Revised Definition of Neuropathic Pain and Its Grading System: An Open Case Series Illustrating Its Use in Clinical Practice

The definition of neuropathic pain has recently been revised by an expert committee of the Neuropathic Pain Special Interest Group of the International Association for the Study of Pain (NeuPSIG) as "pain arising as direct consequence of a lesion or disease affecting the somatosensory system," and a grading system of "definite," "probable," and "possible" neuropathic pain has been introduced. This open case series of 5 outpatients (3 men, 2 women; mean age 48 +/- 12 years) demonstrates how the grading system can be applied, in combination with appropriate confirmatory testing, to diagnosis neuropathic conditions in clinical practice. The proposed grading system includes a dynamic algorithm …

S2.2 Assessment of neuropathic pain. I. Psychophysical methods

Detection of central circuits implicated in the formation of novel pain memories

Jaymin Upadhyay,1 Julia Granitzka,1 Thomas Bauermann,2 Ulf Baumgärtner,3 Markus Breimhorst,1 Rolf-Detlef Treede,3 Frank Birklein1 1Department of Neurology, 2Department of Neuroradiology, University Medical Centre, Johannes Gutenberg University Mainz, Mainz, 3Department of Neurophysiology, Center for Biomedicine and Medical Technology Mannheim (CBTM), Heidelberg University, Mannheim, Germany Abstract: Being able to remember physically and emotionally painful events in one’s own past may shape behavior, and can create an aversion to a variety of situations. Pain imagination is a related process that may include recall of past experiences, in addition to production of sensor…

Emotion Elicitation: A Comparison of Pictures and Films

Abstract Pictures and film clips are widely used and accepted stimuli to elicit emotions. Based on theoretical arguments it is often assumed that the emotional effects of films exceed those of pictures, but to date this assumption has not been investigated directly. The aim of the present study was to compare pictures and films in terms of their capacity to induce emotions verified by means of explicit measures. Stimuli were (a) single pictures presented for 6 s, (b) a set of three consecutive pictures with emotionally congruent contents presented for 2 s each, (c) short film clips with a duration of 6 s. A total of 144 participants rated their emotion and arousal states following stimulus …

Multiple Somatotopic Representations of Heat and Mechanical Pain in the Operculo-Insular Cortex: A High-Resolution fMRI Study

Whereas studies of somatotopic representation of touch have been useful to distinguish multiple somatosensory areas within primary (SI) and secondary (SII) somatosensory cortex regions, no such analysis exists for the representation of pain across nociceptive modalities. Here we investigated somatotopy in the operculo-insular cortex with noxious heat and pinprick stimuli in 11 healthy subjects using high-resolution (2 × 2 × 4 mm) 3T functional magnetic resonance imaging (fMRI). Heat stimuli (delivered using a laser) and pinprick stimuli (delivered using a punctate probe) were directed to the dorsum of the right hand and foot in a balanced design. Locations of the peak fMRI responses were c…

Laser guns and hot plates

204 PINPRICK-EVOKED POTENTIALS (PEPS): A NOVEL TOOL TO ASSESS CENTRAL SENSITISATION IN HUMANS

Asymmetry in the human primary somatosensory cortex and handedness.

Brain asymmetry is a phenomenon well known for handedness and language specialization and has also been studied in motor cortex. Less is known about hemispheric asymmetries in the somatosensory cortex. In the present study, we systematically investigated the representation of somatosensory function analyzing early subcortical and cortical somatosensory-evoked potentials (SEP) after electrical stimulation of the right and left median nerve. In 16 subjects, we compared thresholds, the peripheral neurogram at Erb point, and, using MRI-based EEG source analysis, the P14 brainstem component as well as N20 and P22, the earliest cortical responses from the primary sensorimotor cortex. Handedness w…

Clinical usefulness of laser-evoked potentials

In contrast to the function of the visual or auditory pathways which are electrophysiologically accessible by visual or auditory evoked potentials, the somatosensory pathway cannot be investigated as a whole by conventional somatosensory evoked potentials (SEP), because these only reflect function of large fibers, dorsal columns, medial lemniscus and their thalamo-cortical projections mediating sensations like touch and vibration. The other half of the somatosensory system, signaling temperature and pain perception, uses a different set of afferents and different central pathways, the function of which is accessible by laser-evoked potentials (LEPs). LEP can document lesions of the spinotha…

Explicit episodic memory for sensory-discriminative components of capsaicin-induced pain: Immediate and delayed ratings

Pain memory is thought to affect future pain sensitivity and thus contribute to clinical pain conditions. Systematic investigations of the human capacity to remember sensory features of experimental pain are sparse. In order to address long-term pain memory, nine healthy male volunteers received intrader- mal injections of three doses of capsaicin (0.05, 1 and 20 lg, separated by 15 min breaks), each given three times in a balanced design across three sessions at one week intervals. Pain rating was performed using a computerized visual analogue scale (0-100) digitized at 1/s, either immediately online or one hour or one day after injection. Subjects also recalled their pains one week later.…

34. The impact of partial sleep deprivation on the modulation of pain: Psychophysical and neurophysiological correlates

Dipole source analyses of laser evoked potentials obtained from subdural grid recordings from primary somatic sensory cortex

The cortical potentials evoked by cutaneous application of a laser stimulus (laser evoked potentials, LEP) often include potentials in the primary somatic sensory cortex (S1), which may be located within the subdivisions of S1 including Brodmann areas 3A, 3B, 1, and 2. The precise location of the LEP generator may clarify the pattern of activation of human S1 by painful stimuli. We now test the hypothesis that the generators of the LEP are located in human Brodmann area 1 or 3A within S1. Local field potential (LFP) source analysis of the LEP was obtained from subdural grids over sensorimotor cortex in two patients undergoing epilepsy surgery. The relationship of LEP dipoles was compared wi…

13 LASER-EVOKED POTENTIALS IN PERIPHERAL NEUROPATHY

Laser-evoked potentials for assessment of nociceptive pathways in humans

I n their Focus article, Chen, Arendt-Nielsen, and Plaghki [8] provide a comprehensive review of the . literature o~ human evoked potentials that ~re elicited by noxious heat, usually generated by Infrared laser stimulators. From this review, we identified four issues that may deserve a comment: (1) Standardize the experiment or its scientific report? (2) Nociception and pain. (3) What do laser-evoked potentials (LEPs) really measure? (4) Rational clinical use. For the sake of brevity, we do not attempt to quote all relevant literature; a complete literature survey can be found in a recent review paper by Bromm and Lorenz [4].

High opiate receptor binding potential in the human lateral pain system

To determine how opiate receptor distribution is co-localized with the distribution of nociceptive areas in the human brain, eleven male healthy volunteers underwent one PET scan with the subtype-nonselective opioidergic radioligand [(18)F]fluoroethyl-diprenorphine under resting conditions. The binding potential (BP), a parameter for the regional cerebral opioid receptor availability, was computed using the occipital cortex as reference region. The following regions of interest (ROIs) were defined on individual MR images: thalamus, sensory motor strip (SI/MI area), frontal operculum, parietal operculum, anterior insular cortex, posterior insular cortex, anterior cingulate cortex (ACC; peri-…

Inward currents in primary nociceptive neurons of the rat and pain sensations in humans elicited by infrared diode laser pulses

Radiant heat is often used to study nociception in vivo. We now used infrared radiation generated by a diode laser stimulator (wavelength 980 nm) to investigate transduction mechanisms for noxious heat stimuli in acutely dissociated dorsal root ganglion (DRG) neurons of rats in vitro. The laser stimulator offered the unique opportunity to test whether the same stimuli also elicit pain sensations in humans. A specific heat-induced current (I(heat)) was elicited in six of 13 small DRG neurons (diameteror =30 microm) tested in the whole-cell configuration of the patch-clamp mode. Current responses in the seven heat-insensitive neurons were within the range explainable by the temperature depend…

Abolished laser-evoked potentials and normal blink reflex in midlateral medullary infarction.

We investigated two patients presenting with the rare finding of almost isolated hemianalgesia with a sensory level on the contralateral side sparing the face. Clinical findings, electrophysiological studies (absent laser-evoked pain-related somatosensory potentials, normal electrically evoked somatosensory potentials, magnetically evoked potentials, and blink reflexes), and magnetic resonance imaging showed the ventrolateral medullar tegmentum containing the spinothalamic tract to be affected by lacunar infarction. The blink reflex R2 component was unimpaired in both patients.

Neurogenic hyperalgesia versus painful hypoalgesia: two distinct mechanisms of neuropathic pain

Patients with sensory disturbances of painful and non-painful character show distinct changes in touch and/or pain sensitivity. The patterns of sensory changes were compared to those of human surrogate models of neuropathic pain to assess the underlying mechanisms. We investigated 30 consecutive in-patients with dysaesthesia of various origins (peripheral, spinal, and brainstem lesions) and 15 healthy subjects. Tactile thresholds were determined with calibrated von Frey hairs (1.1mm). Thresholds and stimulus-response functions for pricking pain were determined with a series of calibrated punctate mechanical stimulators (0.2mm). Allodynia was tested by light stroking with a brush, Q-tip, and…

Combined EEG and MEG analysis of early somatosensory evoked activity in children and adolescents with focal epilepsies

Abstract Objective The study aimed to evaluate differences between EEG and MEG analysis of early somatosensory evoked activity in patients with focal epilepsies in localizing eloquent areas of the somatosensory cortex. Methods Twenty-five patients (12 male, 13 female; age 4–25 years, mean 11.7 years) were included. Syndromes were classified as symptomatic in 17, idiopathic in 2 and cryptogenic in 6 cases. 10 patients presented with malformations of cortical development (MCD). 122 channel MEG and simultaneous 33-channel EEG were recorded during tactile stimulation of the thumb (sampling rate 769 Hz, band-pass 0.3–260 Hz). Forty-four hemispheres were analyzed. Hemispheres were classified as t…

Differential nociceptive deficits in patients with borderline personality disorder and self-injurious behavior: laser-evoked potentials, spatial discrimination of noxious stimuli, and pain ratings.

Approximately 70-80% of women meeting criteria for borderline personality disorder (BPD) report attenuated pain perception or analgesia during non-suicidal, intentional self-mutilation. The aim of this study was to use laser-evoked potentials (LEPs) and psychophysical methods to differentiate the factors that may underlie this analgesic state. Ten unmedicated female patients with BPD (according to DSM-IV) and 14 healthy female control subjects were investigated using brief radiant heat pulses generated by a thulium laser and five-channel LEP recording. Heat pulses were applied as part of a spatial discrimination task (two levels of difficulty) and during a mental arithmetic task. BPD patien…

151. Structural and functional asymmetry in human parietal opercular cortex

Mechanisms and predictors of chronic facial pain in lateral medullary infarction

The purpose of this study was to identify clinical predictors and anatomical structures involved in patients with pain after dorsolateral medullary infarction. Eight out of 12 patients (67%) developed poststroke pain within 12 days to 24 months after infarction. The pain occurred in the ipsilateral face (6 patients) and/or the contralateral limbs and trunk (5 patients, 3 of whom also had facial pain). Ipsilateral facial pain was significantly correlated with lower medullary lesions, including those of the spinal trigeminal tract and/or nucleus, as documented by magnetic resonance imaging. The R2 blink reflex component was abnormal only in patients with facial pain. Likewise, pain and temper…

High opiate receptor binding potential in the human lateral pain system: A (FEDPN)PET study

Dipole Source Analyses of Early Median Nerve SEP Components Obtained From Subdural Grid Recordings

The median nerve N20 and P22 SEP components constitute the initial response of the primary somatosensory cortex to somatosensory stimulation of the upper extremity. Knowledge of the underlying generators is important both for basic understanding of the initial sequence of cortical activation and to identify landmarks for eloquent areas to spare in resection planning of cortex in epilepsy surgery. We now set out to localize the N20 and P22 using subdural grid recording with special emphasis on the question of the origin of P22: Brodmann area 4 versus area 1. Electroencephalographic dipole source analysis of the N20 and P22 responses obtained from subdural grids over the primary somatosensor…

Left-hemisphere dominance in early nociceptive processing in the human parasylvian cortex.

Pain perception comprises sensory and emotional dimensions. While the emotional experience is thought to be represented in the right hemisphere, we here report a left-hemisphere dominance for the early sensory component of pain perception using brain electrical source analysis of laser-evoked potentials. Ten right-handed subjects underwent several series of laser radiant heat stimuli to pairs of parallel lines on the dorsum of the left or right hand. Stimulus location and intensity were randomised independently. The sensory-discriminative aspects of pain were emphasised by asking the subjects to perform either a spatial or an intensity discrimination task and were contrasted with active dis…

Interoceptive and multimodal functions of the operculo-insular cortex: tactile, nociceptive and vestibular representations.

The operculo-insular cortex has been termed the 'homeostatic control center' or 'general magnitude estimator' of the human mind. In this study, somatosensory, nociceptive and caloric vestibular stimuli were applied to reveal, whether there are mainly common, or possibly specific regions activated by one modality alone and whether lateralization effects, time pattern differences or influences of the aversive nature of the stimuli could be observed. Activation of the dorsal posterior insula was caused by all stimuli alike thus terming this area multimodal. Early phases of the noxious heat and caloric vestibular stimulation led to responses in the anterior insula. Using conjunction analyses we…

Spatial resolution of fMRI in the human parasylvian cortex: Comparison of somatosensory and auditory activation

Abstract In spite of its outstanding spatial resolution, the biological resolution of functional MRI may be worse because it depends on the vascular architecture of the brain. Here, we compared the activation patterns of the secondary somatosensory and parietal ventral cortex (SII/PV) with that of the primary auditory cortex and adjacent areas (AI/AII). These two brain regions are located immediately adjacent to each other on opposite banks of the Sylvian fissure, and are anatomically and functionally distinct. In 12 healthy subjects, SII/PV was activated by pneumatic tactile stimuli applied to the index finger (0.5 cm 2 contact area, 4 bar pressure), and AI/AII by amplitude-modulated tones…

Evidence for early activation of primary motor cortex and SMA after electrical lower limb stimulation using EEG source reconstruction

Compared to median nerve somatosensory evoked potentials (SEP), less is known about activity evoked by nerve stimulation of the lower limb. To understand the mechanisms and the physiology of sensor- and motor control it is useful to investigate the sensorimotor functions as revealed by a standardized functional status. Therefore, we investigated SEPs of the lower limb in 6 healthy male volunteers. For each side, tibial and peroneal nerves were stimulated transcutaneously at the fossa poplitea. The tibial nerves were also stimulated further distally at the ankle joint. Source localization was applied to 64-EEG-channel data of the SEPs. In contrast to somatosensory areas, which are activated …

Chapter 15 Pain and itch in Wallenberg's syndrome: anatomical–functional correlations

Publisher Summary The Wallenberg syndrome or dorso-lateral medullary infarction is the most common vascular syndrome of the medulla oblongata. Its clinical features include an ipsilateral Horner's syndrome, an ipsilateral limb ataxia, and mostly an ipsilateral but sometimes also a contralateral or bilateral decrease of pain and temperature sensibility of the face. Patients with Wallenberg's syndrome and with morphological (lesion) or functional (ipsilateral sensory deficit and delayed late blink reflex responses) show evidence of damage to the trigeminal tract and nucleus with sparing of the nucleus caudalis would develop facial pain. The trigeminal trophic syndrome (TTS), a very rare compl…

Brain electrical source analysis of primary cortical components of the tibial nerve somatosensory evoked potential using regional sources.

Tibial nerve somatosensory evoked potentials (SEPs) show higher amplitudes ipsilateral to the side of stimulation, whereas subdural recordings revealed a source in the foot area of the contralateral hemisphere. We now investigated this paradoxical lateralization by performing a brain electrical source analysis in the P40 time window (34-46 ms). The tibial nerve was stimulated behind the ankle (8 subjects). On each side, 2048 stimuli were applied twice. SEPs were recorded using 32 magnetic resonance imaging (MRI)-verified electrode positions (bandpass 0.5-500 Hz). In each case, the P40 amplitude was higher ipsilaterally (0.45 +/- 0.14 microV) than contralaterally (-0.49 +/- 0.16 microV). The…

Sensitivity of laser-evoked potentials versus somatosensory evoked potentials in patients with multiple sclerosis

Somatosensory evoked potentials (SEPs) play a less important role in the diagnosis of multiple sclerosis (MS) than visually evoked potentials. Since standard SEPs only reflect the dorsal column function, we now investigated spinothalamic tract function in patients with MS using laser-evoked potentials (LEPs).LEPs to thulium laser stimuli (3ms, 540 mJ, 5mm diameter) were recorded from 3 midline positions (Fz, Cz, Pz) in 20 patients with MS, and 6 patients with possible but unconfirmed MS. Peak latencies and peak-to-peak amplitude of the vertex potential negativity (N2) and positivity (P2) were evaluated and compared with normative values from 22 healthy control subjects. Median and tibial ne…