Alexander Ritter

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.

Pain-Related and Negative Semantic Priming Enhances Perceived Pain Intensity

BACKGROUND Negative affective and pain-related cues, such as pictures or words, have been shown to act as primes and enhance the perceived intensity of subsequent painful events. For pain-related semantic primes, it remains unclear whether this effect depends on negative valence itself or, specifically, on the pain-relatedness of the words. OBJECTIVES To investigate the effect of pain-related, negative affective (pain-unrelated) and neutral semantic primes on the perception of subsequent noxious target stimuli. METHODS Pain ratings in response to noxious electrical stimulation of light and moderate intensity were examined in 39 healthy subjects after subjects were exposed to semantic primes of different meaning and valence (pain-related, negative, positive and neutral adjectives) presented with different interstimulus intervals (0 ms, 500 ms and 1500 ms). RESULTS Increased pain ratings of noxious stimuli were observed following pain-related and negative compared with neutral primes. DISCUSSION The results support the motivational priming theory for semantic stimuli, indicating that affectively negative semantic primes increase subjective pain intensity. However, a specific pain-related priming effect was not reliably demonstrated. Additionally, it is shown that experimental parameters (ie, stimulus intensity and interstimulus interval) modify the extent of negative and pain-related semantic priming. CONCLUSIONS Verbal priming plays a role for the perception of noxious stimuli in a time-dependent manner.

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.

Boosting the Motor Outcome of the Untrained Hand by Action Observation: Mirror Visual Feedback, Video Therapy, or Both Combined—What Is More Effective?

Action observation (AO) allows access to a network that processes visuomotor and sensorimotor inputs and is believed to be involved in observational learning of motor skills. We conducted three consecutive experiments to examine the boosting effect of AO on the motor outcome of the untrained hand by either mirror visual feedback (MVF), video therapy (VT), or a combination of both. In the first experiment, healthy participants trained either with MVF or without mirror feedback while in the second experiment, participants either trained with VT or observed animal videos. In the third experiment, participants first observed video clips that were followed by either training with MVF or training without mirror feedback. The outcomes for the untrained hand were quantified by scores from five motor tasks. The results demonstrated that MVF and VT significantly increase the motor performance of the untrained hand by the use of AO. We found that MVF was the most effective approach to increase the performance of the target effector. On the contrary, the combination of MVF and VT turns out to be less effective looking from clinical perspective. The gathered results suggest that action-related motor competence with the untrained hand is acquired by both mirror-based and video-based AO.

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.