The human operculo-insular cortex is pain-preferentially but not pain-exclusively activated by trigeminal and olfactory stimuli

Increasing evidence about the central nervous representation of pain in the brain suggests that the operculo-insular cortex is a crucial part of the pain matrix. The pain-specificity of a brain region may be tested by administering nociceptive stimuli while controlling for unspecific activations by administering non-nociceptive stimuli. We applied this paradigm to nasal chemosensation, delivering trigeminal or olfactory stimuli, to verify the pain-specificity of the operculo-insular cortex. In detail, brain activations due to intranasal stimulation induced by non-nociceptive olfactory stimuli of hydrogen sulfide (5 ppm) or vanillin (0.8 ppm) were used to mask brain activations due to somatosensory, clearly nociceptive trigeminal stimulations with gaseous carbon dioxide (75% v/v). Functional magnetic resonance (fMRI) images were recorded from 12 healthy volunteers in a 3T head scanner during stimulus administration using an event-related design. We found that significantly more activations following nociceptive than non-nociceptive stimuli were localized bilaterally in two restricted clusters in the brain containing the primary and secondary somatosensory areas and the insular cortices consistent with the operculo-insular cortex. However, these activations completely disappeared when eliminating activations associated with the administration of olfactory stimuli, which were small but measurable. While the present experiments verify that the operculo-insular cortex plays a role in the processing of nociceptive input, they also show that it is not a pain-exclusive brain region and allow, in the experimental context, for the interpretation that the operculo-insular cortex splay a major role in the detection of and responding to salient events, whether or not these events are nociceptive or painful.     

Synthetic heat at mild temperatures

"Synthetic heat", also known as the heat grill illusion, occurs when contact with spatially adjacent warm and cold stimuli produce a sensation of "heat". This phenomenon has been explained as a painful perception that occurs when warm stimulation inhibits cold-sensitive neurons in the spinothalamic tract (STT), which in turn unmasks activity in the pain pathway caused by stimulation of C-polymodal nociceptors (CPNs). The "unmasking model" was tested in experiment 1 by combining warm (35-40 degrees C) and cool (> or = 27 degrees C) stimuli that were too mild to stimulate CPNs. After discovering that these temperatures produced nonpainful heat, experiment 2 was designed to determine whether heat could be induced when near-threshold cooling was paired with mild warmth, and whether lowering the base temperature for cooling would increase the noxious (burning, stinging) components of heat for fixed cooling steps of 1-3 degrees C. Cooling by just 1 degrees C from a base temperature of 33 degrees C led to reports of heat on more than 1/3 of trials, and cooling by just 3 degrees C evoked heat on 75% of trials. Lowering the base temperature to 31 or 29 degrees C increased reports of heat and burning but did not produce significant reports of pain. Perception of nonpainful heat at such mild temperatures indicates either that cold-sensitive nociceptors with thresholds very similar to cold fibers innervate hairy skin in humans, or that heat can result from integration of warm fiber and cold fiber activity, perhaps via convergence on nonspecific (e.g., WDR) neurons in the STT.     

Functional brain mapping of pain perception

In this review, we summarize the contribution of functional imaging to the question of nociception in humans. In the beginning of the 90's, brain areas supposed to be involved in physiological pain processes were almost exclusively the primary somatosensory area (SI), thalamus, and anterior cingulate cortex. In spite of these a priori hypotheses, the first imaging studies revealed that the main brain areas and those providing the most consistent activations in pain conditions were the insular and the SII cortices, bilaterally. This has been confirmed with other techniques such as intracerebral recordings of evoked potentials after nociceptive stimulations with laser showing a consistent response in the operculo-insular area which amplitude correlates with pain intensity. In spite of electrode implantations in other areas of the brain, only rare and inconsistent responses have been found outside the operculo-insular cortices. With electrical stimulation delivered directly in the brain, it has also been shown that stimulation in this area only--and not in other brain areas--was able to elicit a painful sensation. Thus, over the last 15 years, the operculo-insular cortex has been re-discovered as a main area of pain integration, mainly in its sensory and intensity aspects. In neuropathic pain also, these areas have been demonstrated as being abnormally recruited, bilaterally, in response to innocuous stimuli. These results suggest that plastic changes may occur in brain areas that were pre-defined for generating pain sensations. Conversely, when the brain activations concomitant to pain relief is taken into account, a large number of studies pointed out medial prefrontal and rostral cingulate areas as being associated with pain controls. Interestingly, these activations may correlate with the magnitude of pain relief, with the activation of the PAG, and, at least in some instances, with the involvement of endogenous opioids.     

Synthetic heat at mild temperatures

"Synthetic heat", also known as the heat grill illusion, occurs when contact with spatially adjacent warm and cold stimuli produce a sensation of "heat". This phenomenon has been explained as a painful perception that occurs when warm stimulation inhibits cold-sensitive neurons in the spinothalamic tract (STT), which in turn unmasks activity in the pain pathway caused by stimulation of C-polymodal nociceptors (CPNs). The "unmasking model" was tested in experiment 1 by combining warm (35-40°C) and cool ( &#83 27°C) stimuli that were too mild to stimulate CPNs. After discovering that these temperatures produced nonpainful heat, experiment 2 was designed to determine whether heat could be induced when near-threshold cooling was paired with mild warmth, and whether lowering the base temperature for cooling would increase the noxious (burning, stinging) components of heat for fixed cooling steps of 1-3°C. Cooling by just 1°C from a base temperature of 33°C led to reports of heat on more than 1/3 of trials, and cooling by just 3°C evoked heat on 75% of trials. Lowering the base temperature to 31 or 29°C increased reports of heat and burning but did not produce significant reports of pain. Perception of nonpainful heat at such mild temperatures indicates either that cold-sensitive nociceptors with thresholds very similar to cold fibers innervate hairy skin in humans, or that heat can result from integration of warm fiber and cold fiber activity, perhaps via convergence on nonspecific (e.g., WDR) neurons in the STT.     

Multimodal assessment of pain in the esophagus: a new experimental model

A new multimodal pain assessment model was developed integrating electrical, mechanical, cold, and warmth stimuli into the same device. The device, with a bag and electrodes for electrical stimulation, was positioned in the lower part of the esophagus in 11 healthy subjects. Mechanical stimuli were delivered with an impedance planimetric system. Thermal stimuli were performed by circulating water of different temperatures (5-50 degrees C) inside the bag. All subjects reported both nonpainful and painful local and referred sensations to all stimuli. Temporal summation to repeated electrical stimuli could be studied. For all stimuli, there was a relationship between stimulus intensity and pain intensity. The referred pain area increased with increasing intensity of the electrical and mechanical stimuli. There were several differences between the sensations evoked by the four stimulus modalities, indicating activation of different visceral nerve pathways. This model offers the possibility for controlled multimodal stimuli activating the superficial and deeper layers of the human gut and should be used in basic, clinical, and pharmacological pain studies.     

Psychophysical Investigations into the Role of Low-Threshold C Fibres in Non-Painful Affective Processing and Pain Modulation

We recently showed that C low-threshold mechanoreceptors (CLTMRs) contribute to touch-evoked pain (allodynia) during experimental muscle pain. Conversely, in absence of ongoing pain, the activation of CLTMRs has been shown to correlate with a diffuse sensation of pleasant touch. In this study, we evaluated (1) the primary afferent fibre types contributing to positive (pleasant) and negative (unpleasant) affective touch and (2) the effects of tactile stimuli on tonic muscle pain by varying affective attributes and frequency parameters. Psychophysical observations were made in 10 healthy participants. Two types of test stimuli were applied: stroking stimulus using velvet or sandpaper at speeds of 0.1, 1.0 and 10.0 cm/s; focal vibrotactile stimulus at low (20 Hz) or high (200 Hz) frequency. These stimuli were applied in the normal condition (i.e. no experimental pain) and following the induction of muscle pain by infusing hypertonic saline (5%) into the tibialis anterior muscle. These observations were repeated following the conduction block of myelinated fibres by compression of sciatic nerve. In absence of muscle pain, all participants reliably linked velvet-stroking to pleasantness and sandpaper-stroking to unpleasantness (no pain). Likewise, low-frequency vibration was linked to pleasantness and high-frequency vibration to unpleasantness. During muscle pain, the application of previously pleasant stimuli resulted in overall pain relief, whereas the application of previously unpleasant stimuli resulted in overall pain intensification. These effects were significant, reproducible and persisted following the blockade of myelinated fibres. Taken together, these findings suggest the role of low-threshold C fibres in affective and pain processing. Furthermore, these observations suggest that temporal coding need not be limited to discriminative aspects of tactile processing, but may contribute to affective attributes, which in turn predispose individual responses towards excitatory or inhibitory modulation of pain.     

Activation of a distributed somatosensory cortical network in the human brain: a dipole modelling study of magnetic fields evoked by median nerve stimulation. Part II: effects of stimulus rate,attention and stimulus detection

In this study we used a repeated measures design and univariate analysis of variance to study the respective effects of ISI, spatial attention and stimulus detection on the strengths of the sources previously identified by modelling SEFs during the 200 ms following mentally counted left median nerve stimuli delivered at long and random ISIs (Part I). We compared the SEF source strengths in response to frequent and rare stimuli, both in detection and ignoring conditions. This permitted us to establish a hierarchy in the effects of ISI, attention and stimulus detection on the activation of the cortical network of SEF sources distributed in SI and posterior parietal cortex contralateral to stimulation, and in the parietal operculum (SII) and premotor frontal cortex of both hemispheres. In all experimental conditions the SI and parietal opercular sources were the most active. All sources were more active in response to stimuli delivered at long and random ISIs and the frontal sources were activated only in this condition of stimulation. Driving the subject's attention toward the side stimulated had no detectable effect on the activity of SEF sources at short ISI. At long ISIs mental counting of the stimuli increased the responses of all sources except SI. These results suggest that activation of frontal sources during mental counting could reflect a working memory process, and that of posterior parietal sources a spatial attention effect detectable only at long ISIs.     

Pain-related somatosensory evoked potentials following CO2 laser stimulation in man

0ain-related somatosensory evoked potentials (SEPs) following CO₂ laser stimulation were analyzed in normal volunteers. Low power and long wavelength CO₂ laser stimuli to the hand induced a sharp pain which was associated with a large positive component, P320, recorded over the scalp. Amplitude decreased and latency increased with reduction in stimulus intensity and subjective pain feeling. P320 was maximal at the vertex but was distributed widely over the scalp. There were no topographic differences between left- and right-hand stimulation, or between hand and chest stimulation. Lidocaine injection to produce anesthetic nerve block resulted in loss of P320, but the potential was relatively preserved during ischemic nerve block. No potential corresponding to P320 could be recorded following electrical or mechanical tactile stimulation.We consider P320 to be generated by impulses arising from pain stimuli and ascending through Aδ fibers. We propose the thalamus as a generator source from considering its scalp topography, but pain-specific cognition or perception may also be involved in generating this potential.     

Comparing sensibility for touch,cold, and warmth in different skin areas

The primary objective of this pilot study was to assess if the magnitude estimation of suprathreshold brushing, warmth (40?°C), and cold (25?°C) stimuli of the skin over the dorsum of the hand and the dorsum of the foot are comparable to the perceived intensity for the same stimuli applied to the skin over any of the following areas: forehead, m. trapezius, m. deltoideus, thoracic back, and lumbar back, respectively. Thirty-two subjects aged 18–64 years were included. Participants were examined by two physicians on two different occasions, 1–58 days apart. Participants rated the magnitude of the perceived sensation of each stimulus on an 11-point numerical rating scale (NRS) 0–10, where 0 was anchored to “no sensation at all for touch/cold/warmth” and 10 anchored to “the most intense imaginable non-painful sensation of touch/cold/warmth”. The criterion for sensory equivalence for one modality was arbitrarily considered satisfactory if two regions had the same numerical rating ±1 point in at least 85% of the individuals. Based on the pre-study criteria for sensory equivalence applied in this study only one area was found to be equivalent to the foot skin for the percept of brushing, that is, the skin over the deltoid muscle and one area for the hand, that is, the skin over the forehead. We failed to find any area with equivalent sensitivity to the hand or the foot for the cold or warm stimuli.     

Effect of chronic intermittent exposure to AM radiofrequency field on responses to various types of noxious stimuli in growing rats

There are several reports of altered pain sensation after exposure (from a few minutes to hours in single or repeated doses for 2-3 weeks) to electromagnetic fields (EMF) in adults. The commonly utilized noxious stimulus is radiant heat. The nociceptive responses are known to be influenced by characteristics of stimulus, organism, and environment. We studied the pattern of nociceptive responses to various noxious stimuli in growing rats exposed to radiofrequency field (73.5 MHz amplitude modulated, 16 Hz power density 1.33 mw/cm(2), SAR = 0.4 w/kg) for 45 d (2 h/d). Threshold current for stimulation of nociceptive afferents to mediate motor response of tail (TF), vocalization during stimulus (VD), and vocalization after discharge (VA); the withdrawal latency of tail (TFL) and hind paw (HPL) to thermal noxious stimulus and tonic pain responses were recorded in every rat. The TFL was not affected, HPL was decreased (p < 0.01), and the thresholds of TF and VD were not affected, while, that of VA was significantly decreased. The tonic pain rating was decreased (p < 0.01). A decrease in the threshold of VA (p < 0.01) is indicative of an increase in the emotional component of the response to the phasic pain, whereas a decrease in the pain rating indicates analgesia in response to the tonic pain. The results of our study suggest that chronic (45 d), intermittent (2 h/d) amplitude modulated RF field exposure to the peripubertal rat increases the emotional component of phasic pain over a basal eaualgesic state, while late response to tonic pain is decreased. The data suggest that amplitude modulated RF field differentially affects the mechanisms involved in the processing of various noxious stimuli.     

The influence of rate of temperature change and peak stimulus duration on pain intensity and quality

An important aspect of experimental pain research is that the assessment methods can investigate the different aspects of pain perception. The aim of the present study was to investigate the influence of rate of temperature change and peak stimulus duration on heat evoked pain intensity and quality. All stimuli were applied within the medial aspect of the anterior forearm. The rate of temperature change was varied from 1 to 16 C/s without any effect on the pain threshold. The pain threshold decreased with an increasing peak stimulus duration from 0.1 to 2 s, but not from 2 to 3 s. The pain intensity for suprathreshold stimuli (46 C, 48 C, 50 C) increased for decreasing rates and increasing duration. The pain intensity was highly correlated with the energy of the stimulus. When the rates of temperature change (1-16 C/s) are varied, no differences between pricking and burning pain were present at either low stimulus intensity (46 C) or high stimulus intensity (50 C). At low stimulus intensity (46 C), the pricking pain was not influenced by the duration (0.1-3 s), but the burning pain was intensified when the duration was increased from 1.5 to 3 s. At high intensity stimuli (50 C), the pricking pain intensified with an increased duration, whereas burning pain did not. The heat pain threshold is influenced by the peak stimulus duration, and not by the rate of temperature change. If suprathreshold stimuli are used, both the rate of temperature change and the peak stimulus duration can strongly affect the pain intensity and the pain quality. Therefore, the same stimulus modality can be used to assess the modulation of different pain intensities and of the pricking and burning pain qualities simply by varying the stimulus configuration.     

Modification of Electrical Pain Threshold by Voluntary Breathing-Controlled Electrical Stimulation (BreEStim) in Healthy Subjects

Background

Pain has a distinct sensory and affective (i.e., unpleasantness) component. BreEStim, during which electrical stimulation is delivered during voluntary breathing, has been shown to selectively reduce the affective component of post-amputation phantom pain. The objective was to examine whether BreEStim increases pain threshold such that subjects could have improved tolerance of sensation of painful stimuli.

Methods

Eleven pain-free healthy subjects (7 males, 4 females) participated in the study. All subjects received BreEStim (100 stimuli) and conventional electrical stimulation (EStim, 100 stimuli) to two acupuncture points (Neiguan and Weiguan) of the dominant hand in a random order. The two different treatments were provided at least three days apart. Painful, but tolerable electrical stimuli were delivered randomly during EStim, but were triggered by effortful inhalation during BreEStim. Measurements of tactile sensation threshold, electrical sensation and electrical pain thresholds, thermal (cold sensation, warm sensation, cold pain and heat pain) thresholds were recorded from the thenar eminence of both hands. These measurements were taken pre-intervention and 10−min post-intervention.

Results

There was no difference in the pre-intervention baseline measurement of all thresholds between BreEStim and EStim. The electrical pain threshold significantly increased after BreEStim (27.5±6.7% for the dominant hand and 28.5±10.8% for the non-dominant hand, respectively). The electrical pain threshold significantly decreased after EStim (9.1±2.8% for the dominant hand and 10.2±4.6% for the non–dominant hand, respectively) (F_{[1, 10]} = 30.992, p = .00024). There was no statistically significant change in other thresholds after BreEStim and EStim. The intensity of electrical stimuli was progressively increased, but no difference was found between BreEStim and EStim.

Conclusion

Voluntary breathing controlled electrical stimulation selectively increases electrical pain threshold, while conventional electrical stimulation selectively decreases electrical pain threshold. This may translate into improved pain control.     

Thermal perception thresholds recorded using method of limits change over brief time intervals

Quantitative Sensory Testing (QST) of thermal perception thresholds assesses small afferent nerve function. QST has also been widely used to investigate the effects of interventions on the perception of activity within these nerve fibres, often over brief time periods. The natural variation in perception thresholds over brief time periods has not been determined, however, complicating accurate identification of induced changes. The present study therefore investigated changes in thermal perception threshold values within a 1-h period. Twenty-four healthy women volunteers aged 18-28 years (mean 20.6, SD 2.8) undertook cold sensation (CS), warm sensation (WS), cold pain (CP), and hot pain (HP) perception threshold measurements on the thenar eminence of the dominant hand during six 8-min experimental cycles. The order of stimulus presentation was randomized within pre-selected criteria. An adaptation temperature of 32 degrees C, a rate of temperature change of 0.5 degrees C/s, a 3 cm x 3 cm thermode, and a method of limits algorithm were used. Separate two-way ANOVAs with repeated measures showed statistically significant changes over time for WS, CS, and HP (p < 0.05), but not for CP (p = 0.232). The results indicate that WS, CS, and HP perception thresholds change significantly with repeated testing over a 1-h period. These results should be carefully considered when assessing the importance of observed changes in thermal perception thresholds. In research trials exclusion of a control group would be a fundamental flaw.     

Afferent Modulation of Warmth Sensation and Heat Pain in the Human Hand

The hands of 14 normal humans were used to determine the somatotopic organization of the modulation of warmth sensation and heat pain by different forms of cutaneous stimuli. Test stimuli were 5-sec heat pulses ranging from 36° to 51°C, delivered to the fingerpads of digits 1, 2, 4, and 5 with a contact thermode. Conditioning stimuli (15 sec) bracketed the test stimuli and included vibration, noxious and innocuous heat, cold, and electrical pulses delivered to the fingerpads of digits that were adjacent or nonadjacent to the tested digits. Noxious (48° ± 1.3°C), but not innocuous (43°C), heat stimuli increased the perceived magnitude estimation of innocuous test stimuli (36–43°C) by 20–37% when delivered to adjacent, but not to nonadjacent, digits. No other conditioning stimuli had any effect on the intensity of warmth perception. In contrast, both noxious and innocuous heat or electrical conditioning reduced the magnitude estimation of noxious (50–5°C), but not innocuous, test pulses by 12–22% when delivered to adjacent digits. Conditioning of nonadjacent digits was significantly less effective. The analgesic effects of noxious and innocuous conditioning were approximately equal. Vibratory (120 Hz, 3.5 μm) and cold (15°C) conditioning stimuli were ineffective. The results are consistent with a dermatomal somatotopic organization of tactile and heat modulatory influences on warmth sensation and heat pain. The results further suggest that the neural mechanisms subserving warmth mediate a negative feedback influence on heat pain intensity.     

Laser-evoked brain potentials in patients with dissociated loss of pain and temperature sensibility

Brief heat stimuli, elicited by a CO₂ laser (10.6 μm wave length), activate the most superficial cutaneous nerve terminals of the thin myelinated Aδ and unmyelinated C fibres which mediate heat and pain sensations. This paper investigates late cerebral potentials (SEPs) in response to laser pulses in comparison with those to conventional electrical stimulation in 18 patients with a dissociated sensory deficit (intact mechanosensibility and disturbed temperature and pain sensation). Patients were stimulated in the most disturbed limb (affected area) and in a corresponding control area.In all 18 patients the SEPs elicited by laser stimuli were able to identify the body site with heaviest disturbances in pain and thermosensibility: the SEPs from the affected area were reduced or delayed, compared to the control area. In contrast, no alterations in SEPs could be observed after conventional electrical nerve stimulation, in agreement with the normal mechanosensibility. However, the degree of SEP modulation in response to cutaneous heat stimuli did not correspond to the severity of the subjectively reported sensory deficit. Highest correlations between sensory deficits and abnormal SEPs were found in all those patients in whom computer tomography or MR imaging documented a localized destructive process in the CNS. All patients with the smallest SEP modulations despite a considerable sensory deficit had an inflammatory aetiology. Preliminary criteria to define a laser-evoked SEP as pathological are discussed.     

Responses of cells in the somatosensory cortex of unanaesthetized cats after sinusoidal displacements of single vibrissae

Summary Neurones in the somatosensory cortex of unanaesthetized restrained cats were recorded during single trapezoid and repetitive sinusoidal displacements of single vibrissae. Responses to trapezoid displacements were similar to those described previously in anaesthetized cats (Hellweg et al., 1977).During repetitive mechanical stimulation cortical cells showed adaptive behaviour so that at higher stimulation frequencies the number of cell discharges per stimulus cycle decreased. The ability to follow the repetition of the stimulus at a one to one ratio was lost in the frequency range between 20 Hz and 60 Hz. A few exceptional cells, while not following at a one to one ratio, still showed some periodicities in their response histograms corresponding to repetition rates of up to 100 Hz. In about 10% of the cells nonmonotonic functions between stimulation frequency and response per cycle were found. These nonmonotonic functions as well as the different adaptive behaviour of cells could not be predicted on the basis of their response to trapezoid stimuli.Measurements of the phase differences between stimulus cycle and response peaks during repetitive stimulation showed that both can vary as a function of stimulation frequency. It is discussed whether these findings could be compatible with the concept of phase coding in the somatosensory cortex.     

Comparative psychophysical characteristics of cutaneous CO2 laser and contact heat stimulation

Psychophysical visual analog scaling can be used to reveal critical determinants of the neural processing underlying non-painful and painful heat sensations produced by radiant and contact heat stimulation. This study determined the stimulus-response (S-R) functions of cutaneous non-painful and painful heat stimuli delivered by an infra-red CO2 laser or by a contact thermode in a series of experiments in healthy volunteers. In experiment 1 ( n = 12), with the rating scale anchored at pain threshold, the S-R curve for brief (60 ms) laser pulse stimulation with a beam diameter of 10 mm was a negatively accelerating function. Transformation of laser stimulus intensity (W) into temperatures ( C) did not change the form of the S-R curve. In experiment 2 ( n=9), using the same laser stimulus parameters as in experiment 1, but without an anchored rating scale, the form of the S-R relationship did not change. In experiment 3 ( n =9), increases of the laser pulse duration up to 5 s and the beam diameter up to 18 mm produced linear S-R curves. In contrast, in experiment 4 ( n =21), the S-R curve for cutaneous contact heat stimuli applied for 5 s with an 18 mm diameter probe was best described by a positively accelerating power function with an exponent greater than 2.0. These experiments have (1) characterized the S-R functions for different parameters of infra-red laser stimulation of the skin, and (2) have shown that the form of the S-R function for innocuous and noxious heat sensation is influenced strongly by the physical conditions of heat stimulus application, including mechanical contact with the skin.     

Electrical stimulation of the posterior limb of the internal capsule for treatment of thalamic pain

Electrical stimulation of the posterior limb of the internal capsule was performed in 7 patients with thalamic pain who had developed dysesthesia, hyperpathia and/or spontaneous burning pain. Ramped bipolar stimulation elicited sensory responses, such as warm or comfortable sensation. Follow-up from 9 months to 2 years and 7 months showed that 3 patients had a good result, two had fair and the remaining two had poor results. No serious side effects were seen. The mechanism of pain relief by the internal capsule stimulation is discussed.     

Manipulation of the somatosensory cortex modulates stimulus-induced repetitive ear movements in a seizure-sensitive strain of gerbil

Some Mongolian gerbils (Meriones unguiculatus) respond to stimulation by seizures, the pattern of which changes progressively during development. We previously established a seizure-sensitive strain, MGS/Idr, in which all animals exhibit such stimulus-induced seizures. We have now noted that all adults of this strain also show repetitive backward movements of the ears at the ears at the beginning of stimulus-induced seizures, although the incidence varies with the individual. We examined whether the cerebral cortex was involved in these movements and found that electrical stimulation of an area of the somatosensory cortex elicited strong backward movement of the ear on the contralateral side, and that unilateral application of bicuculline, a GABAA receptor antagonist, induced spontaneous repetitive backward movements of the same ear. In this area, sharp waves appeared in the electrocortigram during the repetitive ear movements induced by seizure-inducing stimuli. Unilateral ablation of this area abolished stimulus-induced repetitive movements of the contralateral ear, but had no effects on those of the ipsilateral ear. These results suggest that, in certain types of seizure-susceptible subjects, it may be possible to modify stimulus-induced repetitive movements by manipulating a certain area of the somatosensory cortex which is related to these movements and that this gerbil strain may be useful in research on this subject.     

Chemo-somatosensory event-related potentials in response to repetitive painful chemical stimulation of the nasal mucosa

The aim of the study was to investigate how chemo-somatosensory event-related potentials (CSSERPs) and pain ratings are modified by repetitive painful stimulation of the nasal mucosa (58% v/v CO₂, 200 msec duration). Twenty-two subjects performed 3 experiments during which trains of stimuli were applied. The interstimulus interval (ISI) between stimuli was constant for each experiment, but varied between experiments (8, 4, and 2 sec). CSSERPs were obtained from positions (Fz, C3, Cz, C4, and Pz). The subjects not only rated the overall perceived intensities but also reported the quality of the stimuli. At an ISI of 8 sec estimates decreased and only stinging sensations were reported. In contrast, at an interval of 2 sec estimates increased being accompanied by the buildup of burning pain. This phenomenon was interpreted in terms of the superposition of first (sharp and stinging pain: Aδ fibers) and second pain (dull and burning pain: C fibers), respectively. However, given the special circumstances of short ISIs CSSERP amplitudes decreased the more the shorter the ISI was. In line with previous investigations it is hypothesised that CSSERPs predominantly reflect nociceptive information transmitted via Aδ fibers.