Remote activation of referred phantom sensation and cortical reorganization in human upper extremity amputees

Phantom limb sensation, whether painful or not, frequently occurs after peripheral nerve lesions. It can be elicited by stimulating body parts adjacent to the amputation site (referred to as phantom sensation) and it is often similar in quality to the stimulation at the remote site. The present study induced referred phantom sensations in two upper limb amputees. Neuroelectric source imaging (ESI) as well as functional magnetic resonance imaging (fMRI) was used to assess reorganization in primary somatosensory cortex (SI). Whereas recent studies found mislocalization of sensation related to stimulation mainly in regions adjacent and ipsilateral to the amputation site, we report here the elicitation of phantom sensation in the arm by stimulation in the lower body part both ipsi- and contralateral to the amputation in two arm amputees. The fMRI evaluation of one patient showed no shift in the location of the foot whereas ESI revealed major reorganization of the mouth region in primary somatosensory cortex in both patients. These data suggest that cortical structures other than SI might be contributing to the phenomenon of referred sensation. Candidate structures are the thalamus, secondary somatosensory cortex, posterior parietal cortex and prefrontal cortex.     

Painful and non-painful pressure sensations from human skeletal muscle

Painful and non-painful pressure sensations from muscle are generally accepted to exist but the peripheral neural correlate has not been clarified. The aim of the present human study was to assess the non-painful and painful pressure sensitivity with (1) anaesthetised skin, and (2) anaesthetised skin combined with a block of large diameter muscle afferents. The skin was anaesthetised by a topically applied anaesthetic cream and later lidocaine was administrated subcutaneously. The pressure sensitivity was assessed quantitatively by computer-controlled pressure stimulation on the anterior tibial muscle. Thresholds to detection, pain and pain tolerance were assessed. In the first experiment, computer-controlled needle insertion depths evoking touch and pain sensations were used to assess the efficacy of cutaneous anaesthesia. Touch and pain sensations evoked during needle insertions were found to be superficial in intact skin but when anaesthetised, touch sensation was occasionally evoked at depths related to penetration of the fascia. With the skin completely anaesthetised to brush and von Frey hair pinprick stimulation, skin indentation with the strongest von Frey hair caused a sensation described as a deep touch sensation. Simultaneously, pressure detection and pain thresholds increased but it was still possible to elicit non-painful and painful pressure sensation in all subjects. In a second experiment, a differential nerve block of group I and II afferent fibres was obtained by full-leg ischaemia simultaneously with cutaneous anaesthesia. The efficacy of the tourniquet block was continuously assessed by a battery of somatosensory tests (heat, brush, vibration, electrical and movement detection) applied at the foot simultaneously with pressure stimulation on the anterior tibial muscle. After 20 min of ischaemia, group II afferent fibres mediating the sensations of movement detection, vibration and brush on the foot was blocked but the heat pain threshold was not affected. In this condition (anaesthetised skin and block of group I and II fibres from deep tissue) a pressure sensation was evoked in 70% of subjects although the pressure detection threshold was increased. The pressure pain sensitivity was decreased, which, however, might indicate a partial block of group III and IV muscle afferents. In a third experiment, the tactile sensations elicited by electrical stimulation of the tibialis anterior muscle and skin at the lower leg were significantly decreased after 20 min of ischaemia, validating the blocking effects of group I and II nerve fibres. The present data show a marginal contribution of cutaneous afferents to the pressure pain sensation that, however, is relatively more dependent on contributions from deep tissue group III and IV afferents. Moreover, a pressure sensation can be elicited from deep tissue probably mediated by group III and IV afferents involving low-threshold mechanoreceptors.     

Pain catastrophizing and cortical responses in amputees with varying levels of phantom limb pain: a high-density EEG brain-mapping study

Pain catastrophizing has been associated with phantom limb pain, but so far the cortical processes and the brain regions involved in this relationship have not been investigated. It was therefore tested whether catastrophizing was related to (1) spontaneous pain, (2) somatosensory activity and (3) cortical responses in phantom limb pain patients. The cortical responses were investigated via electroencephalography (EEG) as it has a high temporal resolution which may be ideal for investigating especially the attentional and hypervigilance aspect of catastrophizing to standardized acute stimuli. Eighteen upper limb amputees completed the pain catastrophizing scale. Patients’ spontaneous pain levels (worst and average pain, numerical rating scales) and thresholds to electrical stimulation (sensory detection and VRS2: intense but not painful) were determined. Non-painful electrical stimuli were applied to both the affected and non-affected arm, while high-resolution (128 channels) EEG signals were recorded. Catastrophizing accounted for significant amounts of the variance in relation to spontaneous pain, especially worst pain (64.1%), and it was significantly associated with thresholds. At the affected side, catastrophizing was significantly related to the power RMS of the N/P135 dipole located in the area around the secondary somatosensory cortex which has been shown to be associated with arousal and expectations. These findings corroborate the attentional model of pain catastrophizing by indicating that even non-painful stimuli are related to enhanced attention to and negative expectations of stimuli, and they suggest that memory processes may be central to understanding the link between catastrophizing and pain.     

Differentiation of visceral and cutaneous pain in the human brain

The widespread convergence of information from visceral, cutaneous, and muscle tissues onto CNS neurons invites the question of how to identify pain as being from the viscera. Despite referral of visceral pain to cutaneous areas, individuals regularly distinguish cutaneous and visceral pain and commonly have contrasting behavioral reactions to each. Our study addresses this dilemma by directly comparing human neural processing of intensity-equated visceral and cutaneous pain. Seven subjects underwent fMRI scanning during visceral and cutaneous pain produced by balloon distention of the distal esophagus and contact heat on the midline chest. Stimulus intensities producing nonpainful and painful sensations, interleaved with rest periods, were presented in each functional run. Analyses compared painful to nonpainful conditions. A similar neural network, including secondary somatosensory and parietal cortices, thalamus, basal ganglia, and cerebellum, was activated by visceral and cutaneous painful stimuli. However, cutaneous pain evoked higher activation bilaterally in the anterior insular cortex. Further, cutaneous but not esophageal pain activated ventrolateral prefrontal cortex, despite higher affective scores for visceral pain. Visceral but not cutaneous pain activated bilateral inferior primary somatosensory cortex, bilateral primary motor cortex, and a more anterior locus within anterior cingulate cortex. Our results reveal a common cortical network subserving cutaneous and visceral pain that could underlie similarities in the pain experience. However, we also observed differential activation patterns within insular, primary somatosensory, motor, and prefrontal cortices that may account for the ability to distinguish visceral and cutaneous pain as well as the differential emotional, autonomic and motor responses associated with these different sensations.     

EEG responses to tonic heat pain

The aim of the present study was to characterize the EEG response pattern specific for tonic pain which is an experimental pain model resembling clinical pain more closely than phasic pain. Tonic experimental pain was produced by a series of heat pulses 1°C above pain threshold over 10 min. A series of heat pulses 0.3°C below pain threshold and a constant temperature of 37°C served as non-painful heat control and as baseline condition, respectively. The level of attention was experimentally manipulated by instruction and by a distraction task. Twenty male, pain-free subjects had to rate the sensation intensity and sensation unpleasantness during thermal stimulation. Furthermore, a German version of the McGill Pain Questionnaire was to be filled out after tonic painful heat stimulation. The EEG was recorded via 10 leads according to 10/20 convention. Power density was calculated for the usual frequency bands. The ratings showed that tonic painful heat was experienced clearly distinct from tonic non-painful heat. An EEG response pattern emerged characterized by a rather generalized increased delta² activity, a left-biased fronto-temporally diminished theta activity, a fronto-temporal decrease in the alpha¹ activity and a left-sided temporal increase in the beta¹ activity. This observation agrees well with the findings of others. However, there was no evidence in our data that these EEG changes are specific to tonic heat pain as opposed to changes observed during tonic non-painful heat stimulation. Accordingly, the repeatedly reported EEG patterns are also likely to be produced by other forms of strong somatosensory stimuli and to be not specific for pain.     

Neural correlates of prickle sensation: a percept-related fMRI study

The painful sensations produced by a laceration, freeze, burn, muscle strain or internal injury are readily distinguishable because each is characterized by a particular sensory quality such as sharp, aching, burning or prickling. We propose that there are specific neural correlates of each pain quality, and here we used a new functional magnetic resonance imaging (fMRI) method to identify time-locked responses to prickle sensations that were evoked by noxious cold stimuli. With percept-related fMRI, we identified prickle-related brain activations in the anterior cingulate cortex (ACC), insula, secondary somatosensory cortex (S2), prefrontal cortex (PFC), premotor cortex (PMC), caudate nucleus and dorsomedial thalamus, indicating that multiple pain, sensory and motor areas act together to produce the prickle sensation.     

Different EEG topographic effects of painful and non-painful intramuscular stimulation in man

To clarify the specific effects of muscle pain on electroencephalogram (EEG) activation in man, painful and non-painful sensations were produced by intramuscular injections of capsaicin and vehicle solution in the left brachioradialis muscle, with identical procedures in 15 male volunteers. Thirty-one channel EEG data acquired before, during and after the two injections were analysed and compared in respect of topography and power spectrum. Although the painful and non-painful muscular stimulations evoked similar EEG topographic patterns, statistics demonstrated that distinct EEG activation over different areas of the head were induced by the painful and non-painful stimulation compared with the baselines. The decreases in theta and alpha-1 (8-10.5 Hz) activity in central and posterior parietal parts were evoked by non-painful stimulation, but the decreases in alpha-1 and alpha-2 (11-13.5 Hz) activities in the posterior part of the head were induced by painful stimulation. The alpha-2 activity augmented during the waning pain following a decrease in the overt pain. Comparing the EEG changes between baseline, non-painful and painful stimulations as well as waning pain, we found that the increase in beta-2 activity during muscle pain was significant over the extensive areas of the head, whereas a significant increase in alpha-2 activity took place at the posterior part of the head during waning pain following a marked decrease in overt pain. These results may imply that the painful and non-painful muscular stimulations evoke distinct EEG activation in different neural networks of the human brain and the intensity of nociceptive input from muscle may encode the variety of topographic EEG changes.     

Painful muscle stimulation preferentially activates emotion-related brain regions compared to painful skin stimulation

Skin pain and muscle pain are categorically distinct from each other. While skin pain is a sharp, spatially localized sensation, muscle pain is a dull, poorly localized and more unpleasant one. We hypothesized that there are specific brain regions preferentially activated by muscle pain compared to skin pain. To test this hypothesis, brain responses were recorded from 13 normal male subjects in response to repeated painful electrical stimulation of the muscle and skin of the left leg, using 3-T magnetic resonance imaging scanner. The common brain regions that responded to painful stimulations of both skin and muscle were the thalamus, anterior cingulate cortex, bilateral insula, contralateral primary and secondary somatosensory cortices, and ipsilateral cerebellum. Brain regions specifically activated by muscle stimulation were the midbrain, bilateral amygdala, caudate, orbitofrontal cortex, hippocampus, parahippocampus and superior temporal pole, most of which are related to emotion. Regions except the midbrain showed contralateral preference. These results suggest that dull sensation, which is characteristic of muscular pain, is related with processing in these brain regions.     

Tinnitus, diminished sound-level tolerance, and elevated auditory activity in humans with clinically normal hearing sensitivity

Phantom sensations and sensory hypersensitivity are disordered perceptions that characterize a variety of intractable conditions involving the somatosensory, visual, and auditory modalities. We report physiological correlates of two perceptual abnormalities in the auditory domain: tinnitus, the phantom perception of sound, and hyperacusis, a decreased tolerance of sound based on loudness. Here, subjects with and without tinnitus, all with clinically normal hearing thresholds, underwent 1) behavioral testing to assess sound-level tolerance and 2) functional MRI to measure sound-evoked activation of central auditory centers. Despite receiving identical sound stimulation levels, subjects with diminished sound-level tolerance (i.e., hyperacusis) showed elevated activation in the auditory midbrain, thalamus, and primary auditory cortex compared with subjects with normal tolerance. Primary auditory cortex, but not subcortical centers, showed elevated activation specifically related to tinnitus. The results directly link hyperacusis and tinnitus to hyperactivity within the central auditory system. We hypothesize that the tinnitus-related elevations in cortical activation may reflect undue attention drawn to the auditory domain, an interpretation consistent with the lack of tinnitus-related effects subcortically where activation is less potently modulated by attentional state. The data strengthen, at a mechanistic level, analogies drawn previously between tinnitus/hyperacusis and other, nonauditory disordered perceptions thought to arise from neural hyperactivity such as chronic neuropathic pain and photophobia.     

Cortical responses to thermal pain depend on stimulus size: a functional MRI study

Cortical activity patterns to thermal painful stimuli of two different sizes were examined in normal volunteers using functional magnetic resonance imaging (fMRI). Seven right-handed subjects were studied when the painful stimulus applied to the right hand fingers covered either 1,074-mm(2)-area large stimulator or 21-mm(2)-area small stimulator. Stimulus temperatures were adjusted to give rise to equivalent moderately painful ratings. fMRI signal increases and decreases were determined for the contralateral parietal and motor areas. When the overall activity in these regions was compared across subjects, increased fMRI activity was observed over more brain volume with the larger stimulator, whereas decreased fMRI activity was seen in more brain volume for the smaller stimulator. The individual subject and group-averaged activity patterns indicated regional specific differences in increased and decreased fMRI activity. The small stimulator resulted in decreased fMRI responses throughout the upper body representation in both primary somatosensory and motor cortices. In contrast, no decreased fMRI signals were seen in the secondary somatosensory cortex and in the insula. In another seven volunteers, the effects of the size of the thermal painful stimulus on vibrotactile thresholds were examined psychophysically. Painful stimuli were delivered to the fingers and vibrotactile thresholds were measured on the arm just distal to the elbow. Consistent with the fMRI results in the primary somatosensory cortex, painful thermal stimuli using the small stimulator increased vibrotactile thresholds on the forearm, whereas similarly painful stimuli using the large stimulator had no effect on forearm vibrotactile thresholds. These results are discussed in relation to the cortical dynamics for pain perception and in relation to the center-surround organization of cortical neurons.     

Phantom Breast Syndrome

Phantom breast syndrome is a type of condition in which patients have a sensation of residual breast tissue and can include both non-painful sensations as well as phantom breast pain. The incidence varies in different studies, ranging from approximately 30% to as high as 80% of patients after mastectomy. It seriously affects quality of life through the combined impact of physical disability and emotional distress. The breast cancer incidence rate in India as well as Western countries has risen in recent years while survival rates have improved; this has effectively increased the number of women for whom post-treatment quality of life is important. In this context, chronic pain following treatment for breast cancer surgery is a significantly under-recognized and under-treated problem. Various types of chronic neuropathic pain may arise following breast cancer surgery due to surgical trauma. The cause of these syndromes is damage to various nerves during surgery. There are a number of assumed factors causing or perpetuating persistent neuropathic pain after breast cancer surgery. Most well-established risk factors for developing phantom breast pain and other related neuropathic pain syndromes are severe acute postoperative pain and greater postoperative use of analgesics. Based upon current evidence, the goals of prophylactic strategies could first target optimal peri-operative pain control and minimizing damage to nerves during surgery. There is some evidence that chronic pain and sensory abnormalities do decrease over time. The main group of oral medications studied includes anti-depressants, anticonvulsants, opioids, N-methyl-D-asparate receptor antagonists, mexilitine, topical lidocaine, cannabinoids, topical capsaicin and glysine antagonists. Neuromodulation techniques such as motor cortex stimulation, spinal cord stimulation, and intrathecal drug therapies have been used to treat various neuropathic pain syndromes.     

Analysis of synchrony demonstrates that the presence of “pain networks” prior to a noxious stimulus can enable the perception of pain in response to that stimulus

Our previous study has shown that directed attention to a painful stimulus is associated with increased synchrony between electrocorticographic (ECoG) oscillations in pain-related cortical structures. We now test the hypothesis that the synchrony or functional connectivity of this pain network differs between events during which pain is or is not perceived (pain or non-pain events) in response to a noxious cutaneous laser stimulus. ECoG recordings were made through subdural electrodes implanted in a patient for the treatment of epilepsy. The patient was instructed that the stimulus could be painful or non-painful on any given presentation. Synchrony between ECoG signals at different sites was measured during the pre-stimulus interval, and the difference in the number of sites with significant pre-stimulus synchrony was compared between pain and non-pain events. Pre-stimulus synchrony was more common during pain versus non-pain events among electrodes overall, and in the subset of electrodes at which laser-evoked potentials (LEPs) were recorded. This difference between pain and non-pain events was also significant for the subset of electrodes over medial cortex, including anterior cingulate cortex (ACC), but not for subsets of electrodes over the superior and inferior convexity, including primary somatosensory (S1) and parasylvian cortex (PS), respectively. These results suggest that dynamic changes in the functional connectivity between ACC and other cortical regions enable the perception of pain in response to noxious stimuli. Supported by a grant from the NIH (RO1 NS38493) to FAL.     

Perception of pain coincides with the spatial expansion of electroencephalographic dynamics in human subjects

The dynamics of cortex driven by painful median nerve stimulation were investigated in event-related oscillation (ERO). We applied a wavelet time-frequency analysis to differentiate the brain dynamics between painful and non-painful somatosensory stimulation. The observed pattern to pain-induced effects exhibited a stepwise decrease of frequencies over time, starting around 26 ms over somatosensory cortex at 80 Hz, intermediate oscillations at 40 and 20 Hz around 40 ms, and reaching down to 10 Hz after 160 ms. This step-wise frequency decrease of ERO, coincident with spatial shift from the contralateral somatosensory area at 80 Hz to the centro-frontal brain at 40/20 Hz and final spatial expansion to the large region of centro-parietal areas at 10 Hz, may represent the cortical processes necessary to transfer sensory information from perceptual stages to subsequent cognitive stages in consciousness.     

Hemispheric lateralization of somatosensory processing

Processing of both painful and nonpainful somatosensory information is generally thought to be subserved by brain regions predominantly contralateral to the stimulated body region. However, lesions to right, but not left, posterior parietal cortex have been reported to produce a unilateral tactile neglect syndrome, suggesting that components of somatosensory information are preferentially processed in the right half of the brain. To better characterize right hemispheric lateralization of somatosensory processing, H(2)(15)O positron emission tomography (PET) of cerebral blood flow was used to map brain activation produced by contact thermal stimulation of both the left and right arms of right-handed subjects. To allow direct assessment of the lateralization of activation, left- and right-sided stimuli were delivered during separate PET scans. Both innocuous (35 degrees C) and painful (49 degrees C) stimuli were employed to determine whether lateralized processing occurred in a manner related to perceived pain intensity. Subjects were also scanned during a nonstimulated rest condition to characterize activation that was not related to perceived pain intensity. Pain intensity-dependent and -independent changes in activation were identified in separate multiple regression analyses. Regardless of the side of stimulation, pain intensity--dependent activation was localized to contralateral regions of the primary somatosensory cortex, secondary somatosensory cortex, insular cortex, and bilateral regions of the cerebellum, putamen, thalamus, anterior cingulate cortex, and frontal operculum. No hemispheric lateralization of pain intensity-dependent processing was detected. In sharp contrast, portions of the thalamus, inferior parietal cortex (BA 40), dorsolateral prefrontal cortex (BA 9/46), and dorsal frontal cortex (BA 6) exhibited right lateralized activation during both innocuous and painful stimulation, regardless of the side of stimulation. Thus components of information arising from the body surface are processed, in part, by right lateralized systems analogous to those that process auditory and visual spatial information arising from extrapersonal space. Such right lateralized processing can account for the left somatosensory neglect arising from injury to brain regions within the right cerebral hemisphere.     

Cortical responses to noxious stimuli during sleep

We used magnetoencephalography to study effects of sleep on cortical responses to noxious stimuli and to clarify the mechanisms underlying pain perception. For a noxious stimulus, painful intra-epidermal electrical stimulation, which selectively activates A-delta fibers, was applied to the dorsum of the left hand. While awake, subjects were asked to count the number of stimuli silently (Attention) or ignore the stimuli (Control). During sleep, magnetic fields recorded in stage 1 sleep and stage 2 sleep were analyzed. One main component at a latency around 140-160 ms was identified in the awake condition. Multiple source analysis indicated that this main component was generated by activities in the contralateral primary somatosensory cortex (SI), bilateral secondary somatosensory cortex (SII) and insular cortex. The medial temporal area (MT) and cingulate cortex were activated later than the main component. Cortical responses in the contralateral SI, ipsilateral SII and MT, bilateral insula and cingulate cortex were significantly enhanced in Attention as compared with Control. The main component 1 M as well as later magnetic fields were markedly attenuated during sleep, suggesting that all these cortical areas are involved in pain cognition.     

Scalp Field Potentials of Human Pain: Spatial Effects and Temporal Relation in Finger Stimulation

Summary In the present study, the spatial extent and temporo-spatial correlations of the human brain responses were investigated by electrically stimulating thumb (D1) and little finger (D5) under painful and non-painful intensity levels. High-density (124-ch) somatosensory evoked potentials (SEPs) were recorded (-50 to +450 ms) from 15 healthy male volunteers. Early (0-50 ms), and late phases (150-450 ms) of the responses were analyzed. Peak stages 33 ms, 42 ms, 210 ms, 328 ms for D1; and 33 ms, 44 ms, 240 ms, 350 ms for D5 were isolated from a compressed waveform; the relationships within stages and phases were investigated using topography, Focal maximum Amplitude (FA, single central site at 0.2 cm²) and Area Magnitude (AM, summated FA and amplitudes of neighboring four sites in a region of nearly 9.9 cm² area). In the early phase, the response of FA at 33 ms was significantly higher during painful than non-painful stimulation for both D1 and D5. In the late phase D1 (210 ms and 328 ms), and D5 (240 ms and 350 ms) the spatial areas of activation were significantly enlarged from non-painful to painful stimulation. For temporo-spatial relationship, D1 at 33 ms of early phase showed a significant correlation between the negative maximal site (sink) and the positive maximal site (source) under both non-painful and painful stimulations. For the late phase, the AM potentials at N2 correlated with that of P2 for both D1 and D5 under painful stimulation. The focal effects in FA of contralateral early potential indicates a shallow dipole in the primary somatosensory area of SI, while the large spatial extent in AM indicates a deep dipole of the putative cingulum activation under painful stimulation. No correlation between early and late activities implied that both activations are operated independently at the early SI and late cingulate processing of evoked pain.     

Somatosensory mu activity reflects imagined pain intensity of others

In accordance with simulation theories of empathy, the somatosensory cortex is involved in the perception of pain of others. Cognitive processes, like perspective taking, can alter empathy‐related activity within the somatosensory cortex. The current study investigates whether this modulation is caused by the imagined sensation of pain or by the cognitive load of a perspective‐taking task. Applying a within‐subject design, participants (N = 30) watched pictures of painful and nonpainful actions, while imagining reduced, normal, or increased pain perception of the observed individual. Mu activity (8–13 Hz), which is inversely correlated with sensorimotor‐cortex activity, was measured via EEG. To calculate mu activity (central electrodes) and alpha activity (occipital electrodes), which served as a control for effects of cognitive load, a fast Fourier transform was applied. Mu suppression linearly increased from reduced to normal to increased imagined pain (p < .05), while alpha activity was unaffected by the imagined pain (p > .80). Suppression of the 8–13 Hz band at central and occipital electrodes was stronger in response to painful actions compared to nonpainful actions (p < .01). These results indicate that modulation of mu activity through perspective taking reflects the imagined pain intensity and not the cognitive load induced by the task.     

Olfactory and trigeminal interaction of menthol and nicotine in humans

The purpose of the study was to investigate the interactions between two stimuli—menthol and nicotine—both of which activate the olfactory and the trigeminal system. More specifically, we wanted to know whether menthol at different concentrations modulates the perception of burning and stinging pain induced by nicotine stimuli in the human nose. The study followed an eightfold randomized, double-blind, cross-over design including 20 participants. Thirty phasic nicotine stimuli at one of the two concentrations (99 and 134 ng/mL) were applied during the entire experiment every 1.5 min for 1 s; tonic menthol stimulation at one of the three concentrations (0.8, 1.5 and 3.4 μg/mL) or no-menthol (placebo control conditions) was introduced after the 15th nicotine stimulus. The perceived intensities of nicotine’s burning and stinging pain sensations, as well as perceived intensities of menthol’s odor, cooling and pain sensations, were estimated using visual analog scales. Recorded estimates of stinging and burning sensations induced by nicotine initially decreased (first half of the experiment) probably due to adaptation/habituation. Tonic menthol stimulation did not change steady-state nicotine pain intensity estimates, neither for burning nor for stinging pain. Menthol-induced odor and cooling sensations were concentration dependent when combined with low-intensity nicotine stimuli. Surprisingly, this dose dependency was eliminated when combining menthol stimuli with high-intensity nicotine stimuli. There was no such nicotine effect on menthol’s pain sensation. In summary, we detected interactions caused by nicotine on menthol perception for odor and cooling but no effect was elicited by menthol on nicotine pain sensation.     

A comparative magnetoencephalographic study of cortical activations evoked by noxious and innocuous somatosensory stimulations

We recorded somatosensory-evoked magnetic fields and potentials produced by painful intra-epidermal stimulation (ES) and non-painful transcutaneous electrical stimulation (TS) applied to the left hand in 12 healthy volunteers to compare cortical responses to noxious and innocuous somatosensory stimulations. Our results revealed that cortical processing following noxious and innocuous stimulations was strikingly similar except that the former was delayed approximately 60 ms relative to the latter, which was well explained by a difference in peripheral conduction velocity mediating noxious (Adelta fiber) and innocuous (Abeta fiber) inputs. The first cortical activity evoked by both ES and TS was in the primary somatosensory cortex (SI) in the hemisphere contralateral to the stimulated side. The following activities were in the bilateral secondary somatosensory cortex (SII), insular cortex, cingulate cortex, anterior medial temporal area and ipsilateral SI. The source locations did not differ between the two stimulus modalities except that the dipole for insular activity following ES was located more anterior to that following TS. Both ES and TS evoked vertex potentials consisting of a negativity followed by a positivity at a latency of 202 and 304 ms, and 134 and 243 ms, respectively. The time course of the vertex potential corresponded to that of the activity of the medial temporal area. Our results suggested that cortical processing was similar between noxious and innocuous stimulation in SI and SII, but different in insular cortex. Our data also implied that activities in the amygdala/hippocampal formation represented common effects of noxious and tactile stimulations.     

Motor control over the phantom limb in above-elbow amputees and its relationship with phantom limb pain

Recent evidence shows that the primary motor cortex continues to send motor commands when amputees execute phantom movements. These commands are retargeted toward the remaining stump muscles as a result of motor system reorganization. As amputation-induced reorganization in the primary motor cortex has been associated with phantom limb pain we hypothesized that the motor control of the phantom limb would differ between amputees with and without phantom limb pain. Eight above-elbow amputees with or without pain were included in the study. They were asked to produce cyclic movements with their phantom limb (hand, wrist, and elbow movements) while simultaneously reproducing the same movement with the intact limb. The time needed to complete a movement cycle and its amplitude were derived from the kinematics of the intact limb. Electromyographic (EMG) activity from different stump muscles and from the homologous muscles on the intact side was recorded. Different EMG patterns were recorded in the stump muscles depending on the movement produced, showing that different phantom movements are associated with distinct motor commands. Phantom limb pain was associated with some aspects of phantom limb motor control. The time needed to complete a full cycle of a phantom movement was systematically shorter in subjects without phantom limb pain. Also, the amount of EMG modulation recorded in a stump muscle during a phantom hand movement was positively correlated with the intensity of phantom limb pain. Since phantom hand movement–related EMG patterns in above-elbow stump muscles can be considered as a marker of motor system reorganization, this result indirectly supports the hypothesis that amputation-induced plasticity is associated with phantom limb pain severity. The discordance between the (amputated) hand motor command and the feedback from above-elbow muscles might partially explain why subjects exhibiting large EMG modulation during phantom hand movement have more phantom limb pain.