Adaptive modifications of cold pain (author's transl)]

38 healthy subjects 22-28 years of age underwent the cold-pressor-test seven times on each of 21 consecutive days always at the same time of day. The subjective sensations of cold pain and the objective circulatory reactions were registered. There was observed only a very distinct subjective cold pain habituation from one exposition to the other. The habituation effect on blood pressure reaction however was of expected extent. The long term adaptation showed to have effect on the predominance of the two components of pain perception the epicritic and protopathic pain experience. Initially the cold stimulus produced an overwhelmingly protopathic sufferenig whilst at the end of the three weeks of adaptation there remained only a reduced and localized epicritic pain sensation. Typological differences of pain reactions and pain adaptation are discussed.     

Cold habituation does not improve manual dexterity during rest and exercise in 5 °C

When exposed to a cold environment, a barehanded person experiences pain, cold sensation, and reduced manual dexterity. Both acute (e.g. exercise) and chronic (e.g. cold acclimatization or habituation) processes might lessen these negative effects. The purpose of this experiment was to determine the effect of cold habituation on physiology, perception, and manual dexterity during rest, exercise, and recovery in 5 °C. Six cold weather athletes (CWA) and eight non habituated men (NON) volunteered to participate in a repeated measures cross-over design. The protocol was conducted in 5 °C and was 90 min of resting cold exposure, 30 min of cycle ergometry exercise (50 % VO_{2 peak}), and 60 min of seated recovery. Core and finger skin temperature, metabolic rate, Purdue Pegboard dexterity performance, hand pain, thermal sensation, and mood were quantified. Exercise-induced finger rewarming (EIFRW) was calculated for each hand. During 90 min of resting exposure to 5 °C, the CWA had a smaller reduction in finger temperature, a lower metabolic rate, less hand pain, and less negative mood. Despite this cold habituation, dexterity performance was not different between groups. In response to cycle ergometry, EIFRW was greater in CWA (~12 versus 7 °C) and occurred at lower core temperatures (37.02 versus 37.31 °C) relative to NON but dexterity was not greater during post-exercise recovery. The current data indicate that cold habituated men (i.e., CWA) do not perform better on the Purdue Pegboard during acute cold exposure. Furthermore, despite augmented EIFRW in CWA, dexterity during post-exercise recovery was similar between groups.     

Rubber Hand Illusion Reduces Discomfort Caused by Cold Stimulus

There is a growing interest in body-ownership disruptions and their consequences for subjective experiences such as tactile sensations or pain. Here, we investigated the effect of the rubber hand illusion (RHI) on the perceived discomfort caused by cold stimulus applied to the real hand. The results showed reduced discomfort to cold reflected in behavioural and subjective measures. The stronger the illusion, the later the cold temperature became unpleasant and the less intense the experience was rated. We discuss the link between thermoception and body ownership as well as possible theoretical and methodological implications for studies on pain experience under RHI.     

Adjustment of the peripheral circulation in human cold acclimatization: A critical review

The literature concerning the peripheral circulatory changes in human cold acclimatization is briefly reviewed. The warmer extremities in the cold earlier attributed to a “Metabolic acclimatization to cold” are possibly an effect of improved physical fitness, but the underlying mechanisms are still unclear. The evidence concerning a total body acclimatization to cold is equivocal. An increased hand vasoconstriction in the cold in subjects with an insulative type of acclimatization to cold may be of relatively little importance for the general thermal balance and accentuate the deteriorating effect of cold on hand functioning. There is good evidence for local manifestations of a cold acclimatization in Man: a quickened onset of an increased cold induced vasodilatation, markedly reduced or abolished cold pain and a lowered cold pressor response. The underlying mechanism is most probably a central nervous habituation to cold—possibly the main physiological mechanism in human cold acclimatization. The importance of an intact hand functioning for survival in the cold is stressed.     

Human cold air habituation is independent of thyroxine and thyrotropin.

Thyroxine (T4) is required in species possessing brown adipose tissue (BAT) for the maintenance of cold tolerance and adaptation. In humans, who possess negligible quantities of BAT, the importance of T4 has not been demonstrated. We studied the effects of decreased serum T4 and thyrotropin (TSH) on human cold habituation after repeated cold air exposures. Eight men (T3+) received a single daily dose of triiodothyronine (T3; 30 micrograms/day), and another eight men (T3-) received a placebo. All 16 normal thyroid men underwent a standardized cold air test (SCAT) under basal conditions in January and again in March after eighty 30-min 4.4 degrees C air exposures (10/wk). Measurements of basal metabolic rate (BMR), O2 consumption (VO2), mean arterial pressure (MAP), plasma norepinephrine (NE), serum TSH, free and total T4, and free and total T3 were repeated before and after 8 wk of exposure. TSH, free T4, and total T4 were 50% lower for T3+ than for T3- subjects. Total and free T3 were not different between groups. BMR was unchanged after habituation, whereas the cold-stimulated VO2, MAP, and NE were significantly reduced for all subjects in March. The relationship between VO2 and NE (r2 = 0.44, P less than 0.001) during the initial SCAT was unchanged with habituation. We suggest that human cold habituation is independent of major changes in circulating T4 and TSH.     

Neural Correlates of Empathy with Pain Show Habituation Effects. An fMRI Study

Background

Neuroimaging studies have demonstrated that the actual experience of pain and the perception of another person in pain share common neural substrates, including the bilateral anterior insular cortex and the anterior midcingulate cortex. As many fMRI studies include the exposure of participants to repeated, similar stimuli, we examined whether empathic neural responses were affected by habituation and whether the participants'' prior pain experience influenced these habituation effects.

Method

In 128 trials (four runs), 62 participants (31 women, 23.0 ± 4.2 years) were shown pictures of hands exposed to painful pressure (pain pictures) and unexposed (neutral pictures). After each trial, the participants rated the pain of the model. Prior to the experiment, participants were either exposed to the same pain stimulus (pain exposure group) or not (touch exposure group). In order to assess possible habituation effects, linear changes in the strength of the BOLD response to the pain pictures (relative to the neutral pictures) and in the ratings of the model’s pain were evaluated across the four runs.

Results

Although the ratings of the model’s pain remained constant over time, we found neural habituation in the bilateral anterior/midinsular cortex, the posterior midcingulate extending to dorsal posterior cingulate cortex, the supplementary motor area, the cerebellum, the right inferior parietal lobule, and the left superior frontal gyrus, stretching to the pregenual anterior cingulate cortex. The participant’s prior pain experience did neither affect their ratings of the model’s pain nor their maintenance of BOLD activity in areas associated with empathy. Interestingly, participants with high trait personal distress and fantasy tended to show less habituation in the anterior insula.

Conclusion

Neural structures showed a decrease of the BOLD signal, indicating habituation over the course of 45 minutes. This can be interpreted as a neuronal mechanism responding to the repeated exposure to pain depictions, which may be regarded as functional in a range of contexts.     

Responsiveness to sucrose and habituation of the proboscis extension response in honey bees

In honey bees, complex behaviours such as associative learning correlate with responsiveness to sucrose. In these behaviours, the subjective evaluation of a sucrose stimulus influences the behavioural performance. Habituation is a well-known form of non-associative learning. In bees, the proboscis extension response can be habituated by repeatedly stimulating the antennae with a low sucrose concentration. A high sucrose concentration can dishabituate the response. This study tests whether habituation correlates with responsiveness to sucrose in bees of different behavioural states and in bees which are habituated with different sucrose concentrations. Habituation and dishabituation in newly emerged bees, 5-day-old bees and foragers strongly correlated with responsiveness to sucrose. Bees with high responsiveness to sucrose displayed a lower degree of habituation and showed greater dishabituation than bees with low responsiveness. The degree of habituation and dishabituation also depended on the concentration of the habituation stimulus. These experiments demonstrate for the first time in a non-associative learning paradigm that the subjective strength of a sucrose stimulus determines the behavioural performance. Non-associative learning shares this property with associative learning, which suggests that the two processes might rely on similar neural mechanisms.Abbreviations: GRS Gustatory response score - PER Proboscis extension response     

Heart-rate reactivity to cold pressor stress following biofeedback training

Three previous studies have shown that biofeedback training is useful in modifying heart-rate and pain ratings during ice water stimulation (cold pressor test). Subjects were given an initial cold pressor followed by heart-rate biofeedback training and a final cold pressor test in which they were instructed to control their heart rate in accordance with the prior training. It was assumed that a heart-rate control skill had been learned. In the present study, two groups of subjects (N = 9 each) were given either increase or decrease heart-rate biofeedback training following the same procedures as previously, but subjects were not instructed to control their heart rate during the final cold pressor test. Heart rate, skin conductance, electromyographic activity, and respiration were measured. The biofeedback training effects replicate the previous results. However, no heart-rate or pain rating differences were found between the two groups during the final cold pressor test. Thus, previous findings cannot be accounted for simply by a shift in heart rate and/or pain reactivity following training itself. The findings suggest that a biofeedback strategy may be useful in modifying physiological and subjective responses to painful stimuli but only if it can be used as an active coping skill.     

Individual and Gender Differences in Subjective and Objective Indices of Pain: Gender,Fear of Pain,Pain Catastrophizing and Cardiovascular Reactivity

According to fear-avoidance models of pain perception, heightened fear of pain may increase disruptive effects of pain; however, the extent to which this affects self-reported pain severity versus physiological indices of pain is not well delineated. The current study examined self-report measures and physiological indices of pain during a cold pressor (CP) task. Individual differences in fear of pain and pain catastrophizing were also assessed via questionnaire. The primary aim of the current study was to examine the extent to which individual differences associated with fear and catastrophizing in response to pain influences subjective and physiological measures of pain. A secondary aim was to examine gender differences associated with response to pain. Average subjective pain ratings were higher for females than males. In contrast, males exhibited higher systolic and diastolic reactivity in response to the CP task relative to females, as well as failure to fully recover to baseline levels. Follow-up correlational analyses revealed that subjective pain ratings were positively associated with fear of pain in both sexes, but were not associated with cardiovascular indices. These results suggest that fear of pain and pain catastrophizing do not influence cardiovascular responses to induced pain. Further research is necessary in order to determine whether these gender differences in blood pressure and heart rate response profiles are due to biological or psychosocial influences. Results support the notion that fear of pain increases subjective pain ratings, but does not influence cardiovascular responses during CP pain-induction.     

Effect of cold pressor test on visual reaction time and auditory reaction time

Influence of stress (cold) on visual reaction time (VRT) for red, green and yellow colours and auditory reaction time (ART) for high and low pitched sounds was studied in 60 healthy subjects (17-19 years) by digital display response time apparatus.Pain threshold and pain tolerance time were 23.02 +/- 8.11 and 249.35 +/- 64.88 sec. respectively. During the standard cold pressor test (CPT), there was significant increase (P < 0.01) in VRT for all the three colours, the increase being the least for the red colour. There was significant increase (P < 0.01) in ART for both high and low pitched sounds.There was increase in heart rate and respiratory rate as compared to controls. This increase in VRT and ART with CPT was probably due to decreased conduction velocity of nerves, which could be due to vasoconstriction attributed to increased sympathetic activity caused by cold and pain.     

Reproducibility of human brain activity evoked by esophageal stimulation using functional magnetic resonance imaging

Functional MRI is a popular tool for investigating central processing of visceral pain in healthy and clinical populations. Despite this, the reproducibility of the neural correlates of visceral sensation by use of functional MRI remains unclear. The aim of the present study was to address this issue. Seven healthy right-handed volunteers participated in the study. Blood oxygen level-dependent contrast images were acquired at 1.5 T while subjects received nonpainful and painful phasic balloon distensions ("on-off" block design, 10 stimuli per "on" period, 0.3 Hz) to the distal esophagus. This procedure was repeated on two further occasions to investigate reproducibility. Painful stimulation resulted in highly reproducible activation over three scanning sessions in the anterior insula, primary somatosensory cortex, and anterior cingulate cortex. A significant decrease in strength of activation occurred from session 1 to session 3 in the anterior cingulate cortex, primary somatosensory cortex, and supplementary motor cortex, which may be explained by an analogous decrease in pain ratings. Nonpainful stimulation activated similar brain regions to painful stimulation, but with greater variability in signal strength and regions of activation between scans. Painful stimulation of the esophagus produces robust activation in many brain regions. A decrease in subjective perception of pain and brain activity from the first to the final scan suggests that serial brain imaging studies may be affected by habituation. These findings indicate that for brain imaging studies that require serial scanning, development of experimental paradigms that control for the effect of habituation is necessary.     

Habituation of thermal sensations, skin temperatures, and norepinephrine in men exposed to cold air.

We studied habituation processes by exposing six healthy men to cold air (2 h in a 10 degrees C room) daily for 11 days. During the repeated cold exposures, the general cold sensations and those of hand and foot became habituated so that they were already significantly less intense after the first exposure and remained habituated to the end of the experiment. The decreases in skin temperatures and increases in systolic blood pressure became habituated after four to six exposures, but their habituations occurred only at a few time points during the 120-min cold exposure and vanished by the end of the exposures. Serum thyroid-stimulating hormone, total thyroxine and triiodothyronine, norepinephrine, epinephrine, cortisol, and total proteins were measured before and after the 120-min cold exposure on days 0, 5, and 10. The increase in norepinephrine response became reduced on days 5 and 10 and that of proteins on day 10, suggesting that the sympathetic nervous system became habituated and hemoconcentration became attenuated. Thus repeated cold-air exposures lead to habituations of cold sensation and norepinephrine response and to attenuation of hemoconcentration, which provide certain benefits to those humans who have to stay and work in cold environments.     

Habituation of the cold pressor response in normo- and hypertensive human subjects

The changes in cardiovascular response to repeated cold-pressor test were studied in young normotensive and in young hypertensive subjects. The cold stimulus consisted of immersing one foot in cold water (4 degrees C) for 60 s. Non-invasive methods were used to record the cardiovascular responses: blood flow of the calf was measured using venous occlusion plethysmography, arterial blood pressure with sphygmomanometery, heart rate with electrocardiography. The vascular conductance level in the calf was higher in hypertensive subjects than in normotensives. The difference remained throughout the series of 6 daily experiments. In both hypertensive and normotensive groups of subjects some individuals responded to the cold stimulus with vasodilatation in the calf muscles, others with vasoconstriction. In the hypertensives blood flow increased more and habituation was only transient with a strong tendency for the vasodilatory response to recover, while in normotensives habituation was rapid and complete. Vasoconstrictor responses showed no signs of reduction. The blood pressure increases were larger in hypertensives and remained unaltered within the period of repeated tests (6 days). There was not significant difference between the heart rate changes in the two groups of subjects. It is concluded that the vasculature of the calf shows lower tone and is more labile during the early stage of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)     

Temperature dependent plasticity of habituation in the crayfish

To determine the effects of thermal preconditioning on a simple form of learning and memory, habituation, we preconditioned crayfish with extreme temperatures and subsequently analysed their effects on mechanosensory input that evokes a response in the lateral giant interneurons, within the normal temperature range of the animal. We found that repetitive stimulation with a 1 s interstimulus interval led to habituation of the response the lateral giant in control animals at 22°C. Neither heat nor cold preconditioning had any effect on the probability of evoking a response in the lateral giant nor on the rate at which habituation occurred. With a 1 min interstimulus interval, however, the rate of habituation of the lateral giant in the heat-preconditioned group was less than either the control or cold-preconditioned animals. The effect of heat or cold pre-exposure was specific to the input to the lateral giant at control temperatures. For example, at 22°C prior heat and cold preconditioning had no effect on spontaneous reductor motor neurone activity. They did, however, provide thermoprotection at extreme temperatures, with the probability of spontaneous activity higher in the cold-preconditioned group at low temperatures but higher in the heat-preconditioned group at higher temperatures.     

Gender differences in predator induced pain perception in rats

Pain is an unpleasant sensation. It warns the living being about the impending damage to the tissues. The perception of pain is influenced by physical and psychological factors. The impact of chronic intermittent psychological stress on pain perception and the differences in antinociceptive responses have been studied in male and anestrous female albino rats. Fifteen rats in each group were subjected to psychological stress, by exposing them to their natural predator--cat, for a duration of 20 min daily for 12 consecutive days. Tail flick response latency to radiant heat was used as a measure to evaluate pain perception. It was observed that both the groups had a relatively high pain threshold at the beginning of exposure schedule due to the modulation of opioid analgesic system by the higher level of circulating testosterone in males and low level of estrogen in anaestrous females. However, the threshold for pain perception showed a gradually declining trend in both the groups over the next 11 days to reach the control values. This increase in sensitivity to pain or decreased pain threshold could be attributed to the phenomenon of habituation.     

Segmental inhibition of laser-evoked brain potentials by ipsi- and contralaterally applied cold pressor pain.

An experiment was designed to quantify the inhibitory effect of cold pressor pain (ice water immersion) on brain potentials evoked by acute laser-induced pain. One hand (including the C7 dermatome) was immersed into ice water and simultaneously the laser-evoked brain potentials were elicited consecutively from the right and left lower forearms within the C7 dermatomes. The cold pressor pain was continuously rated on a visual analogue scale (VAS). The size of the averaged brain potentials evoked from the ipsi- and contralateral C7 dermatomes were reduced significantly during cold pressor pain. The largest decrease was obtained for the potentials evoked within the C7 dermatome ipsilateral to the cold pressor pain. The size (power) of the brain potentials to individual stimuli could be measured and was correlated to the intensity of the cold pressor pain (VAS score). During the onset phase of cold pressor pain, there was a decrease in power of the individual brain potentials evoked from the C7 dermatome contralateral to the cold pressor pain but the potentials, evoked from the C7 dermatome ipsilateral to cold pressor pain, were decreased more. The overall rating of the laser-induced pain intensity showed that the perceived intensity was lowest when evoked from the dermatome concurrently exposed to cold pressor pain.     

Decrease in excitability of LG following habituation of the crayfish escape reaction

Crayfish escapes from threatening stimuli to the abdomen by tailflipping upwards and forwards. This lateral giant (LG)-mediated escape reaction habituates readily upon repetitive sensory stimulation. Using an isolated abdominal nerve cord preparation, we have analyzed the change in LG activity by applying additional sensory stimulation after different periods following habituation to characterize the retention of LG habituation. Results show that the LG mediated response habituates more quickly, but the retention time is shorter, as repetitive sensory stimulation is applied at progressively shorter inter-stimulus time intervals. The spike response of LG recovers quickly, within several minutes after habituation, but they fail to spike when an additional stimulus is applied after specific long periods following habituation. The critical period of the delay for this decrease in excitability of LG is dependent on the inter-stimulus time interval of the initial repetitive stimulus. As the inter-stimulus interval became longer, the delay needed for decrease in excitability became shorter. Furthermore, the local injection of 10^–6 mol l^–1 octopamine into the neuropil just following habituation promotes the achievement of decrease in excitability. No effects were observed when 10^–6 mol l^–1 serotonin and tyramine were injected. These results suggested octopamine promotes decrease in excitability of LG following habituation.     

Estimation of the initial velocity of enzyme-catalysed reactions by non-linear regression analysis of progress curves.

Most methods for studying the kinetic properties of an enzyme involve the determination of initial velocities. When the reaction progress curve shows significant curvature due to depletion of the substrate, accumulation of inhibitory products or instability of the enzyme, estimation of the initial velocity is a subjective and inexact process. Two methods have been suggested [Cornish-Bowden (1975) Biochem. J. 144, 305-312; Boeker (1982) Biochem J. 203, 117-123] that attempt to eliminate this subjective element. The present study offers a third alternative, which is based on fitting a reparameterized form of the integrated Michaelis-Menten equation to the progress curves by non-linear regression. This method yields estimates and standard errors of the initial velocity and of the time to reach 50% reaction. No prior knowledge of the apparent product concentration at zero time or infinite time is required, since both of these quantities are also estimated from the data. It is shown that this method yields reliable estimates of the initial velocity under a wide range of circumstances, including those where the two previously published methods perform poorly.