antagonist for the relief of neuropathic pain in patients with complex regional pain syndrome (CRPS). In order to test the efficacy of this combination therapy we performed a double-blind randomized placebo-controlled study on patients suffering from CRPS of the upper extremity. We used functional magnetic resonance imaging during movement of the affected and unaffected upper hand before and after a treatment regimen of 49 days that contrasted morphine and an NMDA-receptor antagonist with morphine and placebo. We postulated superior pain relief for the combination therapy and concomitant changes in brain areas associated with nociceptive processing. Only the combination therapy reduced pain at rest and during movement, and disability. After treatment, activation in the contralateral primary somatosensory (cS1) and anterior cingulate cortex was significantly reduced when the affected hand was moved. Pain relief during therapy was related to decreased activation in cS1 and secondary somatosensory cortex (S2). Our data suggest that the combination of morphine with an NMDA-receptor antagonist significantly affects the cerebral processing of nociceptive information in CRPS. The correlation of pain relief and decrease in cortical activity in cS1 and S2 is in accordance with the expected impact of the NMDA-receptor antagonist on cerebral pain processing with emphasis on sensory-discriminative aspects of pain.

Effects of rizatriptan on the contingent negative variation in healthy women.

The effect of the antimigraine drug rizatriptan on the amplitude and habituation of the contingent negative variation (CNV) in healthy women was examined in a randomized, double-blind, placebo-controlled trial. The test persons were assigned either to a drug (n = 20) or a placebo group (n = 20). The CNV was recorded three times: before, directly after, and 24 h after drug or placebo intake. The CNV paradigm was presented in a standard, a cued and a choice version. Rizatriptan led to an increase of CNV amplitude that depended on the level of difficulty of the task. Whereas there was no drug effect in the standard version, an amplitude increase was obtained mainly in the choice task. The results are in line with the ceiling theory of migraine, which assumes a rise of CNV amplitude if the serotonin level is lowered.

Phantom movements and pain. An fMRI study in upper limb amputees.

Using functional MRI, we investigated 14 upper limb amputees and seven healthy controls during the execution of hand and lip movements and imagined movements of the phantom limb or left hand. Only patients with phantom limb pain showed a shift of the lip representation into the deafferented primary motor and somatosensory hand areas during lip movements. Displacement of the lip representation in the primary motor and somatosensory cortex was positively correlated to the amount of phantom limb pain. Thalamic activation was only present during executed movements in the healthy controls. The cerebellum showed no evidence of reorganizational changes. In amputees, movement of the intact hand showed a level of activation similar to movement of the right dominant hand in the healthy controls. During imagination of moving the phantom hand, all patients showed significantly higher activation in the contralateral primary motor and somatosensory cortices compared with imagination of hand movements in the controls. In the patients with phantom limb pain but not the pain-free amputees, imagined movement of the phantom hand activated the neighbouring face area. These data suggest selective coactivation of the cortical hand and mouth areas in patients with phantom limb pain. This reorganizational change may be the neural correlate of phantom limb pain.

The effect of opioids on phantom limb pain and cortical reorganization.

The efficacy of oral retarded morphine sulphate (MST) was tested against placebo in a double-blind crossover design in 12 patients with phantom limb pain after unilateral leg or arm amputation. Two counterbalanced treatment phases of 4 weeks each were initiated with an intravenous test infusion of MST or Placebo. The titration phase was 2 weeks. The dose of MST was titrated to at least 70 mg/day and at highest 300 mg/day. Pain intensity was assessed hourly on visual analog scales during a 4-week treatment-free phase, both treatment phases and at two follow-ups (6 and 12 months). Reorganization of somatosensory cortex, electric perception and pain thresholds as well as selective attention were measured pre- and post-treatment. A significant pain reduction was found during MST but not during placebo. A clinically relevant response to MST (pain reduction of more than 50%) was evident in 42%, a partial response (pain reduction of 25-50%) in 8% of the patients. Neuromagnetic source imaging of three patients showed initial evidence for reduced cortical reorganization under MST concurrent with the reduction in pain intensity. Perception and pain thresholds were not significantly altered whereas attention was significantly lower under MST. Thus, opioids show efficacy in the treatment of phantom limb pain and may potentially influence also cortical reorganization. These data need to be replicated in larger patient samples.

[Cortical reorganization and pain. Empirical findings and therapeutic implication using the example of phantom pain]. / Kortikale Reorganisation und Schmerz. Empirische Befunde und therapeutische Implikationen am Beispiel des Phantomschmerzes.

The neuroscientific research of the past years has shown that extensive plastic change occurs in the adult human brain. The functional reorganization of the somatosensory and motor maps related to phantom limb pain is described. Subsequent to deafferentation amputees with phantom limb pain show a shift of neighbouring representation zones into the deafferented zone of the somatosensory and motor cortex that can be detected with noninvasive neuroimaging methods. This reorganization of the sensory and motor maps is not found in painfree amputees and persons with congenital loss of a limb. We discuss a model of the development of phantom limb pain that incorporates both peripheral and central factors and assigns an important role to chronic pain before the amputation. The modulation of plasticity and phantom limb pain by anesthesiological interventions is described and the results of preemptive analgesia for the prevention of phantom limb pain are discussed. Opioid treatment and behaviorally relevant stimulation are effective means to eliminate phantom limb pain and cortical somatosensory pain memories.

[Psycho-oncologic interventions--critical review]. / Psychoonkologische Interventionen--Kritisches Review.

Following information on diagnosis, therapy and prognosis, supportive psycho-oncological interventions may be performed. General targets of psychological intervention are to help coping with disease problems and family-related problems and to reduce symptoms related to disease and therapy such as pain, anticipatory nausea and vomiting, stress, anxiety, depression and feeling of helplessness. A number of different kinds of controlled interventions may contribute significantly to both psychological and physical health outcomes in cancer patients. This review confirms the efficacy of education, individual psychotherapy, group interventions and behavioural training in reducing disease- related and therapy-related symptoms, depression and anxiety, thus improving psychological functioning and the quality of life. The multidimensional evaluation of psychooncological interventions including immunological parameters, the question of differential indication of psychological interventions in cancer patients' and the influence of psychological predictors on the course of different cancer diseases and survival rates are significant aspects that merit further research.

The cortical somatotopic map and phantom phenomena in subjects with congenital limb atrophy and traumatic amputees with phantom limb pain.

The extent of the cortical somatotopic map and its relationship to phantom phenomena was tested in five subjects with congenital absence of an upper limb, four traumatic amputees with phantom limb pain and five healthy controls. Cortical maps of the first and fifth digit of the intact hand, the lower lip and the first toe (bilaterally) were obtained using neuroelectric source imaging. The subjects with congenital upper limb atrophy showed symmetric positions of the left and right side of the lower lip and the first toe, whereas the traumatic amputees with pain showed a significant shift (about 2.4 cm) of the cortical representation of the lower lip towards the hand region contralateral to the amputation side but no shift for the toe representation. In healthy controls, no significant hemispheric differences between the cortical representation of the digits, lower lip or first toe were found. Phantom phenomena were absent in the congenital but extensive in the traumatic amputees. These data confirm the assumption that congenital absence of a limb does not lead to cortical reorganization or phantom limbs whereas traumatic amputations that are accompanied by phantom limb pain show shifts of the cortical areas adjacent to the amputation zone towards the representation of the deafferented body part.

The relationship of phantom limb pain to other phantom limb phenomena in upper extremity amputees.

In thirty-two unilateral upper extremity amputees with and without phantom limb pain, various phantom limb phenomena were investigated. In general, the incidence of non-painful phantom limb sensations was higher in patients with phantom limb pain than in pain-free amputees. Kinesthetic and kinetic phantom limb sensations were reported more frequently than exteroceptive cutaneous sensations. There was a significant positive correlation between phantom limb pain and stump pain. Patients more frequently assigned sensory than affective pain qualities to their phantom limb pain, whereas no differences between pain qualities were observed for stump pain. No support was found for a relationship between the presence of telescoping (i.e., shrinkage of the phantom limb) and phantom limb pain. These findings point to central as well as to peripheral factors contributing to phantom limb pain.

Effects of regional anesthesia on phantom limb pain are mirrored in changes in cortical reorganization.

The causes underlying phantom limb pain are still unknown. Recent studies on the consequences of nervous system damage in animals and humans reported substantial reorganization of primary somatosensory cortex subsequent to amputation, and one study showed that cortical reorganization is positively correlated with phantom limb pain. This paper examined the hypothesis of a functional relationship between cortical reorganization and phantom limb pain. Neuroelectric source imaging was used to determine changes in cortical reorganization in somatosensory cortex after anesthesia of an amputation stump produced by brachial plexus blockade in six phantom limb pain patients and four pain-free amputees. Three of six phantom limb subjects experienced a virtual elimination of current phantom pain attributable to anesthesia (mean change: 3.8 on an 11-point scale; Z = -1.83; p < 0.05) that was mirrored by a very rapid elimination of cortical reorganization in somatosensory cortex (change = 19.8 mm; t(2) = 5.60; p < 0.05). Cortical reorganization remained unchanged (mean change = 1.6 mm) in three phantom limb pain amputees whose pain was not reduced by brachial plexus blockade and in the phantom pain-free amputation controls. These findings suggest that cortical reorganization and phantom limb pain might have a causal relationship. Methods designed to alter cortical reorganization should be examined for their efficacy in the treatment of phantom limb pain.

Cortical correlates of semantic classical conditioning.

Event-related potentials to visually displayed pseudowords were registered from 13 individuals. In a differential conditioning paradigm, half of the pseudowords had previously been paired with a painful electric shock (shock words) and the other half had been presented without shock (nonshock words). Participants were asked to decide if the words had been presented during the conditioning phase or not. Larger N100 amplitudes and a more negative-going slow wave 400-800 ms after word presentation were found for shock as compared with nonshock words. This effect was stronger over the left than over the right hemisphere. This left-lateralized negativity might reflect the activation of a cell assembly representing the memory of the learned word-shock contingency. Furthermore, the increased N100 amplitude elicited by shock as compared with nonshock words may be interpreted as an increased attentive facilitation for aversive pain-related information as a consequence of conditioning.

Evidence for a change in neural processing in phantom limb pain patients.

The present study was designed to investigate differences in neural processing of pain-related semantic information in amputees with and without chronic phantom limb pain and healthy controls. One-hundred-and-twenty words (40 neutral, 40 body-related, 40 pain-related) were presented in pseudorandom order to probe group differences in the perception of pain-related information. Visual evoked potentials (VEP) to the words were recorded from 11 scalp locations, EMG was measured at the stump and the contralateral side and bilaterally from the M. corrugator. In addition, heart rate and skin conductance responses were obtained. Both early and late VEP components were altered. Pain-free amputees showed a reduced N100 amplitude compared to phantom limb pain patients and healthy controls whereas the phantom limb pain patients displayed a significantly enhanced late positivity (500-800 msec after word onset). VEP components were unaffected by word type. The peripheral EMG responses were significantly different among the groups: phantom limb pain patients showed larger EMG reactions on the stump than on the contralateral side, whereas pain-free amputees showed the opposite effect. The data suggest an enhanced central and peripheral processing of visual stimuli in phantom limb pain patients.

Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation.

Although phantom-limb pain is a frequent consequence of the amputation of an extremity, little is known about its origin. On the basis of the demonstration of substantial plasticity of the somatosensory cortex after amputation or somatosensory deafferentation in adult monkeys, it has been suggested that cortical reorganization could account for some non-painful phantom-limb phenomena in amputees and that cortical reorganization has an adaptive (that is, pain-preventing) function. Theoretical and empirical work on chronic back pain has revealed a positive relationship between the amount of cortical alteration and the magnitude of pain, so we predicted that cortical reorganization and phantom-limb pain should be positively related. Using non-invasive neuromagnetic imaging techniques to determine cortical reorganization in humans, we report a very strong direct relationship (r = 0.93) between the amount of cortical reorganization and the magnitude of phantom limb pain (but not non-painful phantom phenomena) experienced after arm amputation. These data indicate that phantom-limb pain is related to, and may be a consequence of, plastic changes in primary somatosensory cortex.

Extensive reorganization of the somatosensory cortex in adult humans after nervous system injury.

Magnetic source imaging revealed that the topographic representation in the somatosensory cortex of the face area in upper extremity amputees was shifted an average of 1.5 cm toward the area that would normally receive input from the now absent nerves supplying the hand and fingers. Observed alterations provide evidence for extensive plastic reorganization in the adult human cortex following nervous system injury, but they are not a sufficient cause of the phantom phenomenon termed 'facial remapping'.

Effects of PRES baroreceptor stimulation on thermal and mechanical pain threshold in borderline hypertensives and normotensives.

Prior studies have noted a pain relieving effect of baroreceptor stimulation and of higher tonic blood pressure in animals and humans. The present study used a new technique for the controlled, noninvasive stimulation of human carotid baroreceptors (PRES). PRES baroreceptor manipulation was delivered to both normotensive subjects (n = 11) and medication-free labile hypertensive subjects (n = 10) during both thermal and mechanical pain. Consistent with prior research, hypertensives had a higher threshold for thermal pain than did normotensives. PRES baroreceptor manipulation had no significant effect on thermal pain threshold for either group. For the mechanical pain model, the opposite results were obtained; group pain thresholds did not differ, but there was a significant PRES baroreceptor stimulation effect of increasing pain threshold for both groups. Results are discussed in terms of specific features of the stimuli, dampening of pain in hypertensives, and adaptation to pain.

Cigarette smoking, blood lipids, and baroreceptor-modulated nociception.

Activation of arterial blood pressure has been shown to influence higher central nervous activity. In animals, induction of sleep-like states and increases of seizure and pain thresholds in response to baroreceptor stimulation have been reported. In certain human groups, mechanical stimulation of the carotid baroreceptors also increases pain thresholds. The present paper examines the hypothesis that smokers show baroreceptor dependent antinociception as compared to non-smokers. It is speculated that one effect which rewards smoking is the nicotine induced phasic blood pressure increase which leads to baroreceptor stimulation and dampens pain perception. One hundred and twenty subjects were investigated using a recently developed mechanical baroreceptor stimulation technique and an electrical pain stimulus. The group of heavy smokers showed the predicted effect: their pain thresholds were enhanced during conditions of increased baroreceptor activity as compared to the control condition. The group of medium, light and non-smokers, however, did not show this effect. Neither blood lipid levels nor diastolic or systolic blood pressure paralleled the group differences on baroreceptor dependent antinociception. In heavy smokers, the nicotine induced phasic blood pressure increases might have baroreceptor dependent pain dampening effects, which might be among the reinforcing qualities of smoking.

Biofeedback of visual evoked potentials.

The present study investigated the operant conditioning of visual evoked potentials within a latency range between 200 and 600 ms using a visual discrimination task, and scrutinized whether biofeedback-induced potential shifts covaried with behavioral responses (reaction time, RT). It could be demonstrated that subjects were able to modify their ERPs towards more or less positivity according to the instruction given. In addition, in could be shown that a biofeedback-induced greater positivity of the P300-complex was highly correlated with a decrease of reaction time. It is hypothesized that this could be due to a modification of P300-components reflecting information processing.