Marcel Franz

Differential processing of laser stimuli by Aδ and C fibres in major depression

&NA; Clinical studies have revealed that up to 92% of major depressed patients report pain complaints such as back or abdominal pain. Furthermore, patients suffering from depression exhibit increased superficial pain thresholds and decreased ischemic (deep) pain thresholds during experimental pain testing in comparison to healthy controls. Here, we aimed to investigate a putative role of Aδ‐ and C‐fibre activation in altered pain perception in the disease. Laser‐evoked potentials (LEPs) of 27 unmedicated depressed patients and 27 matched controls were recorded. Aδ and C fibres were activated separately. Amplitudes and latencies of N2 and P2 peaks of Aδ‐ (Aδ‐LEP) and C‐fibre‐ (C‐LEP) related LEPs were evaluated. Depressed patients showed significantly decreased Aδ‐LEP amplitudes (N2 peak: P = 0.019; P2 peak: P = 0.024) and delayed C‐LEP latencies (P2 peak: P = 0.0495; N2 peak: P = 0.0556). In contrast, C‐LEP amplitudes and Aδ‐LEP latencies were unaffected. Our results might be suggestive of the differential impact of physiological changes on pain processing in depression. Thus, Aδ‐LEP might reflect the physiological correlate of the augmented superficial pain thresholds during depression. On the contrary, the C‐fibre component mediates the facets of pain processing, outlasting the stimulation period, and has been shown to be exaggerated in chronic pain states. Therefore, the functional over‐representation of the C‐fibre component found in our study might be a possible link between depression and associated pain complaints. Laser‐evoked potentials of depressed patients and controls were recorded. Results suggest a differential impact of physiological changes of the disease on pain processing.

Laser heat stimulation of tiny skin areas adds valuable information to quantitative sensory testing in postherpetic neuralgia

Summary Patients with postherpetic neuralgia are severely impaired to recognize laser stimuli applied to tiny skin areas (LTA). LTA sensitivity and specificity was higher than thermal quantitative sensory testing. Abstract Patients suffering from postherpetic neuralgia often complain about hypo‐ or hypersensation in the affected dermatome. The loss of thermal sensitivity has been demonstrated by quantitative sensory testing as being associated with small‐fiber (Aδ‐ and C‐fiber) deafferentation. We aimed to compare laser stimulation (radiant heat) to thermode stimulation (contact heat) with regard to their sensitivity and specificity to detect thermal sensory deficits related to small‐fiber dysfunction in postherpetic neuralgia. We contrasted detection rate of laser stimuli with 5 thermal parameters (thresholds of cold/warm detection, cold/heat pain, and sensory limen) of quantitative sensory testing. Sixteen patients diagnosed with unilateral postherpetic neuralgia and 16 age‐ and gender‐matched healthy control subjects were tested. Quantitative sensory testing and laser stimulation of tiny skin areas were performed in the neuralgia‐affected skin and in the contralateral homologue of the neuralgia‐free body side. Across the 5 thermal parameters of thermode stimulation, only one parameter (warm detection threshold) revealed sensory abnormalities (thermal hypoesthesia to warm stimuli) in the neuralgia‐affected skin area of patients but not in the contralateral area, as compared to the control group. In contrast, patients perceived significantly less laser stimuli both in the affected skin and in the contralateral skin compared to controls. Overall, laser stimulation proved more sensitive and specific in detecting thermal sensory abnormalities in the neuralgia‐affected skin, as well as in the control skin, than any single thermal parameter of thermode stimulation. Thus, laser stimulation of tiny skin areas might be a useful diagnostic tool for small‐fiber dysfunction.

Somatosensory spatial attention modulates amplitudes, latencies, and latency jitter of laser-evoked brain potentials.

Several studies provided evidence that the amplitudes of laser-evoked potentials (LEPs) are modulated by attention. However, previous reports were based on across-trial averaging of LEP responses at the expense of losing information about intertrial variability related to attentional modulation. The aim of this study was to investigate the effects of somatosensory spatial attention on single-trial parameters (i.e., amplitudes, latencies, and latency jitter) of LEP components (N2 and P2). Twelve subjects participated in a sustained spatial attention paradigm while noxious laser stimuli (left hand) and noxious electrical stimuli (right hand) were sequentially delivered to the dorsum of the respective hand with nonnoxious air puffs randomly interspersed within the sequence of noxious stimuli. Participants were instructed to mentally count all stimuli (i.e., noxious and nonnoxious) applied to the attended location. Laser stimuli, presented to the attended hand (ALS), elicited larger single-trial amplitudes of the N2 component compared with unattended laser stimuli (ULS). In contrast, single-trial amplitudes of the P2 component were not significantly affected by spatial attention. Single-trial latencies of the N2 and P2 were significantly smaller for ALS vs. ULS. Additionally, the across-trial latency jitter of the N2 component was reduced for ALS. Conversely, the latency jitter of the P2 component was smaller for ULS compared with ALS. With the use of single-trial analysis, the study provided new insights into brain dynamics of LEPs related to spatial attention. Our results indicate that single-trial parameters of LEP components are differentially modulated by spatial attention.

Laser heat hyperalgesia is not a feature of non-specific chronic low back pain.

Based upon studies using mechanical pin‐prick, pressure, electrical or heat stimuli applied to painful and/or pain‐free parts of the body, chronic low back pain (CLBP) has been shown to be associated with generalized and enhanced pain sensitivity and altered brain responses to noxious stimuli. To date, no study examined the processing of noxious laser heat pulses, which are known to selectively excite thermal nociceptors located in the superficial skin layers, in CLBP.

Human Brain Stem Structures Respond Differentially to Noxious Heat

Concerning the physiological correlates of pain, the brain stem is considered to be one core region that is activated by noxious input. In animal studies, different slopes of skin heating (SSH) with noxious heat led to activation in different columns of the midbrain periaqueductal gray (PAG). The present study aimed at finding a method for differentiating structures in PAG and other brain stem structures, which are associated with different qualities of pain in humans according to the structures that were associated with different behavioral significances to noxious thermal stimulation in animals. Brain activity was studied by functional MRI in healthy subjects in response to steep and shallow SSH with noxious heat. We found differential activation to different SSH in the PAG and the rostral ventromedial medulla (RVM). In a second experiment, we demonstrate that the different SSH were associated with different pain qualities. Our experiments provide evidence that brainstem structures, i.e., the PAG and the RVM, become differentially activated by different SSH. Therefore, different SSH can be utilized when brain stem structures are investigated and when it is aimed to activate these structures differentially. Moreover, percepts of first pain were elicited by shallow SSH whereas percepts of second pain were elicited by steep SSH. The stronger activation of these brain stem structures to SSH, eliciting percepts of second vs. first pain, might be of relevance for activating different coping strategies in response to the noxious input with the two types of SSH.

Enhanced Brain Responses to Pain-Related Words in Chronic Back Pain Patients and Their Modulation by Current Pain

Previous functional magnetic resonance imaging (fMRI) studies in healthy controls (HC) and pain-free migraine patients found activations to pain-related words in brain regions known to be activated while subjects experience pain. The aim of the present study was to identify neural activations induced by pain-related words in a sample of chronic back pain (CBP) patients experiencing current chronic pain compared to HC. In particular, we were interested in how current pain influences brain activations induced by pain-related adjectives. Subjects viewed pain-related, negative, positive, and neutral words; subjects were asked to generate mental images related to these words during fMRI scanning. Brain activation was compared between CBP patients and HC in response to the different word categories and examined in relation to current pain in CBP patients. Pain-related words vs. neutral words activated a network of brain regions including cingulate cortex and insula in subjects and patients. There was stronger activation in medial and dorsolateral prefrontal cortex (DLPFC) and anterior midcingulate cortex in CPB patients than in HC. The magnitude of activation for pain-related vs. negative words showed a negative linear relationship to CBP patients’ current pain. Our findings confirm earlier observations showing that pain-related words activate brain networks similar to noxious stimulation. Importantly, CBP patients show even stronger activation of these structures while merely processing pain-related words. Current pain directly influences on this activation.

Captured by the pain: pain steady-state evoked potentials are not modulated by selective spatial attention.

Attention has been shown to affect the neural processing of pain. However, the exact mechanisms underlying this modulation remain unknown. Here, we used a new method called pain steady-state evoked potentials (PSSEPs) to investigate whether selective spatial attention affects EEG responses to tonic painful stimuli. In general, steady-state evoked potentials reflect changes in the EEG spectrum at a certain frequency that correspond to the frequency of a train of applied stimuli. In this study, high intensity transcutaneous electrical stimulation was delivered to both hands simultaneously with 31 Hz and 37 Hz, respectively. Subject׳s attention was directed to one of the two trains of stimulation in order to detect a small gap that was occasionally interspersed into the stimulus trains. Thereby, they had to ignore the stimulation applied to the other hand. Results show that PSSEPs were induced at 31 Hz and 37 Hz at frontal and central electrodes. PSSEPs occurred contralaterally to the respective hand stimulated with that frequency. Surprisingly, the magnitude of PSSEPs was not modulated by spatial attention towards one of the two stimuli. Our results indicate that attention can hardly be shifted between two simultaneously applied tonic painful stimulations.

Brain activity for visual judgment of lifted weight

It is well established that humans can recognize high-level aspects from point-light biological motion, such as gender and mood. If the task is to judge the manipulated weight we expected that sensorimotor regions should be recruited in the brain. Moreover, we have recently shown that chronic pain in a limb that is involved in the presented movement disturbs the weight judgment. We therefore hypothesized that some cortical regions usually activated during the processing of pain will also be activated while viewing point-light biological motion with the instruction to judge the manipulated weights. We investigated point-light biological motion of two types of movements performed with different weights in a blocked fMRI experiment in healthy subjects. In line with our a priori hypothesis, we found strong activity in the regions known as the neuromatrix of pain, such as the anterior cingulate (ACC), insula, as well as primary and secondary somatosensory regions. We also found activation in the occipital and temporal regions that are typical for biological motion, as well as regions in the cerebellum and prefrontal cortex. The activation of the somatosensory regions probably serves the judgment of the biological motion stimuli. Activation of the anterior cingulate and the insula might be explained by their role in the integration of behaviorally relevant information. Alternatively, these structures are known to be involved in the processing of nociceptive information and pain. So it seems possible that the interference between judgment of weights and perception of pain in chronic pain patients occurs in the somatosensory areas, anterior cingulate and/or insula. This finding provides important information as to the underlying mechanisms used for the weight judgment task, but also why chronic pain interferes with this task.

Effects of Temporary Functional Deafferentation in Chronic Stroke Patients: Who Profits More?

Temporary functional deafferentation (TFD) by an anesthetic cream on the stroke-affected forearm was shown to improve sensorimotor abilities of stroke patients. The present study investigated different predictors for sensorimotor improvements during TFD and indicated outcome differences between patients grouped in subcortical lesions only and lesions with any cortical involvement. Thirty-four chronic stroke patients were temporarily deafferented on the more affected forearm by an anesthetic cream. Somatosensory performance was assessed using von Frey Hair and grating orientation task; motor performance was assessed by a shape-sorter-drum task. Seven potential predictors were entered into three linear multiple regression models. Furthermore, effects of TFD on outcome variables for the two groups (cortical versus subcortical lesion) were compared. Sex and sensory deficit were significant predictors for changes in motor function while age accounted for changes in grating orienting task. Males, patients with a stronger sensory deficit, and older patients profited more. None of the potential predictors made significant contributions to changes in threshold for touch. Furthermore, there were no differences in sensorimotor improvement between lesion site groups. The effects of TFD together with the low predictability of the investigated parameters suggest that characteristics of patients alone are not suitable to exclude some patients from TFD.

Are There Abnormalities in Peripheral and Central Components of Somatosensory Evoked Potentials in Non-Specific Chronic Low Back Pain?

Chronic low back pain (CLBP) was shown to be associated with longer reflex response latencies of trunk muscles during external upper limb perturbations. One theoretical, but rarely investigated possibility for longer reflex latencies might be related to modulated somatosensory information processing. Therefore, the present study investigated somatosensory evoked potentials (SEPs) to median nerve stimulation in CLBP patients and healthy controls (HC). Latencies of the peripheral N9 SEP component were used as the primary outcome. In addition, latencies and amplitudes of the central N20 SEP component, sensory thresholds, motor thresholds and nerve conduction velocity were also analyzed in CLBP patients and HC. There is a trend for the CLBP patients to exhibit longer N9 latencies at the ipsilateral Erb’s point compared to HC. This trend is substantiated by significantly longer N9 latencies in CLBP patients compared to normative data. None of the other parameters showed any significant difference between CLBP patients and HC. Overall, our data indicate small differences of the peripheral N9 SEP component; however, these differences cannot explain the reflex delay observed in CLBP patients. While it was important to rule out the contribution of early somatosensory processing and to elucidate its contribution to the delayed reflex responses in CLBP patients, further research is needed to find the primary source(s) of time-delayed reflexes in CLBP.