Sympathetic blockade increases tactile sensitivity

To determine whether tactile sensitivity of the normal skin is altered by suppression of sympathetic efferent activity, the effect of stellate ganglion block and epidural sympathetic block on touch threshold was studied. The study was performed on ten individuals with various chronic pain syndromes. Tactile sensitivity was measured in the normal skin area with the use of von Frey filaments and a two-alternative forced-choice procedure with a staircase presentation of touch stimuli. With stellate ganglion block, touch threshold decreased on the side of the block by 48.8 +/- 8.% (P = 0.002) without any significant change in the threshold on the healthy, nonblocked side (P = 0.003 for the difference between the sides). With epidural sympathetic block, touch threshold decreased to the same extent on the diseased and healthy sides, which were both affected by the block (46.2 +/- 11.4%, P = 0.027 and 47.7 +/- 12.5%, P = 0.032, respectively). The results show that sympathetic blockade increases tactile sensitivity. They also suggest that sympathetic efferent activity modulates the function of tactile receptors. It is hypothesized that the sympathetic modulation makes tactile receptors less sensitive to touch, less specific, and probably more prone to code tactile stimuli in such a way that the brain recognizes this code as pain.     

Touch to see: neuropsychological evidence of a sensory mirror system for touch

The observation of touch can be grounded in the activation of brain areas underpinning direct tactile experience, namely the somatosensory cortices. What is the behavioral impact of such a mirror sensory activity on visual perception? To address this issue, we investigated the causal interplay between observed and felt touch in right brain-damaged patients, as a function of their underlying damaged visual and/or tactile modalities. Patients and healthy controls underwent a detection task, comprising visual stimuli depicting touches or without a tactile component. Touch and No-touch stimuli were presented in egocentric or allocentric perspectives. Seeing touches, regardless of the viewing perspective, differently affects visual perception depending on which sensory modality is damaged: In patients with a selective visual deficit, but without any tactile defect, the sight of touch improves the visual impairment; this effect is associated with a lesion to the supramarginal gyrus. In patients with a tactile deficit, but intact visual perception, the sight of touch disrupts visual processing, inducing a visual extinction-like phenomenon. This disruptive effect is associated with the damage of the postcentral gyrus. Hence, a damage to the somatosensory system can lead to a dysfunctional visual processing, and an intact somatosensory processing can aid visual perception.     

Representations of pleasant and painful touch in the human orbitofrontal and cingulate cortices

The cortical areas that represent affectively positive and negative aspects of touch were investigated using functional magnetic resonance imaging (fMRI) by comparing activations produced by pleasant touch, painful touch produced by a stylus, and neutral touch, to the left hand. It was found that regions of the orbitofrontal cortex were activated more by pleasant touch and by painful stimuli than by neutral touch and that different areas of the orbitofrontal cortex were activated by the pleasant and painful touches. The orbitofrontal cortex activation was related to the affective aspects of the touch, in that the somatosensory cortex (SI) was less activated by the pleasant and painful stimuli than by the neutral stimuli. This dissociation was highly significant for both the pleasant touch (P < 0.006) and for the painful stimulus (P < 0.02). Further, it was found that a rostral part of the anterior cingulate cortex was activated by the pleasant stimulus and that a more posterior and dorsal part was activated by the painful stimulus. Regions of the somatosensory cortex, including SI and part of SII in the mid-insula, were activated more by the neutral touch than by the pleasant and painful stimuli. Part of the posterior insula was activated only in the pain condition and different parts of the brainstem, including the central grey, were activated in the pain, pleasant and neutral touch conditions. The results provide evidence that different areas of the human orbitofrontal cortex are involved in representing both pleasant touch and pain, and that dissociable parts of the cingulate cortex are involved in representing pleasant touch and pain.     

Pain measurement

Increasing evidence from laboratory methods in humans and animals indicates that pain arises from, and is modulated by, a number of mechanisms. In addition, these mechanisms are not static but change as pain persists. Recent human studies have demonstrated new aspects of pain processing at all levels of the central nervous system. Studies of the influence of analgesic agents on a large number of experimental pain measures have shown a preferential effect of opioids for attenuating the central integration of prolonged stimuli while local anesthetics may be more effective for brief stimulation. Studies of NK1 antagonists in man have shown results similar to those found with animals. There is little effect on brief stimulation of A delta and C-fiber nociceptors, including conditions that can evoke central summation. However, these antagonists, which block the effects of substance P, are effective in more persistent states such as postsurgical pain. Persistent pain can also alter the function of the large diameter A beta touch afferents, ranging from increased tactile sensitivity in inflammatory conditions to frank allodynia following nerve injury or focal nociceptor stimulation. Recent advances in evaluation of supraspinal pain processing in humans have demonstrated pain-related activation using both methods that assess synchronized neural activity and methods that infer this activity in the whole brain by local changes in regional cerebral blood flow. These methods have begun to identify brain regions associated with the multiple dimensions and processing of painful stimulation and the modulation of these processes by pharmacological agents and non-pharmacological interventions.     

Concentration-effect relationship of intravenous lidocaine on the allodynia of complex regional pain syndrome types I and II

BACKGROUND: Several lines of evidence suggest that neuropathic pain (including Complex Regional Pain Syndrome [CRPS] I and CRPS II) is mediated in part by an increase in the density of voltage-sensitive sodium channels in injured axons and the dorsal root ganglion of injured axons. This study sought to characterize the effects of intravenous lidocaine (a sodium channel blocker) on acute sensory thresholds within the painful area and the size of the painful area in patients suffering from CRPS I and II. METHODS: This study used a randomized, double-blind, placebo-controlled design in 16 subjects suffering from CRPS I and II with a prominent allodynia. Each subject received an intravenous infusion of lidocaine and diphenhydramine separated by 1 week. A computer-controlled infusion pump targeted stair-step increases in plasma levels of lidocaine of 1, 2, and 3 microg/ml. At baseline and at each plasma level, spontaneous and evoked pain scores and neurosensory testing within the painful area were measured. The neurosensory testing consisted of thermal thresholds, tactile thresholds and the area of allodynia to punctate, and stroking and thermal stimuli. RESULTS: Intravenous lidocaine and diphenhydramine had no significant effect on the cool, warm, or cold pain thresholds. However, lidocaine caused a significant elevation of the hot pain thresholds in the painful area. Intravenous lidocaine caused a significantly decreased response to stroking and cool stimuli in the allodynic area. There was also a significant decrease in pain scores to cool stimuli at all plasma levels and the spontaneous pain at the highest plasma level. CONCLUSIONS: This study demonstrates that intravenous lidocaine affects pain in response to cool stimuli more than mechanical pain in subjects with neuropathic pain. There is a lesser effect on spontaneous pain and pain induced by stroking stimuli and no effect on the pain induced by punctate stimuli.     

Mechanical noxious stimuli cause bilateral activation of parietal operculum in callosotomized subjects

The patterns of cortical activation evoked by tactile and mechanical painful stimulation in six normal subjects and three patients with complete resection of the corpus callosum are described and compared, with emphasis on the parietal operculum. Stimulus-related cortical activation was investigated by functional magnetic resonance imaging. In both groups, painful stimulation activated the first somatosensory, insular and cingulate cortices in the contralateral hemisphere, and the parietal opercular cortex in both hemispheres. Comparison between the two patterns of cortical activation demonstrated that ipsilateral activation by unilateral painful stimulation is at least partially independent of the corpus callosum and suggests a different organization of the pain and touch systems.     

Concentration-Effect Relationship of Intravenous Lidocaine on the Allodynia of Complex Regional Pain Syndrome Types I and II

Background: Several lines of evidence suggest that neuropathic pain (including Complex Regional Pain Syndrome [CRPS] I and CRPS II) is mediated in part by an increase in the density of voltage-sensitive sodium channels in injured axons and the dorsal root ganglion of injured axons. This study sought to characterize the effects of intravenous lidocaine (a sodium channel blocker) on acute sensory thresholds within the painful area and the size of the painful area in patients suffering from CRPS I and II.

Methods: This study used a randomized, double-blind, placebo-controlled design in 16 subjects suffering from CRPS I and II with a prominent allodynia. Each subject received an intravenous infusion of lidocaine and diphenhydramine separated by 1 week. A computer-controlled infusion pump targeted stair-step increases in plasma levels of lidocaine of 1, 2, and 3 [mu]g/ml. At baseline and at each plasma level, spontaneous and evoked pain scores and neurosensory testing within the painful area were measured. The neurosensory testing consisted of thermal thresholds, tactile thresholds and the area of allodynia to punctate, and stroking and thermal stimuli.

Results: Intravenous lidocaine and diphenhydramine had no significant effect on the cool, warm, or cold pain thresholds. However, lidocaine caused a significant elevation of the hot pain thresholds in the painful area. Intravenous lidocaine caused a significantly decreased response to stroking and cool stimuli in the allodynic area. There was also a significant decrease in pain scores to cool stimuli at all plasma levels and the spontaneous pain at the highest plasma level.     

Anaesthesia of the axillary plexus induces rapid improvement of sensory function in the contralateral hand: an effect of interhemispheric plasticity.

Acute improvement of sensory functions in the contralateral hand during experimental, tourniquet-induced anaesthesia has been described. Tourniquet compression over an extended time period, however, may be painful - which may influence the result. To study the effects of deafferentation of the upper extremity with the pain factor eliminated, we investigated 100 patients with anaesthetised axillary plexus for perception of touch and tactile discrimination in the contralateral (unanaesthetised) hand. Anaesthesia induced a rapid, significant, improvement in tactile discrimination in the contralateral hand, compared with before anaesthesia, measured as two-point discrimination (p=0.0001), and perception of touch, measured with Semmes-Weinstein monofilament (p=0.0005). The improvement lasted as long as the arm was anaesthetised. Understanding the mechanisms of brain plasticity, including interhemispheric plasticity, is essential for designing appropriate strategies for upregulation and downregulation of cortical reorganisational changes to promote sensory relearning after nerve injury.     

Human tactile perception as a standard for artificial tactile sensing--a review

In this paper, we examine the most important features of human skin tactile properties with special emphasis on the characteristics which are vital in the design of artificial systems. Contrary to the visual and auditory senses, the touch signal is not a well-defined quantity. As a result, the researchers of this field are still dealing with the basics of collecting the most relevant data. Following this, mimicking the sense of touch by producing artificial tactile skin is a challenging process. Although the sense of touch is widely distributed all over the human body, the tactile perception in the human hand is of great importance in terms of surgical and medical robotics applications. In this study, the role of various mechanoreceptors in the human hand, such as, RA, SA I, SA II, and PC units are discussed in relation to the stimuli like force, position, softness, and surface texture. Taking human hand as a suitable tactile model, the necessary engineering features of an artificial tactile sensor, such as, spatial and temporal resolutions, force sensitivity, and linearity, are being reviewed. In this work, we also report on the current and possible future applications of tactile sensors in various surgical procedures.     

Anaesthesia of the axillary plexus induces rapid improvement of sensory function in the contralateral hand: An effect of interhemispheric plasticity

Acute improvement of sensory functions in the contralateral hand during experimental, tourniquet-induced anaesthesia has been described. Tourniquet compression over an extended time period, however, may be painful – which may influence the result. To study the effects of deafferentation of the upper extremity with the pain factor eliminated, we investigated 100 patients with anaesthetised axillary plexus for perception of touch and tactile discrimination in the contralateral (unanaesthetised) hand. Anaesthesia induced a rapid, significant, improvement in tactile discrimination in the contralateral hand, compared with before anaesthesia, measured as two-point discrimination (p=0.0001), and perception of touch, measured with Semmes-Weinstein monofilament (p=0.0005). The improvement lasted as long as the arm was anaesthetised. Understanding the mechanisms of brain plasticity, including interhemispheric plasticity, is essential for designing appropriate strategies for upregulation and downregulation of cortical reorganisational changes to promote sensory relearning after nerve injury.     

Responsiveness to stimuli of bispectral index,middle latency auditory evoked potentials and clinical scales in critically ill children

We performed simultaneous recordings of Bispectral Index (BIS) and middle latency auditory evoked potentials. We also recorded two clinical scales, the Modified Ramsay scale and the COMFORT scale. Heart rate and blood pressure were measured once a day, for a maximum of 5 days, in 81 critically ill children. Changes with tactile, auditory, and painful stimuli were analysed. All the stimuli significantly increased the BIS value, the painful stimulus having the greatest effect. The painful stimulus was the only one that altered the middle latency auditory evoked potentials. Although the responses of the clinical scales to stimuli were statistically significant, they were of little clinical relevance. None of the stimuli used significantly altered the heart rate or blood pressure. We conclude that tactile, auditory and painful stimuli produced changes of little relevance in the clinical scales, BIS or middle latency auditory evoked potentials. We found the BIS was the most sensitive method and the painful stimulus had the greatest effect.     

Peripheral nerve injury sensitizes the response to visceral distension but not its inhibition by the antidepressant milnacipran

BACKGROUND: Manipulations that cause hypersensitivity to visceral stimuli have been shown to also result in hypersensitivity to somatic stimuli coming from convergent dermatomes, but the converse has not been examined. The authors tested whether lumbar spinal nerve ligation in rats, a common model of neuropathic pain that results in hypersensitivity to somatic stimuli, also leads to hypersensitivity to visceral stimuli coming from convergent dermatomes and whether pharmacology of inhibition differed between these two sensory modalities. METHODS: Female Sprague-Dawley rats were anesthetized, and the left L5 and L6 spinal nerves were ligated. Animals received either intrathecal saline or milnacipran (0.1-3 microg), and withdrawal thresholds to mechanical testing in the left hind paw, using von Frey filaments, and visceral testing, using balloon colorectal distension, were determined. RESULTS: Nerve ligation resulted in decreases in threshold to withdrawal to somatic mechanical stimulation (from 13 +/- 1.8 g to 2.7 +/- 0.7 g) and also in decreases in threshold to reflex response to visceral stimulation (from 60 mmHg to 40 mmHg). Intrathecal milnacipran increased withdrawal threshold to somatic stimulation in a dose-dependent manner but failed to alter the response to noxious visceral stimulation. CONCLUSIONS: Injury of nerves innervating somatic structures enhances nociception from stimulation of viscera with convergent input from nearby dermatomes, suggesting that somatic neuropathic pain could be accompanied by an increased likelihood of visceral pain. Lack of efficacy of the antidepressant milnacipran against visceral stimuli suggests that visceral hypersensitivity may not share the same pharmacology of inhibition as somatic hypersensitivity after nerve injury.     

Directing attention to locations and to sensory modalities: multiple levels of selective processing revealed with PET

We used positron emission tomography (PET) to investigate the neural correlates of selective attention in humans. We examined the effects of attending to one side of space versus another (spatial selection) and to one sensory modality versus another (intermodal selection) during bilateral, bimodal stimulation of vision and touch. Attention toward one side resulted in greater activity in several contralateral areas. In somatosensory cortex, these spatial attentional modulations were found only when touch was relevant. In the intraparietal sulcus, spatial attentional effects were multimodal, independent of the modality attended. In occipital areas, spatial modulations were also found during both visual and tactile attention, indicating that tactile attention can affect activity in visual cortex; but occipital areas also showed more activity overall during visual attention. This suggests that while spatial attention can exert multimodal influences on visual areas, these still maintain their specificity for the visual modality. Additionally, irrespective of the attended side, attending to vision activated posterior parietal and superior premotor cortices, while attending to touch activated the parietal operculi. We conclude that attentional selection operates at multiple levels, with attention to locations and attention to modalities showing distinct effects. These jointly contribute to boost processing of stimuli at the attended location in the relevant modality.     

Andauernder idiopathischer Gesichtsschmerz (AIGS) und Mundschleimhautbrennen

Acute pain may be triggered by mechanical, thermal or chemical stimuli on free ends of afferent nociceptive nerve fibers, the nociceptors. Acute pain achieves a warning and protecting function against real or potential tissue damaging. Pain is not the result of passive conduction of afferent noxious stimuli but the outcome of the cerebral capability to integrate interacting psychological and physiological processes. Severe acute painful stimuli or long-lasting chronic noxious stimuli may induce peripheral and central sensibilization of neural nociceptive systems and may be responsible for the initiation of chronic, self-maintained neuropathic pain. Chronic pain loses its evolutionary function and becomes a severe and stressing painful disorder. The causes and pathogenesis of idiopathic facial pain and burning mouth syndrome are not well-known to date, but multiple central neuropathic and psychogenic interacting conditions are important factors. In view of the fundamental biological differences between acute pain and chronic pain disorders, detailed knowledge of clinical symptomatology and pathogenic context will be helpful to evade monocausal oriented, futile methods of treatment.     

Somatotopy in human primary somatosensory cortex in pain system

BACKGROUND: Compared with somatotopical organization (somatotopy) in the postcentral gyrus in the tactile system, somatotopy in the pain system is not well understood. The aim of this study is to elucidate whether there is somatotopy in the human pain system. METHODS: To elucidate the somatotopy of nociceptive neurons in the postcentral gyrus, the authors recorded pain-evoked cortical responses to noxious intraepidermal electrical stimulation applied to the left hand and left foot in 11 male subjects, using magnetoencephalography. RESULTS: Brief painful stimuli evoked sustained cortical activity in the primary somatosensory cortex (SI) in the hemisphere contralateral to the stimulated side and in the secondary somatosensory cortex in both hemispheres. In SI, representations of the hand and foot were distinctly separated, with a more medial and posterior location for the foot, whereas no significant difference was found in the locations for the secondary somatosensory cortex dipole. The SI arrangement along the central sulcus was compatible with the homunculus revealed by Penfield using direct cortical stimulation during surgery. CONCLUSIONS: The human pain system contains a somatotopical representation in SI but with less somatotopical organization in the secondary somatosensory cortex. The current results provide supporting evidence of SI involvement in human pain perception and suggest that human SI subserves the localization of the stimulated site in nociceptive processing.     

Somatotopy in Human Primary Somatosensory Cortex in Pain System

Background: Compared with somatotopical organization (somatotopy) in the postcentral gyrus in the tactile system, somatotopy in the pain system is not well understood. The aim of this study is to elucidate whether there is somatotopy in the human pain system.

Methods: To elucidate the somatotopy of nociceptive neurons in the postcentral gyrus, the authors recorded pain-evoked cortical responses to noxious intraepidermal electrical stimulation applied to the left hand and left foot in 11 male subjects, using magnetoencephalography.

Results: Brief painful stimuli evoked sustained cortical activity in the primary somatosensory cortex (SI) in the hemisphere contralateral to the stimulated side and in the secondary somatosensory cortex in both hemispheres. In SI, representations of the hand and foot were distinctly separated, with a more medial and posterior location for the foot, whereas no significant difference was found in the locations for the secondary somatosensory cortex dipole. The SI arrangement along the central sulcus was compatible with the homunculus revealed by Penfield using direct cortical stimulation during surgery.     

Effects of gabapentin on experimental somatic pain and temporal summation

BACKGROUND AND OBJECTIVES: Gabapentin is used for treatment of neuropathic pain, but its effect on different somatic pain modalities and integrative mechanisms are not completely understood. The aim of this double-blind, placebo-controlled experimental pain study, conducted on 20 healthy volunteers, was to examine the effect of a single dose of 1200 mg gabapentin on multi-modal experimental cutaneous and muscle pain models. METHODS: The following pain models were applied: (1) pain thresholds to single and repeated cutaneous and intramuscular electrical stimulation (temporal summation to 5 stimuli delivered at 2 Hz); (2) stimulus-response function relating pain intensity scores (visual analog scale, VAS) to increasing current intensities for electrical skin and muscle stimuli (single and repeated, determined at baseline); and (3) the pain intensity (VAS) and pain areas after intramuscular injection of hypertonic saline. Pain assessments were performed prior to, and at 4, 6, and 8 hours after medication. RESULTS: When responses were averaged across the post-dose times, gabapentin: (1) significantly increased the temporal summation pain threshold in skin compared with placebo (P = .03); (2) significantly reduced the area under the pain intensity curve to hypertonic saline injections in the muscle (P = .02); and (3) significantly reduced the area of pain evoked by hypertonic saline (P = .03). CONCLUSIONS: Gabapentin reduces temporal summation of skin stimuli at pain threshold intensities; this may have potential as a biomarker for drugs with efficacy on neurogenic pain. The data also suggest that tonic muscle pain is responsive to gabapentin treatment and suggest further clinical studies.     

Effect of systemic N-methyl-D-aspartate receptor antagonist (ketamine) on primary and secondary hyperalgesia in humans

Ketamine reduces nociception by binding noncompetitively to the N- methyl-D-aspartate (NMDA) receptor, activation of which increases spinal hypersensitivity. We studied 19 healthy, unmedicated male volunteers, aged 20-31 yr. Burn injuries were produced on the medial surface of the dominant calf with a 25 x 50 mm rectangular thermode. On 3 separate days, at least 1 week apart, subjects received a bolus of either ketamine 0.15 mg kg-1, ketamine 0.30 mg kg-1 or placebo, delivered by a mechanical infusion pump over 15 min. The bolus was followed by continuous infusion of ketamine 0.15 mg kg-1 h-1, ketamine 0.30 mg kg-1 h-1 or placebo, respectively, for 135 min. Ketamine reduced the magnitude of both primary and secondary hyperalgesia, and also pain evoked by prolonged noxious heat stimulation, in a dose- dependent manner. In contrast, ketamine did not alter phasic heat pain perception (perception of transient, painful, thermal stimuli) in undamaged skin. The analgesic effects of ketamine in the burn injury model are in agreement with results from experimental studies, and can be distinguished from those of local anaesthetics and opioids. Side effects caused by continuous infusion of ketamine 0.15 and 0.30 mg kg-1 h-1 were frequent but clinically acceptable.      

Low-dose Lidocaine Suppresses Experimentally Induced Hyperalgesia in Humans

Background: The antinociceptive effects of systemically administered local anesthetics have been shown in various conditions, such as neuralgia, polyneuropathy, fibromyalgia, and postoperative pain. The objective of the study was to identify the peripheral mechanisms of action of low-dose local anesthetics in a model of experimental pain.

Methods: In a first experimental trial, participants (n = 12) received lidocaine systemically (a bolus injection of 2 mg/kg in 10 min followed by an intravenous infusion of 2 mg [middle dot]-1 [middle dot] h-1 for another 50 min). In a second trial, modified intravenous regional anesthesia was administered to exclude possible central analgesic effects. In one arm, patients received an infusion of 40 ml lidocaine, 0.05%; in their other arm, 40 ml NaCl, 0.9%, served as a control. In both trials, calibrated tonic and phasic mechanical and chemical (histamine) stimuli were applied to determine differentially the impairment of tactile and nociceptive perception.

Results: Mechanical sensitivity to touch, phasic mechanical stimuli of noxious intensity, and heat pain thresholds remained unchanged after systemic and regional application of the anesthetic. In contrast, histamine-induced itch (intravenous regional anesthesia), axon reflex flare (systemic treatment), and development of acute mechanical hyperalgesia during tonic pressure (12 N; 2 min) of an interdigital web was significantly suppressed after both treatments.     

Imaging pain modulation by subanesthetic S-(+)-ketamine

Little is known about the effects of low-dose S-(+)-ketamine on the cerebral processing of pain. We investigated the effects of subanesthetic IV S-(+)-ketamine doses on the perception of experimental painful heat stimuli. Healthy volunteers were evaluated with functional magnetic resonance imaging (fMRI) while receiving the painful stimuli in conjunction with placebo and increasing doses (0.05, 0.1, 0.15 mg x kg(-1) x h(-1)) of ketamine infusion. Vital variables were monitored and all subjects rated pain intensity and unpleasantness on a numerical rating scale. Alterations in consciousness were measured using a psycho-behavioral questionnaire. Pain unpleasantness declined as ketamine dosage was increased (55.1% decrease, placebo versus 0.15 mg x kg(-1) x h(-1) ketamine). Pain intensity ratings also decreased with increasing ketamine dosage but to a lesser extent (23.1% decrease). During placebo administration, a typical pain activation network (thalamus, insula, cingulate, and prefrontal cortex) was found, whereas decreased pain perception with ketamine was associated with a dose-dependent reduction of pain-induced cerebral activations. Analysis of the dose-dependent ketamine effects on pain processing showed a decreasing activation of the secondary somatosensory cortex (S2), insula and anterior cingulate cortex. This part of the anterior cingulate cortex (midcingulate cortex) has been linked with the affective pain component that underlines the potency of ketamine in modulating affective pain processing.