THRESHOLDS AND SUPRATHRESHOLD INTENSITY FUNCTIONS FOR CAPSAICIN IN OIL AND AQUEOUS BASED CARRIERS

Thresholds and responses to capsaicin in oil- and water-based model systems were compared. Thresholds were measured among 23 individuals using an ascending forced choice method of limits. Detection thresholds were 11.75 (± 1.31) mg/L in oil and 0.31 (± 0.03) mg/L in water. A horizontal labeled magnitude scale was used to obtain suprathreshold scaling functions in corn and soybean oils and in water systems using an emulsifier (polysorbate) or alcohol to solvate the capsaicin. In the water-based systems, capsaicin ranged from weak to very strong ratings over a range of 0.3 to 10 mg/L while the same perceptual range was achieved in oil over a range of 10 to 316 mg/L. Nonconsumers of hot/spicy foods generally had higher thresholds and higher suprathreshold responses in oil systems. Differences between user groups were less pronounced in water-based stimuli.     

Effect of the α2δ ligand, pregabalin, on colonic sensory and motor functions in healthy adults

Pregabalin, an α2δ ligand, is used clinically to treat somatic pain. A prior study suggested that pregabalin reduces distension-induced pain while increasing rectal compliance. We aimed to quantify effects of pregabalin on colonic sensory and motor functions and assess relationships between sensory effects and colonic compliance. We conducted a randomized, double-blind, placebo-controlled, parallel-group study of a single oral administration of 75 or 200 mg of pregabalin in 62 healthy adults (aged 18-75 yr). Subjects underwent left colon intubation. We assessed "stress-arousal symptoms", compliance, sensation thresholds, sensation ratings averaged over four levels of distension, fasting and postprandial colonic tone, and phasic motility index (MI). Analysis of covariance (adjusted for age, sex, body mass index, and corresponding predrug response) and proportional hazard models were used. There were no clinically important differences among treatment groups for demographics, predrug compliance, tone, MI, and sensation. Treatment was associated with reduced energy and increased drowsiness but no change in tension or relaxation. Sensation ratings averaged over the four distension levels were lower for gas sensation [overall effect P = 0.14, P = 0.05 (pregabalin 200 mg vs. placebo)] and for pain sensation [overall effect P = 0.12, P = 0.04 (pregabalin 200 mg vs. placebo)]. The magnitude of the effect of 200 mg of pregabalin relative to placebo is on average a 25% reduction of both gas and pain sensation ratings. Pregabalin did not significantly affect colonic compliance, sensation thresholds, colonic fasting tone, and MI. Thus 200 mg of pregabalin reduces gas and pain sensation and should be tested in patients with colonic pain.     

Affected by smells? Environmental chemical responsivity predicts odor perception

Strong negative reactions, physical symptoms, and behavioral disruptions due to environmental odors are common in the adult population. We investigated relationships among such environmental chemosensory responsivity (CR), personality traits, affective states, and odor perception. Study 1 showed that CR and neuroticism were positively correlated in a sample of young adults (n = 101), suggesting that persons high in neuroticism respond more negatively to environmental odors. Study 2 explored the relationships among CR, noise responsivity (NR), neuroticism, and odor perception (i.e., pleasantness and intensity) in a subset of participants (n = 40). High CR was associated with high NR. Regression analyses indicated that high CR predicted higher odor intensity ratings and low olfactory threshold (high sensitivity) predicted lower pleasantness ratings. However, neuroticism was not directly associated with odor ratings or thresholds. Overall, the results suggest that CR and odor thresholds predict perceptual ratings of odors and that high CR is associated with nonchemosensory affective traits.     

Test–retest reliability of subjective supra-threshold scaling of multiple pressure-pain sensations among healthy individuals: a study using hydraulic pressure algometry

Abstract

Background: Supra-threshold scaling of multiple pressure-pain sensations involves delivery of varied stimulus intensities, either via stimulus-dependent or response-dependent manner, and recording of subjective pain ratings by participants. The focus of this study was to determine the intra- and inter-session reliability of pain intensity and pain unpleasantness ratings related to pressure-pain thresholds (PPTs) of just noticeable pain (JNP), weak pain (WP) and moderate pain (MP) among healthy individuals.

Methods: Fourteen healthy participants (eight women, six men) participated in three sessions of testing at varied intervals over the course of 72?h. In session one, a multiple random staircase method using hydraulic pressure algometry was used to measure PPT of JNP, WP and MP on thumbnail bed. In session 2, ratings of pain intensity and pain unpleasantness were recorded when stimuli at levels corresponding to PPT of JNP, WP and MP were repeatedly applied before and after 20?min of no intervention.

Results: Interclass correlation coefficient (ICC) values for pain ratings of JNP, WP and MP in intra-session reliability were 0.810, 0.826 and 0.881, respectively, whereas the values were 0.817, 0.792 and 0.910, respectively, for inter-session reliability. ICC values for pain unpleasantness were also highly consistent and repeatable. Temporal summation of pain intensity and pain unpleasantness were not related to the repeated application of pressure stimuli.

Conclusions: The findings indicate that the pain intensity and pain unpleasantness ratings for stimuli at levels equal to the thresholds of JNP, WP and MP have good intra- and inter-session reliability.

Significance: This study showed that both pain intensity and pain unpleasantness of JNP, WP and MP have good intra- and inter-session reliability and agreement. Furthermore, the temporal summation of pain or unpleasantness is not related to repeated application of pressure stimuli.

Abbreviations: JNP: Just noticeable pain; WP: Weak pain; MP: Moderate pain; PPTs: pressure-pain thresholds; HPA: Hydraulic pressure algometry; MRSM: multiple random staircase method     

Spatial summation of heat pain in males and females

Sex differences in pain sensitivity have been found to vary between considerable and negligible. It has appeared that the pain stimulation method is critical in this context. It was assumed this might be due to the different degrees of spatial summation associated with the different pain stimulus modalities. Hence, sex differences were investigated in spatial summation of heat pain in 20 healthy women and 20 healthy men of similar age. Pain thresholds were assessed by a tracking procedure and responses to supra-threshold pain stimulation by numerical ratings. Heat stimuli were administered by a thermode with contact areas of 1, 3, 6 and 10 cm2. Pain thresholds were significantly higher with smaller areas stimulated than with larger ones. No significant effect of area was found for the ratings of the supra-threshold stimuli, the intensities of which were tailored to the individual pain threshold. Consequently, spatial summation of heat pain appeared to result mainly in a shift of the pain threshold on the ordinate and not a change of slope of the stimulus-response function in the pain range. In neither of the two pain parameters were there any sex differences. Therefore, the present study demonstrated that sex differences in spatial summation of heat pain are unlikely.     

A comparison of different methods used to assess sensitivity to the taste of phenylthiocarbamide (PTC)

Four methods for assessing sensitivity to the bitterness ofphenylthiocarbamide (PTC) and propylthiouracil (PROP) were compared.Good agreement was found among results from forcedchoice detectionthresholds, recognition thresholds, and category ratings ofsingle stimuli. Testing by means of papers impregnated withthese compounds led to a high incidence of false positive responsesfrom insensitive subjects. Phenylthiocarbamide was a slightlybetter discriminator of sensitive from insensitive subjectsthan was propythiouracil. Category ratings of the intensityof the antimodal PTC threshold concentration are a valid, reliableand efficient screening method. Relative safety in the use ofPTC and PROP is discussed.     

Effect of sex on perception of rectosigmoid stimuli in irritable bowel syndrome

In irritable bowel syndrome (IBS) patients, the relationship between sex and sensitivity to visceral stimuli is incompletely understood. Our aim was to evaluate the effect of sex on perceptual responses to visceral stimulation in IBS. Fifty-eight IBS patients (mean age 42+/-1 yr; 34 men, 24 women) and 26 healthy controls (mean age 38+/-3 yr; 9 men, 17 women) underwent barostat-assisted distensions of the rectum and sigmoid colon. Rectal discomfort thresholds were measured using a randomized, phasic distension paradigm before and after repeated noxious sigmoid stimulation (SIG, 60-mmHg pulses). Sex had a significant effect on rectal discomfort thresholds. Women with IBS were the most sensitive (lower thresholds [27+/-2.7 mmHg] and higher ratings), with significantly lower rectal discomfort thresholds compared with men with IBS (38+/-2.3 mmHg) and healthy women who were the least sensitive (41.9+/-3.2 mmHg; both P<0.01). There were no significant differences in rectal discomfort thresholds between healthy men (34+/-4.3 mmHg) and men with IBS. Across both IBS and control groups, women demonstrated a significant lowering of discomfort thresholds after noxious sigmoid stimulation (P<0.01), while men did not. Sex significantly influences perceptual sensitivity to rectosigmoid distension. Women show greater perceptual responses to this paradigm.     

Effects of linoleic acid on sweet, sour, salty, and bitter taste thresholds and intensity ratings of adults

Evidence supporting a taste component for dietary fat has prompted study of plausible transduction mechanisms. One hypothesizes that long-chain, unsaturated fatty acids block selected delayed-rectifying potassium channels, resulting in a sensitization of taste receptor cells to stimulation by other taste compounds. This was tested in 17 male and 17 female adult (mean +/- SE age = 23.4 +/- 0.7 yr) propylthiouracil tasters with normal resting triglyceride concentrations (87.3 +/- 5.6 mg/day) and body mass index (23.3 +/- 0.4 kg/m(2)). Participants were tested during two approximately 30-min test sessions per week for 8 wk. Eight stimuli were assessed in duplicate via an ascending, three-alternative, forced-choice procedure. Qualities were randomized over weeks. Stimuli were presented as room-temperature, 5-ml portions. They included 1% solutions of linoleic acid with added sodium chloride (salty), sucrose (sweet), citric acid (sour), and caffeine (bitter) as well as solutions of these taste compounds alone. Participants also rated the intensity of the five strongest concentrations using the general labeled magnitude scale. The suprathreshold samples were presented in random order with a rinse between each. Subjects made the ratings self-paced while wearing nose clips. It was hypothesized that taste thresholds would be lower and absolute intensity ratings or slopes of intensity functions would be higher for the stimuli mixed with the linoleic acid. Thresholds were compared by paired t-tests and intensity ratings by repeated measures analysis of variance. Thresholds were significantly higher (i.e., lower sensitivity) for the sodium chloride, citric acid, and caffeine solutions with added fatty acid. Sweet, sour, and salty intensity ratings were lower or unchanged by the addition of a fatty acid. The two highest concentrations of caffeine were rated as weaker in the presence of linoleic acid. These data do not support a mechanism for detecting dietary fats whereby fatty acids sensitize taste receptor cells to stimulation by taste compounds.     

Effects of the opioid remifentanil on olfactory function in healthy volunteers.

The effects of opioids on human subjective olfactory function have rarely been investigated. This is despite the fact that opioid receptors are widely distributed throughout the olfactory systems. Using an established validated test of subjective olfactory function, olfactory threshold, odor discrimination and odor identification performance were tested in 16 healthy volunteers before opioid administration and at steady state after 3 hours remifentanil infusion. Each one man and one women were assigned randomly to one out of eight predefined remifentanil target plasma concentrations: 0, 1.2, 1.8, 2.4, 3, 3.6, 4.8, and 6 ng/ml. In the thirteen subjects that had completed the tests, olfactory thresholds were elevated with increasing remifentanil dose, and this correlated statistically significant with the remifentanil dose. Remifentanil plasma concentrations were linearly related to changes in olfactory thresholds. In contrast, effects of remifentanil on odor discrimination and identification were not statistically significant. However, remifentanil target plasma concentrations were also significantly correlated with the subjects' ratings of tiredness and drowsiness, although only drowsiness was significantly correlated with the differences in odor thresholds. We conclude that opioid administration leads to impaired olfactory function expressed in raised olfactory thresholds. This is compatible with previously reported opioidergic effects at the level of the olfactory bulb.     

Further contributions to the mathematical biophysics of visual aesthetics

In previous papers cases were considered in which a visual pattern consists of a relatively small number of relatively strongly excited elements. Those cases are of interest in the theory of visual perception and aesthetic rating of artificial man made patterns. By an extension of the theory so as to take into account the finite thresholds of the inhibiting fibers a theory of aesthetic ratings of pattern consisting of a very large number of elements is outlined. This type of theory is applicable to natural patterns, such as landscapes.     

The Scent of Blood: A Driver of Human Behavior?

The scent of blood is potentially one of the most fundamental and survival-relevant olfactory cues in humans. This experiment tests the first human parameters of perceptual threshold and emotional ratings in men and women of an artificially simulated smell of fresh blood in contact with the skin. We hypothesize that this scent of blood, with its association with injury, danger, death, and nutrition will be a critical cue activating fundamental motivational systems relating to either predatory approach behavior or prey-like withdrawal behavior, or both. The results show that perceptual thresholds are unimodally distributed for both sexes, with women being more sensitive. Furthermore, both women and men’s emotional responses to simulated blood scent divide strongly into positive and negative valence ratings, with negative ratings in women having a strong arousal component. For women, this split is related to the phase of their menstrual cycle and oral contraception (OC). Future research will investigate whether this split in both genders is context-dependent or trait-like.     

Augmented Pain Processing in Primary and Secondary Somatosensory Cortex in Fibromyalgia: A Magnetoencephalography Study Using Intra-Epidermal Electrical Stimulation

The aim of this study was to investigate augmented pain processing in the cortical somatosensory system in patients with fibromyalgia (FM). Cortical evoked responses were recorded in FM (n = 19) and healthy subjects (n = 21) using magnetoencephalography after noxious intra-epidermal electrical stimulation (IES) of the hand dorsum (pain rating 6 on a numeric rating scale, perceptually-equivalent). In addition, healthy subjects were stimulated using the amplitude corresponding to the average stimulus intensity rated 6 in patients with FM (intensity-equivalent). Quantitative sensory testing was performed on the hand dorsum or thenar muscle (neutral site) and over the trapezius muscle (tender point), using IES (thresholds, ratings, temporal summation of pain, stimulus-response curve) and mechanical stimuli (threshold, ratings). Increased amplitude of cortical responses was found in patients with FM as compared to healthy subjects. These included the contralateral primary (S1) and bilateral secondary somatosensory cortices (S2) in response to intensity-equivalent stimuli and the contralateral S1 and S2 in response to perceptually-equivalent stimuli. The amplitude of the contralateral S2 response in patients with FM was positively correlated with average pain intensity over the last week. Quantitative sensory testing results showed that patients with FM were more sensitive to painful IES as well as to mechanical stimulation, regardless of whether the stimulation site was the hand or the trapezius muscle. Interestingly, the slope of the stimulus-response relationship as well as temporal summation of pain in response to IES was not different between groups. Together, these results suggest that the observed pain augmentation in response to IES in patients with FM could be due to sensitization or disinhibition of the cortical somatosensory system. Since the S2 has been shown to play a role in higher-order functions, further studies are needed to clarify the role of augmented S2 response in clinical characteristics of FM.     

Sex differences in nociceptive withdrawal reflex and pain perception

Experimentally induced pain often reveals sex differences, with higher pain sensitivity in females. The degree of differences has been shown to depend on the stimulation and assessment methods. Since sex differences in pain develop anywhere along the physiological and psychological components of the nociceptive system, we intended to compare the nociceptive flexion reflex (NFR) as a more physiological (spinal) aspect of pain procession to the verbal pain report of intensity and unpleasantness as the more psychological (cortical) aspect. Twenty female and twenty male healthy university students were investigated by use of nociceptive flexion reflex threshold (staircase method) after electrical stimulation of the N. suralis. Furthermore, we assessed supra-threshold reflex responses (latency, amplitude and area) by applying 10 stimuli 5 mA above reflex threshold. Following each stimulation, the subjects provided pain ratings of intensity and unpleasantness on a visual analogue scale. Females exhibited marked lower nociceptive flexion reflex thresholds than males, while the supra-threshold reflex response tailored to the individual reflex threshold did not show any significant differences. The verbal pain ratings, corrected for NFR threshold, were not found to differ significantly. The large sex differences in nociception that were present in NFR threshold but not in the pain ratings corroborate the hypothesis that spinal processes contribute substantially to sex differences in pain procession.     

Summation of perceptual cues in natural visual scenes

Natural visual scenes are rich in information, and any neural system analysing them must piece together the many messages from large arrays of diverse feature detectors. It is known how threshold detection of compound visual stimuli (sinusoidal gratings) is determined by their components' thresholds. We investigate whether similar combination rules apply to the perception of the complex and suprathreshold visual elements in naturalistic visual images. Observers gave magnitude estimations (ratings) of the perceived differences between pairs of images made from photographs of natural scenes. Images in some pairs differed along one stimulus dimension such as object colour, location, size or blur. But, for other image pairs, there were composite differences along two dimensions (e.g. both colour and object-location might change). We examined whether the ratings for such composite pairs could be predicted from the two ratings for the respective pairs in which only one stimulus dimension had changed. We found a pooling relationship similar to that proposed for simple stimuli: Minkowski summation with exponent 2.84 yielded the best predictive power (r=0.96), an exponent similar to that generally reported for compound grating detection. This suggests that theories based on detecting simple stimuli can encompass visual processing of complex, suprathreshold stimuli.     

Changes in pain perception and hormones pre- and post-kumdo competition

The psychological stress of competition is a powerful stimulus affecting numerous hormones, which in turn change how pain is perceived. This study investigated whether a kumdo (kendo) team competition may be related to changes in hormones and pain. Seventeen healthy male kumdo practitioners participated in this experiment. Pain experiments were conducted by applying noxious stimuli with a thermal stimulator 10 min before a kumdo competition and 30 min post-competition. Serum testosterone, cortisol, beta-endorphin levels, pain thresholds, pain ratings at 48 °C and during blood sampling (sampling pain), anxiety, blood pressure, and heart rate were measured pre- and post-competition. Anxiety, pain threshold, testosterone/cortisol ratio, and blood pressure were significantly higher pre-competition compared to post-competition, while cortisol and pain ratings were significantly lower pre-competition than post-competition. There were significant correlations between the number of previous competitions and testosterone levels both pre-competition and post-competition. In pre-competition measurements, sampling pain increased with an increase in systolic blood pressure, heart rate, and beta-endorphins, and a decrease in age. In post-competition measurements, sampling pain increased with an increase in diastolic blood pressure and a decrease in testosterone levels. These results indicate that severe psychological pre-competition stress was associated with reduced pain ratings, perhaps in order to improve athletic performance. This also suggests that competitors may be at risk of potential injury due to changes in pain perception, and careful consideration should be taken to avoid potential injury before and during competition.     

Differential spatial displacement discrimination with interfering stimuli

Differential spatial displacement discrimination thresholds were determined for a configuration of three blobs with Gaussian spatial and temporal contrast envelopes. This task is similar to the well known three-dot alignment hyperacuity task. Thresholds determined in the presence of interfering stimuli were identical to thresholds determined without these flanking stimuli. The thresholds scale linearly with stimulus size over at least two decades. We conclude that (i) the mechanisms that compute differential spatial displacement for the three-blob alignment task are not disturbed by the presence of neighbouring stimuli, even when these enter the region over which the computations are performed and (ii) at all levels of resolution similar mechanisms are used to compute differential spatial displacement.     

Thresholds for the perception of hand-transmitted vibration: dependence on contact area and contact location

The detection of vibration applied to the glabrous skin of the hand varies with contact conditions. Three experiments have been conducted to relate variations in the perception of hand-transmitted vibration to previously reported properties of tactile channels. The effects of a surround around the area of contact, the size of the area of contact, the location of the area of contact, the contact force, and the hand posture on perception of thresholds were determined for 8-500 Hz vibration. Removal of a surround around a contact area on the fingertip elevated thresholds of the NP II channel (FA I fibres) at frequencies less than 31.5 Hz and reduced thresholds of the Pacinian channel (FA II fibres) at frequencies greater than about 63 Hz. When no surround was present, thresholds reduced systematically as the contact area increased from the fingertip to the whole hand at frequencies from 16 to 125 Hz, although the decrease was not inversely proportional to the increase in contact area. The results are partly explained by spatial summation in the Pacinian channel (FA II fibres) and the involvement of the NP II channel (SA II) with some influence of biodynamic responses and contact pressures. There were regional differences in sensitivity over the hand within the NP I channel but not within the Pacinian channel: the NP I thresholds (less than 31.5 Hz) decreased from proximal to distal regions of the hand, whereas the Pacinian thresholds (125 Hz) were independent of contact location over the hand.     

Quantitative Studies of Stimulus Coding in First-Order Vibrissa Afferents of Rats. 1. Receptive Field Properties and Threshold Distributions

We examined stimulus-response relationships of vibrissa-activated mechanosensory neurons of the rat's fifth (trigeminal) ganglion. Single-unit activity was recorded with tungsten microelectrodes. The vibrissae were deflected with a variety of parametrically controlled stimulus waveforms.

We found that the receptive field of each vibrissa-activated neuron consisted of a single vibrissa. Few, if any, unambiguous examples of spontaneous activity were observed in these neurons. Even if true spontaneous activity was present, its observed incidence was low, as were the measured discharge rates.

Thresholds of individual neurons were usually quite discrete; often a 1-2% increase in pulse magnitude (angular displacement) above a level to which the neuron did not respond caused it to discharge on every trial. The distribution of thresholds for the sample was continuous with a median of about 1° and a range of over three orders of magnitude. The most sensitive neurons responded to deflections of less than 0.1°. Many neurons responded to a single suprathreshold pulse with more than one spike. We found no consistent relationships among the thresholds of the additional evoked discharges of an individual neuron other than that the total number of evoked spikes either increased or stayed the same, but never decreased, as stimulus magnitude increased.

About one-third of the neurons examined had velocity thresholds below 3°/sec. Above that value, thresholds were distributed continuously throughout a range of over three orders of magnitude. The median velocity threshold was about 100°/sec. The broad and continuous distributions of both magnitude and velocity thresholds suggest that a population of vibrissa-activated neurons can code stimulus strength smoothly and continuously over a wide range, even though individual neurons may be poorly suited to do so.