Use your imagination: training the brain and not the body to improve chronic pain and restore function.
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Biofeedback, Psychology↗
Biomedical subjects
Christian Maihöfner
Publications and source records attributed to Christian Maihöfner.
Spontaneous magnetoencephalographic activity in patients with obsessive-compulsive disorder.
Non-invasive functional imaging techniques have begun to delineate the underlying neurophysiological basis of obsessive-compulsive disorder (OCD). In the present study, we investigated slow (2-6 Hz) and fast (12.5-30 Hz) spontaneous magnetoencephalographic (MEG) activity in ten patients with obsessive-compulsive disorders compared to ten healthy control subjects. Fast MEG activity was significantly elevated in OCD patients. The corresponding dipole density maxima were concentrated on the left superior temporal gyrus. Although no differences were detected in the absolute dipole numbers between controls and OCD patients regarding slow MEG activity, only the latter showed a clustering of slow MEG activity over their left dorsolateral prefrontal cortex. We conclude that alterations of spontaneous MEG activity in prefrontal and temporal cortices may be linked to the pathogenesis of OCD. Therefore, we provide further functional neuroimaging evidence that the complex features of OCD have neural correlates, which may help in a future understanding of this disease.
Adult↗
Mislocalization of tactile stimulation in patients with complex regional pain syndrome.
Complex-Regional-Pain-Syndromes (CRPS) are characterized by sensory,motor and autonomic dysfunctions. Patterns of sensory symptoms suggest changes within the central nervous system (CNS). Recently, we could show substantial reorganization of somatotopic maps within the central nervous system of patients with CRPS using functional imaging techniques (Maihofner et al. Neurology, 2003). These changes were predicted by CRPS pain and mechanical hyperalgesia. In the present study we looked for potential psychophysical correlates of cortical reorganization in CRPS. Sequential pneumatic non-noxious tactile stimulation was performed at digits 1 and 5 in 24 patients with CRPS of the upper extremities. Both the unaffected and affected side were examined. Patients were interviewed for tactile induced sensations. The occurrence of mislocalizations was correlated with a detailed psychophysical examination in which sensory, motor and autonomic symptoms were assessed. Eight patients (30 %) reported tactile mislocalizations, which were felt in the affected hand. In four cases the referred sensations spread into other nerve territories (ulnar/median nerve). Presence of mechanical hyperalgesia significantly predicted the occurrence of mislocalizations. In contrast, in a healthy control group, no mislocalizations were found. Thus, our results further support the concept of pain-induced reorganization in the somatosensory system of CRPS patients.
Adult↗
Functional imaging of allodynia in complex regional pain syndrome.
OBJECTIVE: To investigate cerebral activations underlying touch-evoked pain (dynamic-mechanical allodynia) in patients with neuropathic pain. METHODS: fMRI was used in 12 patients with complex regional pain syndromes (CRPSs). Allodynia was elicited by gently brushing the affected CRPS hand. Elicited pain ratings were recorded online to obtain pain-weighted predictors. Both activations and deactivations of blood oxygenation level-dependent signals were investigated. RESULTS: Nonpainful stimulation on the nonaffected hand activated contralateral primary somatosensory cortex (S1), bilateral insula, and secondary somatosensory cortices (S2). In contrast, allodynia led to widespread cerebral activations, including contralateral S1 and motor cortex (M1), parietal association cortices (PA), bilateral S2, insula, frontal cortices, and both anterior and posterior parts of the cingulate cortex (aACC and pACC). Deactivations were detected in the visual, vestibular, and temporal cortices. When rating-weighted predictors were implemented, only few activations remained (S1/PA cortex, bilateral S2/insular cortices, pACC). CONCLUSIONS: Allodynic stimulation recruits a complex cortical network. Activations include not only nociceptive but also motor and cognitive processing. Using a covariance approach (i.e., implementation of rating-weighted predictors) facilitates the detection of a neuronal matrix involved in the encoding of allodynia. The pattern of cortical deactivation during allodynia may hint at a shift of activation from tonically active sensory systems, like visual and vestibular cortices, into somatosensory-related brain areas.
Adult↗
Secondary somatosensory cortex is important for the sensory-discriminative dimension of pain: a functional MRI study.
A complex cortical network is believed to encode the multidimensionality of the human pain experience. In the present study, we used functional magnetic resonance imaging (fMRI) to examine whether the brain's processing of noxious stimuli differs with different psychophysical properties. Painful mechanical impact and heat stimulations of equal stimulus intensity were applied to the forearm of 14 subjects in a randomized order. Concomitantly, subjects had to evaluate the corresponding sensory-discriminative and affective-motivational pain dimensions. fMRI revealed an increased activation of bilateral secondary somatosensory cortices (S2) during mechanical impact pain compared with heat pain. Activations in S2 were significantly correlated with scores for the sensory-discriminative component during mechanical impact pain. By contrast, corresponding scores for the affective-motivational pain dimension did not differ between both conditions. In summary, we conclude that S2 plays an important role in the sensory-discriminative dimension of pain.
Adult↗
Effects of repetitive transcranial magnetic stimulation in depression: a magnetoencephalographic study.
Recently, repetitive transcranial magnetic stimulation has evolved as a potential therapeutic tool to interfere with brain changes associated with neurological and psychiatric diseases. Little is known about its mode of action, however. Here, we investigated effects of repetitive transcranial magnetic stimulation on spontaneous magnetoencephalographic activity in patients with major depression. Before treatment, depressed patients showed a significant increase in slow magnetoencephalographic activity (2-6 Hz) over the left prefrontal cortex, compared with healthy controls. This activity significantly decreased during 10 days of repetitive transcranial magnetic stimulation, paralleled by clinical improvement. We conclude that therapeutic repetitive transcranial magnetic stimulation effects can be mirrored by changes of spontaneous magnetoencephalographic activity.
Adult↗
Differential coding of hyperalgesia in the human brain: a functional MRI study.
Neuropathic pain can be both ongoing or stimulus-induced. Stimulus-induced pain, also known as hyperalgesia, can be differentiated into primary and secondary hyperalgesia. The former results from sensitization of peripheral nociceptive structures, the latter involves sensitization processes within the central nervous system (CNS). Hypersensitivity towards heat stimuli, i.e. thermal hyperalgesia, is a key feature of primary hyperalgesia, whereas secondary hyperalgesia is characterized by hypersensitivity towards mechanical (e.g. pin-prick) stimulation. Using functional magnetic resonance imaging (fMRI), we investigated if brain activation patterns associated with primary and secondary hyperalgesia might differ. Thermal and pin-prick hyperalgesia were induced on the left forearm in 12 healthy subjects by topical capsaicin (2.5%, 30 min) application. Equal pain intensities of both hyperalgesia types were applied during fMRI experiments, based on previous quantitative sensory testing. Simultaneously, subjects had to rate the unpleasantness of stimulus-related pain. Pin-prick hyperalgesia (i.e. subtraction of brain activations during pin-prick stimulation before and after capsaicin exposure) led to activations of primary and secondary somatosensory cortices (S1 and S2), associative-somatosensory cortices, insula and superior and inferior frontal cortices (SFC, IFC). Brain areas activated during thermal hyperalgesia (i.e. subtraction of brain activations during thermal stimulation before and after capsaicin exposure) were S1 and S2, insula, associative-somatosensory cortices, cingulate cortex (GC), SFC, middle frontal cortex (MFC) and IFC. When compared to pin-prick hyperalgesia, thermal hyperalgesia led to an increased activation of bilateral anterior insular cortices, MFC, GC (Brodmann area 24' and 32') and contralateral SFC and IFC, despite equal pain intensities. Interestingly, stronger activations of GC, contralateral MFC and anterior insula significantly correlated to higher ratings of the stimulus-related unpleasantness. We conclude that thermal and mechanical hyperalgesia produce substantially different brain activation patterns. This is linked to different psychophysical properties.
Adult↗
Transient tetraplegia after cervical facet joint injection for chronic neck pain administered without imaging guidance.
We report about a patient in whom transient tetraplegia with intact proprioception occurred immediately after infiltration of a facet joint at the C6 level guided by anatomical landmarks. After positioning the patient supine and applying atropine and oxygen, respiration and circulation were stable and all symptoms resolved within the next 30 min. The type of neurological pattern and the course of disease suggest an inadvertent injection into a cervical radicular artery that reinforces the anterior spinal artery. This complication is potentially serious and may be permanently disabling or life threatening. It should be considered by any clinician performing "blind" zygapophysial joint injections in the cervical spine. Using imaging guidance should help prevent this type of complication.
Adult↗
Mechanical hyperalgesia in complex regional pain syndrome: a role for TNF-alpha?
Plasma concentrations of soluble tumor necrosis factor alpha (TNF-alpha) receptor type I (sTNF-RI) were assessed in two complex regional pain syndrome (CRPS) patient groups (n = 30 and n = 16) and healthy controls (n = 25). Patients with CRPS and mechanical hyperalgesia had higher levels of sTNF-RI (1,661.8 +/- 146.8 pg/mL) compared with those with CRPS with identical clinical appearance but without hyperalgesia (1,155.9 +/- 56.3 pg/mL) and controls (1,239.5 +/- 42.9 pg/mL). This study suggests involvement of TNF-alpha in mechanical hyperalgesia of CRPS.
Adult↗
TRPA1 and TRPM8 activation in humans: effects of cinnamaldehyde and menthol.
The aim of this study was to evaluate the psychophysical effects of both TRPA1 and TRPM8 activation in humans by application of either cinnamaldehyde or menthol. We applied 10% cinnamaldehyde or 40% menthol solutions on the forearm in 10 study participants. Quantitative sensory testing and laser Doppler imaging was performed before and after exposure to the compounds. Cinnamaldehyde evoked significant spontaneous pain and induced heat and mechanical hyperalgesia, cold hypoalgesia and a neurogenic axon reflex erythema. In contrast, TRPM8 activation by menthol produced no axon reflex reaction and resulted in cold hyperalgesia. We conclude that agonists of TRPA1 and TRPM8 channels produce strikingly different psychophysical patterns.
Acrolein↗
Brain processing during mechanical hyperalgesia in complex regional pain syndrome: a functional MRI study.
Complex Regional Pain Syndromes (CRPS) are characterized by a triad of sensory, motor and autonomic dysfunctions of still unknown origin. Pain and mechanical hyperalgesia are hallmarks of CRPS. There are several lines of evidence that central nervous system (CNS) changes are crucial for the development and maintenance of mechanical hyperalgesia. However, little is known about the cortical structures associated with the processing of hyperalgesia in pain patients. This study describes the use of functional magnetic resonance imaging (fMRI) to delineate brain activations during pin-prick hyperalgesia in CRPS. Twelve patients, in whom previous quantitative sensory testing revealed the presence of hyperalgesia to punctuate mechanical stimuli (i.e. pin-prick hyperalgesia), were included in the study. Pin-prick-hyperalgesia was elicited by von-Frey filaments at the affected limb. For control, the identical stimulation was performed on the unaffected limb. fMRI was used to explore the corresponding cortical activations. Mechanical stimulation at the unaffected limb was non-painful and mainly led to an activation of the contralateral primary somatosensory cortex (S1), insula and bilateral secondary somatosensory cortices (S2). The stimulation of the affected limb was painful (mechanical hyperalgesia) and led to a significantly increased activation of the S1 cortex (contralateral), S2 (bilateral), insula (bilateral), associative-somatosensory cortices (contralateral), frontal cortices and parts of the anterior cingulate cortex. The results of our study indicate a complex cortical network activated during pin-prick hyperalgesia in CRPS. The underlying neuronal matrix comprises areas not only involved in nociceptive, but also in cognitive and motor processing.
Adult↗
Cortical reorganization during recovery from complex regional pain syndrome.
OBJECTIVE: To characterize reorganization of the primary somatosensory cortex (S1) during healing process in complex regional pain syndrome (CRPS). BACKGROUND: Recently, the authors showed extensive reorganization of the S1 cortex contralateral to the CRPS affected side. Predictors for these plastic changes were CRPS pain and the extent of mechanical hyperalgesia. It is unclear how these S1 changes develop following successful therapy. METHODS: The authors used magnetic source imaging to explore changes in the cortical representation of digits (D) 1 and 5 in relation to the lower lip on the unaffected and affected CRPS side in 10 patients during a year or more of follow-up. RESULTS: Cortical reorganization reversed coincident with clinical improvement. A reduction of CRPS pain correlated with recovery from cortical reorganization. CONCLUSIONS: Changes of the somatotopic map within the S1 cortex may depend on CRPS pain and its recovery.
Adult↗
Cortical activity associated with auditory hallucinations.
Auditory hallucinations are one the most enigmatic and hampering symptoms associated with schizophrenia. Non-invasive functional imaging techniques have begun to delineate the underlying neuronal basis. We investigated the spontaneous magnetoencephalographic activity in a 33-year-old male schizophrenic patient and compared the results to those obtained from 13 healthy controls. Despite current neuroleptic medication (clozapine) the patient was still suffering from auditory hallucinations. Using the dipole density method, we were able to demonstrate an increase of fast MEG activity (12.5-30 Hz) in the left auditory cortex associated with hallucinations. This activity was absent in healthy controls. We conclude that an increase in fast MEG activity in the auditory cortex is a neurophysiologic correlate for auditory hallucinations in schizophrenia.
Adult↗
Selective vulnerability in amyotrophic lateral sclerosis: no evidence for a contribution of annexins, a family of calcium binding proteins.
Clinically, amyotrophic lateral sclerosis (ALS) usually presents as a pure motor system disorder, whereas oculomotor and sphincter muscle control of the anus and the bladder appear to be spared. Previously, a lacking expression of calcium binding proteins (CBPs) was demonstrated in vulnerable motor neurons in contrast to spared neuronal populations, e.g., the motor neurons of the cranial nerve III (NO) and the Onufrowicz nucleus (ON), suggesting a potential role of CBPs in the selective motoneuronal vulnerability in ALS. The annexins comprise a multigene family of CBPs, constituting a significant amount of total cellular protein and presumably involved in calcium-homeostasis and intracellular calcium-regulated pathways. We immunohistochemically investigated the expression patterns of annexins A1, A2, A4, A5, A6, and A7 in spinal cord and midbrain tissues from 24 ALS patients and 5 age-matched controls to test the hypothesis that annexins also contribute to the selective vulnerability in ALS. There was no difference in the expression patterns of ALS cases and normal controls. Annexin A1 was expressed in ependymal cells and motor neurons. Annexin A2 could be detected in ependymal and endothelial cells and motor neurons. Annexins A4 and A5 were found in both ependymal and glial cells, whereas annexin A6 was strongly expressed in motor neurons. Annexin A7 was totally absent from central nervous system tissue. A contribution of annexins to the selective vulnerability in ALS could not be derived from our results.
Adult↗
Neural activation during experimental allodynia: a functional magnetic resonance imaging study.
Abstract Pain induced by gentle stroking, i.e. dynamic-mechanical allodynia, is one of the most distressing symptoms of neuropathic pain. The underlying neuronal pathways are still a matter of debate. Here, we investigated the cortical activations associated with dynamic-mechanical allodynia in an experimental human pain model by functional magnetic resonance imaging (fMRI). Large and stable areas of brush-evoked allodynia were induced in 11 healthy subjects by topical capsaicin (2.5%, 30 min) application following local heating (45 degrees C for 5 min), thus combining both physical and chemical sensitization. During the fMRI experiments, allodynia was rekindled by local heat application (40 degrees C for 5 min) immediately before the allodynia testing. Brushing the untreated forearm (control condition) led to activations of the contralateral primary somatosensory cortex (S1), contralateral parietal association cortex (PA), bilateral secondary somatosensory cortices (S2) and insula (contralateral). Brushing the allodynic skin was painful and the cortical responses were partially overlapping with those induced by the nonpainful brush stimulation. Additionally, the contralateral inferior frontal cortex (IFC) and the ipsilateral insula were activated. Direct comparison between nonpainful brushing and brush-evoked allodynia revealed significant increases in blood oxygenation level-dependent (BOLD) signals in contralateral S1, PA, IFC and bilateral S2/insula during allodynia. This study highlights the importance of a cortical network comprising S1, PA, S2/insula and IFC in the processing of dynamic-mechanical allodynia in the human brain. Furthermore, it demonstrates that the combined heat/capsaicin model can be used successfully in the exploration of brain processes underlying stimulus-evoked pain.
Adult↗
Patterns of cortical reorganization in complex regional pain syndrome.
OBJECTIVE: To use magnetoencephalography to assess possible cortical reorganization in the primary somatosensory cortex (S1) of patients with complex regional pain syndrome (CRPS). BACKGROUND: Patterns of pain and sensory symptoms in CRPS may indicate plastic changes of the CNS. METHODS: Magnetic source imaging was used to explore changes in the cortical representation of digits (D) 1 and 5 in relation to the lower lip on the unaffected and affected CRPS side in 12 patients. RESULTS: The authors found a significant shrinkage of the extension of the cortical hand representation for the CRPS affected side. The center of the hand was shifted toward the cortical representation of the lip. The cortical reorganization correlated with the amount of CRPS pain (r = 0.792), as measured by the McGill questionnaire, and the extent of mechanical hyperalgesia (r = 0.860). Using multiple regression analysis, the best predictor for the plastic changes was found to be mechanical hyperalgesia. Additionally, S1 sources following tactile stimulation were significantly increased on the CRPS side compared to the unaffected limb. CONCLUSIONS: This study showed reorganization of the S1 cortex contralateral to the CRPS affected side. The reorganization appeared to be linked to complaints of neuropathic pain.
Adult↗
Cortical processing of brush-evoked allodynia.
The cortical processing of allodynia (touch-evoked pain) resulting from neuralgia of the lateral cutaneous femoral nerve was investigated with a newly designed pneumatically driven brush by means of magnetoencephalography. Brushing the unaffected thigh produced subsequent activation of the contralateral primary somatosensory cortex (S1) with peak latencies of 37 and 56 ms. Brushing the affected side led to comparable activation of the contralateral S1 cortex. In addition, the magnetic fields were stronger, and the corresponding equivalent current dipoles were located more laterally, consistent with the presence of cortical reorganisation. Allodynia was also accompanied by an activation of the cingulate cortex, occurring only 92 ms. after stimulus onset, an observation suggesting an Abeta-fiber-mediated neuronal pathway involved in dynamic mechanical allodynia. This study corroborates the concept of cortical reorganisation underlying chronic pain. Furthermore, it demonstrates that a remarkable early activation of the cingulate cortex may be involved in the cortical processing of allodynia.
Cerebral Cortex↗
Expression and localization of cyclooxygenase-1 and -2 in human sporadic amyotrophic lateral sclerosis.
Prostaglandins (PGs) are critical mediators of physiologic processes and inflammation. They are produced by two different isoforms of the cyclooxygenase (COX) enzyme, namely COX-1 and COX-2. In particular COX-2 was demonstrated to be crucial for PG-synthesis in inflammation. Recently, inhibition of COX-2 was shown to prevent the loss of motor neurons in a model of amyotrophic lateral sclerosis (ALS). Furthermore, spinal COX-2 expression was shown to be increased in transgenic mice that produce an ALS-like syndrome. Therefore, we investigated the expression of COX-1 and COX-2 in the spinal cord of seven human sporadic ALS patients by means of immunohistochemistry. Specimens from seven patients without any neurological disease served as controls. COX-2 expression was dramatically increased in the spinal cord of patients with ALS. Its protein was found in motor neurons, interneurons and glial cells. Statistical analysis showed a significantly higher expression of COX-2 in ALS for both neurons and glia. In contrast, COX-1 expression was predominantly confined to microglia and no apparent difference was detected between controls and ALS. In addition, we studied the concentration of prostaglandin E2 (PG E2) as a marker for COX activity in the cerebrospinal fluid of nine patients diagnosed for ALS and compared the results with those from nine patients without motor neuron disease. PG E2 levels were markedly increased in ALS cases (45.8 +/- 35.1 pg/mL) compared to the non-ALS specimens (15.8 +/- 3.7 pg/mL). The results of our study corroborate a potential role for COX-2 in the pathogenesis of motor neuron death in ALS. Selective COX-2 inhibition might therefore offer a new possibility in the treatment of human ALS. However, to determine the exact role of COX-2 in human ALS will require further research.
Aged↗