Cortical processing of visceral and somatic stimulation: differentiating pain intensity from unpleasantness

Visceral and somatic pain perception differs in several aspects: poor localization of visceral pain and the ability of visceral pain to be referred to somatic structures. The perception of pain intensity and affect in visceral and somatic pain syndromes is often different, with visceral pain reported as more unpleasant. To determine whether these behavioral differences are due to differences in the central processing of visceral and somatic pain, non-invasive imaging tools are required to examine the neural correlates of visceral and somatic events when the behavior has been isolated and matched for either unpleasantness or pain intensity. In this study we matched the unpleasantness of somatic and visceral sensations and imaged the neural representation of this perception using functional magnetic resonance imaging in 10 healthy right-handed subjects. Each subject received noxious thermal stimuli to the left foot and midline lower back and balloon distension of the rectum while being scanned. Stimuli were matched to the same unpleasantness rating, producing mild-moderate pain intensity for somatic stimuli but an intensity below the pain threshold for the visceral stimuli. Visceral stimuli induced deactivation of the perigenual cingulate bilaterally with a relatively greater activation of the right anterior insula-i.e. regions encoding affect. Somatic pain induced left dorso-lateral pre-frontal cortex and bilateral inferior parietal cortex activation i.e. regions encoding spatial orientation and assessing perceptual valence of the stimulus. We believe that the observed patterns of activation represent the differences in cortical process of interoceptive (visceral) and exteroceptive (somatic) stimuli when matched for unpleasantness.     

Prepulse inhibition of perceived stimulus intensity: paradigm assessment

In 1939, Helen Peak reported that the presentation of paired acoustic stimuli, separated by 177ms, resulted in a 25% reduction in the perceived intensity of the second stimulus. After 65 years, this form of prepulse inhibition of perceived stimulus intensity (PPIPSI) remains relatively less developed, compared to technically and analytically complex "gating" measures, e.g. PPI of startle and P50 event related potential (ERP) suppression. We report that unlike PPI, which can be observed at very brief inter-stimulus intervals (ISI's), PPIPSI requires ISI's >or=60ms. It exhibits significant test-retest stability over a 2-week period, does not exhibit sex differences or menstrual cyclicity, and is not significantly associated with personality dimensions of novelty seeking, harm avoidance, reward dependence or sensation seeking. PPIPSI is a robust, stable, parametrically sensitive and "low tech" measure of sensory gating that is relatively unaffected by a number of biological variables in normal individuals.     

Effects of prepulse intensity, duration, and bandwidth on perceived intensity of startling acoustic stimuli

Intense abrupt stimuli can elicit a startle reflex; a weak "prepulse" 30-300 ms earlier can reduce both startle and perceived stimulus intensity. Prepulse inhibition (PPI) of startle, an operational measure of sensorimotor gating, is used to understand brain disorders characterized by gating deficits. Compared to startle, PPI of perceived stimulus intensity (PPIPSI) may provide information that is distinct, and easier to acquire and analyze. To develop this experimental measure, we examined PPIPSI under different stimulus conditions. Both PPI and PPIPSI exhibited a non-linear relationship to prepulse intensity, with prepulses 15 dB(A) above background causing maximal inhibition of both measures. A 50 ms broadband noise prepulse produced maximal PPI and PPIPSI, whereas 5 and 20 ms pure tone prepulses produced maximal PPIPSI and PPI, respectively. PPIPSI is a robust, parametrically sensitive and "low tech" measure of sensory gating that may become a valuable tool for understanding the biology of certain mental disorders.     

Dynamic,but not static,pain sensitivity predicts exercise-induced muscle pain: Covariation of temporal sensory summation and pain intensity

Cross-section studies suggest that measures of pain sensitivity, derived from quantitative sensory testing (QST), are elevated in persons with chronic pain conditions. However, little is known about whether development of chronic pain is preceded by elevated pain sensitivity or pain sensitivity increases as a result of prolonged experience of pain. Here we used QST to test static (single suprathreshold stimuli) and dynamic (temporal sensory summation) pain processing of thermal stimuli. Muscle pain was induced using high-intensity exercise (DOMS). Multi-level modeling approaches determined the daily covariation among static and dynamic QST measures and pain intensity. Variation in responses to static pain sensitivity was not associated with pain intensity from DOMS while, in contrast, variation in dynamic pain sensitivity was positively associated with variation in pain intensity from DOMS. This finding supports the use of TSS as a marker of the central pain state and potentially as an appropriate measure for treatment monitoring.     

Effect of gentle cutaneous stimulation on heat-induced autonomic response and subjective pain intensity in healthy humans

The present study examined whether touch influences the autonomic responses and subjective pain intensity induced by noxious heat stimulation in humans. Heart rate and digital pulse wave were recorded. Heat stimulation was applied to the right plantar foot before, during, and after touch. Subjective pain intensity was evaluated using a visual analog scale (VAS). Touch was applied over the right medial malleolus for 10 min. Two types of touch were employed in a cross-over double-blinded randomized manner. When touch was applied with a soft elastomer brush, heat-induced autonomic responses attenuated significantly, while VAS scores were unchanged. In contrast, touch with a flat disc was ineffective for any measurement. Participants hardly perceived a difference in the texture of the touching materials. The present study result suggests there are mechanisms in conscious humans where some sort of touch inhibits nociceptive transmission into autonomic reflex pathways independent of sensation and cognition.     

The detection and perceived intensity of noxious thermal stimuli in monkey and in human

1. The magnitude of the sensations produced by small increases in thermal stimuli superimposed on noxious levels of heat stimulation was studied by the use of a simple reaction-time task. Noxious thermal stimuli were presented on the face of three monkeys, the forearm volar surface of three monkeys, and the face of four human subjects. The subject, either monkey or human, initiated a trial by pressing an illuminated button. Subsequently, a contact thermode increased in temperature from a base line of 38 degree C to temperatures of 44, 45, 46, or 47 degrees C (T1). After a variable time period lasting between 4 and 10 s, the thermode temperature increased an additional 0.1, 0.2, 0.4, 0.6, or 0.8 degrees C (T2). The subject was required to release the button as soon as the T2 stimulus was detected. Detection latency, expressed as its reciprocal, detection speed, was defined as the time interval between the onset of T2 and the release of the button. 2. The monkeys' detection speed to stimuli presented on the upper lip was dependent on the intensity of both T1 and T2. Increases in the intensity of T2 between 0.1 and 0.8 degrees C produced faster detection speeds. In general, as the intensity of T1 increased, the detection speed increased to identical T2 stimuli. The monkeys' T2-detection threshold was also dependent on the intensity of T1. 3. The psychophysical functions obtained from stimulation of the monkey's face were compared with those obtained from the volar surface of the monkey's forearm. Whereas the T2 thresholds obtained from stimulation of the monkey's forearm and face were similar, the psychophysical functions obtained from stimulation of the face were significantly steeper than those obtained from stimulation of the forearm. 4. The humans' detection speed of T2 stimuli presented on the face was monotonically related to the intensity of T2 and was dependent on the level of T1. The psychophysical functions obtained from the human's face were equivalent to those obtained from the monkey's faces. 5. A cross-modality matching procedure was used to examine the perceived intensity of pain sensation produced by T2 stimuli in human subjects. The magnitude estimates of these stimuli were dependent on the level of T1, as well as the intensity of T2. Detection speed, plotted as a function of the estimated magnitude of pain, independent of T1 and T2 temperature, was best fit by a logarithmic function.(ABSTRACT TRUNCATED AT 400 WORDS)     

Sympathetic activation during the cold pressor test: influence of stimulus area

The purpose of this study was to determine the effect of the size of the stimulus area on the muscle sympathetic nerve activity (MSNA), systolic arterial blood pressure (SAP), and heart rate responses to the cold pressor test. To accomplish this, these variables were measured before (control), during, and after 1.5 min of ice water immersion of either one or both hands in nine healthy subjects (aged 19-27 years). The cold stimulus elicited significant increases above control levels in all three variables under both conditions (P less than 0.05). Immersion of both hands produced a much greater increase in total MSNA (+366%) than immersion of a single hand (+187%) (P less than 0.05). However, the magnitudes of the increases in SAP and heart rate during two-hand immersion (29 +/- 6 mmHg and 10 +/- 2 beats min-1) were not significantly different from the responses during the one-hand trials (24 +/- 5 mmHg and 6 +/- 2 beats min-1, P greater than 0.05). There was a strong, direct relationship between total MSNA and SAP responses during one-hand immersion (r = 0.93, P less than 0.001) but not during immersion of both hands (r = 0.66, P = 0.08). These findings indicate that during the cold pressor test the magnitude of the increase in sympathetic discharge to skeletal muscle, but not the systolic blood pressure response, is influenced by the size of the tissue area exposed to the stimulus.     

Auditory enhancement of visual phosphene perception: The effect of temporal and spatial factors and of stimulus intensity

Multisensory integration of information from different sensory modalities is an essential component of perception. Neurophysiological studies have revealed that audiovisual interactions occur early in time and even within sensory cortical areas believed to be modality-specific. Here we investigated the effect of auditory stimuli on visual perception of phosphenes induced by transcranial magnetic stimulation (TMS) delivered to the occipital visual cortex. TMS applied at subthreshold intensity led to the perception of phosphenes when coupled with an auditory stimulus presented within close spatiotemporal congruency at the expected retinotopic location of the phosphene percept. The effect was maximal when the auditory stimulus preceded the occipital TMS pulse by 40 ms. Follow-up experiments confirmed a high degree of temporal and spatial specificity of this facilitatory effect. Furthermore, audiovisual facilitation was only present at subthreshold TMS intensity for the phosphenes, suggesting that suboptimal levels of excitability within unisensory cortices may be better suited for enhanced crossmodal interactions. Overall, our findings reveal early auditory–visual interactions due to the enhancement of visual cortical excitability by auditory stimuli. These interactions may reflect an underlying anatomical connectivity between unisensory cortices.     

The correlation of monkey medullary dorsal horn neuronal activity and the perceived intensity of noxious heat stimuli

1. We examined the relationship between the activity of medullary dorsal horn nociceptive neurons and the monkeys' ability to detect noxious heat stimuli. In two different detection tasks, the temperature of a contact thermode positioned on the monkey's face increased from 38 degrees C to temperatures between 44 and 48 degrees C (T1). After a variable time period, the thermode temperature increased an additional 0.2-1.5 degrees C (T2), and the monkeys' detection speed from the onset of T2 was determined. We previously have established that detection speed is a measure of the perceived intensity of noxious thermal stimuli. Nociceptive neurons were classified as wide-dynamic-range (WDR, responsive to innocuous mechanical stimuli with greater responses to noxious mechanical stimuli) and nociceptive-specific (NS, responsive only to noxious stimuli). WDR neurons were subclassified as WDR1 and WDR2 based on the higher slope values of the stimulus-response functions of WDR1 neurons. The monkeys were trained to detect small increases in noxious heat, and their detection speeds were correlated with the responses of WDR1, WDR2, and NS neurons. 2. Detection speeds to T2 temperatures of 1.0 degrees C from preceding T1 temperatures of 45 and 46 degrees C were faster during a preceding ascending series of stimuli than during a descending series. Similarly, the peak discharge frequencies of WDR1 neurons in response to the same stimuli were greater during the ascending series of T2 temperatures. In contrast, the responses of WDR2 and NS neurons showed no significant differences during the ascending and descending series of stimuli. 3. Detection speeds following 0.4, 0.6, and 0.8 degrees C T2 stimuli were higher when the preceding T1 temperature was 46 degrees C as compared with detection speeds to the identical stimuli when the preceding T1 temperature was 45 degrees C. WDR1 neurons also exhibited a significant increase in peak discharge frequency to these same T2 stimuli when the preceding T1 temperature was 46 degrees C. In contrast, the neuronal activity of WDR2 and NS neurons did not differ on 45 and 46 degrees C T1 trials. 4. The relationship between detection speed and neuronal peak discharge frequency was examined in response to different pairs of T1 and T2 stimuli when T1 was either 45 or 46 degrees C. There was a significant correlation between detection speed and neuronal discharge for WDR1 and WDR2 neurons. No correlation was observed for NS neurons. 5. The magnitude of neuronal activity on correctly detected and nondetected trials was compared when T1 was 46 degrees C and T2 was 0.2 degree C.(ABSTRACT TRUNCATED AT 400 WORDS)     

Chemesthesis and taste: evidence of independent processing of sensation intensity

The ability to perceive taste from temperature alone ("thermal taste") was recently shown to predict higher perceptual responsiveness to gustatory and olfactory stimuli. This relationship was hypothesized to be due in part to individual differences in CNS processes involved in flavor perception. Here we report three experiments that tested whether subjects who differ in responsiveness to thermal taste and/or chemical taste also differ in responsiveness to oral chemesthesis. In experiment 1, subjects identified as 'thermal tasters' (TTs) or 'thermal non-tasters' (TnTs) used the general Labeled Magnitude Scale to rate the intensity of sensations produced on the tongue tip by capsaicin, menthol, sucrose, NaCl, citric acid, and QSO4. TTs rated all four taste stimuli higher than did TnTs, whereas sensations of burning/stinging/pricking and temperature from capsaicin and menthol did not differ significantly between groups. In experiment 2, testing with capsaicin on both the front and back of the tongue confirmed there was no difference in ratings of burning/stinging/pricking when subjects were grouped according to the ability to perceive thermal taste. In experiment 3, subjects were classified as high- or low-tasters according to their ratings of sucrose sweetness rather than thermal taste. No group difference was found for perception of capsaicin even when presented in mixture with sucrose or NaCl. The results are discussed in the context of previous evidence of an association between chemesthesis and sensitivity to the bitter tastant PROP, and in terms of the various peripheral and central neural processes that may underlie intensity perception in taste and chemesthesis.     

Effect of static and dynamic heat pain stimulus profiles on the temporal dynamics and interdependence of pain qualities, intensity, and affect

Acute and chronic pains are characterized by a particular constellation of pain qualities, such as burning, aching, stinging, or sharp feelings. However, the temporal pattern of specific pain qualities and their relationship with pain and affect is not well understood. In addition, little is known about how the temperature time course of the stimulus impacts the temporal dynamics of pain qualities and the relationship between pain qualities. Therefore we applied two types of stimuli to the feet of 16 healthy subjects, each calibrated to evoke a similar pain magnitude (50/100): static stimulus held at constant intensity and dynamic stimulus increased in intensity in small steps. Stimulus runs consisted of three 30-s stimuli (either static or dynamic) with an interstimulus interval of 60 s. Continuous on-line ratings of pain, burning, sharp, stinging, cutting, and annoyance were obtained in separate runs, and the evoked responses were characterized by within-stimulus adaptation (early: 0- to 15-s peak vs. late: 25- to 40-s peak) and by their temporal properties (time to onset, peak, and end). The temporal profile of the burning sensation was similar to the pain and annoyance evoked by the static and dynamic stimuli. However, the sharp, stinging and cutting sensations attenuated in response to the static stimuli (P < 0.01) but intensified along with pain and affect in response to the dynamic stimuli (P < 0.05), whereas there was no attenuation in the evoked profiles of pain (P = 0.61), annoyance (P = 0.27), or burning quality (P = 0.27). These data demonstrate that specific pain qualities with known differences in underlying mechanisms have distinct temporal dynamics that depend on the stimulus intensity dynamics.     

The influence of incubatory photic stimuli on chicks' visual intensity preference for approach behavior.

Incubating chicks were presented with a high-intensity or low-intensity photic flicker stimulus, or with no photic stimulation. The chicks were tested at 16 hr posthatching for approach behavior, or at 96 hr for imprinting performance to the 2 visual flicker stimuli. The data were analyzed in accord with the arguments of whether those stimuli that effectively elicit approach behavior are determined by interaction between maturation and experience or by a genetic program. The results show that prehatch exposure to photic flicker stimuli affects initial approach behavior and imprinting performance, supporting the interaction position in opposition to the genetically programmed position.     

Dissociation of summation and peak latencies in visual processing: An MEG study on stimulus eccentricity

Research on the temporal characteristics of visual processing, as measured with critical flicker fusion or the latency of visual evoked potential (VEP), shows controversial results if different eccentricities of visual stimuli are compared. To clarify this question, a direct measure of cortical activity with magnetoencephalography (MEG) was applied to examine the neuronal summation latency and peak latency for both near and far peripheral stimuli. Consistent with cortical magnification, the peak amplitude for less eccentric stimuli was larger than that for more eccentric stimuli. More importantly, the current data also demonstrated longer cortical summation latency and peak latency for more eccentric visual stimuli, but only the summation latency difference between near and far stimuli correlated with the peak amplitude difference between near and far stimuli. These results suggest dissociable mechanisms of summation latency and peak latency with respect to their contributions to the stimulus eccentricity effect, and provide potential explanations for controversial results in previous studies.     

Sensation-seeking: electrodermal and behavioral effects of stimulus content and intensity

Although a number of studies support an arousal theory interpretation of differential sensation-seeking behavior, the conditions under which arousal correlates of this personality dimension are manifest is as yet unclear. Both theory and research suggest that among the external factors affecting the differential arousal response are stimulus relevance and stimulus intensity. The present study assessed the impact of these factors on both psychophysiological and behavioral responses. Subjects were preselected to represent the extremes of the sensation-seeking dimension, then exposed to auditory and visual presentations of a series of sexual and aggressive stimuli of systematically varied intensity. High sensation seekers gave larger amplitude SCRs to violent stimuli and larger initial responses to sexual stimuli presented visually, while verbal response intensities showed an opposite pattern. Overall, results provided support for an arousal theory interpretation of sensation-seeking, but suggested that the probability and magnitude of group differences is a somewhat complex function of stimulus intensity, stimulus modality, and perhaps other factors not yet assessed.