Adaptive modifications of cold pain. III. Communication: short-term experiments with 1-min-intervals (author's transl)

The subjective short-term habituation to pain-inducing cold stimuli is demonstrated for the first time by measuring the tolerated exposition time. It proves impossible to separate temporally a detection threshold of cold pain from the distress reaction level. The slope of subjective habituation is clearly dependent on the individual vegetative starting position. It is discussed why the blood pressure reaction may be used as a valid parameter for experienced intensity of a cold pain sensation only to a limited extent.     

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.     

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.     

Double-Cone Coil TMS Stimulation of the Medial Cortex Inhibits Central Pain Habituation

Objective

The aim of this study was to investigate whether Transcranial Magnetic Stimulation (TMS) applied over the medial line of the scalp affects the subjective perception of continuous pain induced by means of electric stimulation. In addition, we wanted to identify the point of stimulation where this effect was maximum.

Methods

Superficial electrical stimulation was used to induce continuous pain on the dominant hand. At the beginning of the experiment we reached a pain rating of 5 on an 11-point numeric rating scale (NRS; 0 = no pain and 10 = maximum tolerable pain) for each subject by setting individually the current intensity. The TMS (five pulses at increasing intensities) was applied on 5 equidistant points (one per session) over the medial line of the scalp in 13 healthy volunteers using a double-cone coil to stimulate underlying parts of the brain cortex. In every experimental session the painful stimulation lasted 45 minutes, during which pain and distress intensities NRS were recorded continuously. We calculated the effect of adaptation and the immediate effect of the TMS stimulation for all locations. Additionally, an ALE (Activation Likelihood Estimation) meta-analysis was performed to compare our results with the neuroimaging literature on subjective pain rating.

Results

TMS stimulation temporarily decreased the pain ratings, and pain adaptation was suppressed when applying the TMS over the FCz site on the scalp. No effect was found for distress ratings.

Conclusions

The present data suggest that the medial cortex in proximity of the cingulated gyrus has a causal role in adaptation mechanisms and in processing ongoing pain and subjective sensation of pain intensity.     

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.     

Effects of ozone exposure on four consecutive days on work performance and VO2max

The effects of 4 consecutive days of 1-h exposure to 0.35 ppm ozone (O3) on maximal O2 uptake (VO2max), performance time, pulmonary function, and subjective symptom responses were studied in eight aerobically trained males. Each subject was first exposed in random order to filtered air (FA) and 0.35 ppm O3 while exercising on a bicycle ergometer for 50 min at a work load eliciting minute ventilation of approximately 60 1/min. A rapidly incremented VO2max test to volitional fatigue was completed within 10 min following each of these exposures, as well as on day 4 of the consecutive daily exposures to O3. Initial exposure to O3 induced the occurrence of subjective symptoms, as well as significant pulmonary function impairment and decrements in maximal exercise performance time (from 253 to 211 s) and VO2max (from 3.85 to 3.62 l/min). Following the fourth consecutive day of exposure to O3, pulmonary function impairment was not significantly different from initial exposure to O3, although subjective symptom severity was significantly reduced. Exercise performance time (239 s) and VO2max (3.79 l/min) on the fourth consecutive daily exposure to O3 were not significantly different from FA values. These data indicate no significant adaptation to initial O3 exposure-induced pulmonary function impairment following four consecutive daily exposures to O3, although reduced subjective symptom severity and enhanced exercise performance time on day 4 suggest an habituation effect. Our results also suggest that O3 adaptation may be a more complex phenomena than identified previously.     

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.     

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.     

The effect of a vasopressin analog on the reaction of the command neurons in the defensive behavior of the edible snail during nerve stimulation

On the level of snail command neurones of the defensive behaviour an increase was revealed of the amplitude of summary EPSP recorded in command neurones in response to nerve stimulation, an increase of probability of appearance of action potential in the reaction and, under certain conditions, a significant decrease of habituation speed at rhythmic (0.1 Hz) nerve stimulation against the background of peptide. The latter effect was found during comparison of groups of neurones--control neurones and those to which the peptide was presented before the first series of stimulation in the test, i. e. without preliminary elaboration of habituation. The decrease of the speed of habituation concerned both the amplitude of summary EPSP and the probability of action potential appearance in the reaction. All these changes against the background of vasopressin analogue may be the basis of the increase of spike reactions of command neurones of the defensive behaviour and thus the basis of the initiation or the increase of behavioural defensive reactions. The obtained effects were not protracted and took place only in the presence of the peptide in the extracellular medium.     

Visceral orienting reflexes as significant components of psychophysiologic personality assessment

Activ. nerv. sup. (Praha) 28, 2, 1986. Utilizing a combination of idiographic and nomothetic research designs with repeated measures in several breeds of dogs, we discovered stable constitutional differences in psychophysiologic reactions to repeated exposure to psychologically stressful situations. Some dogs showed high psychophysiologic adaptation (HA dogs). Other dogs developed persistent psychophysiologic reactions to the psychologically aversive environment: tachycardia, polypnea, profuse salivation, high energy metabolism and muscle tension, and high urinary vasopressin and catecholamines (low adaptation or LA dogs). Retrospective analysis of the development and extinction of cardiac and respiratory orienting reflexes (OR) in these two types of dogs revealed that the LA dogs exhibit higher frequency and more intense, persistent and highly fluctuating (poorly modulated) cardiac and respiratory OR than the HA dogs, which show rapid OR habituation and good modulation. Insofar as one may extrapolate these data to human subjects, recording dynamics of development and habituation and degree of modulation of visceral OR may facilitate early detection of individuals at risk for cardiorespiratory and other psychovisceral disorders.     

Exposure to an inhomogeneous static magnetic field increases thermal pain threshold in healthy human volunteers

In the present experiment, the effect of a single 30 min inhomogeneous static magnetic field (SMF) exposure on thermal pain threshold (TPT) was examined in 15 young healthy human volunteers. The SMF had a maximum peak‐to‐peak amplitude of 330 mT with a maximum gradient of 13.2 T/m. In either of two experimental sessions (SMF or SHAM), four blocks of 12 TPT trials were carried out under SMF or SHAM exposure on all fingertips of the dominant hand, excluding the thumb. TPT and visual analog scale (VAS) data were recorded at 0, 15, and 30 min exposure time, and 30 min following exposure. SMF treatment resulted in a statistically significant increase in TPT during the entire exposure duration and diminished within‐block thermal habituation, leaving pain perception unchanged. These results indicate that SMF‐induced peripheral neuronal or circulatory mechanisms may be involved in the observed TPT increase by setting the pain fibre adaptation potential to higher levels. Bioelectromagnetics 32:131–139, 2011. © 2010 Wiley‐Liss, Inc.     

Sustained release of corticosterone in rats affects reactivity, but does not affect habituation to immobilization and acoustic stimuli

Depression is often preceded by stressful life events and accompanied with elevated cortisol levels and glucocorticoid resistance. It has been suggested that a major depressive disorder may result from impaired coping with and adaptation to stress. The question is whether or not hypothalamus-pituitary-adrenal (HPA)-axis dysfunction influences the process of adaptation. We examined the effect of a dysregulated HPA-axis on the adaptation to acoustic stimuli in rats with or without preceding restraint stress. HPA-axis function was altered via slow release of corticosterone (CORT, 90 mg) from subcutaneously implanted pellets for 7 or 14 days. The rate of body temperature increases during restraint (10 min) and the response to acoustic stimuli (of 80+120 dB) were used to quantify daily stress reactivity. Rats habituated to either stress regardless of CORT treatment. CORT treatment combined with restraint decreased the initial reactivity and the variability in response, but the rate of habituation was not influenced. These results show that suppressing normal HPA-axis function by chronic exposure to CORT does affect the course of habituation, but not habituation per se. This implies that altered HPA-axis function in depressed patients may not be causally related to stress coping, but instead may influence the course of the disorder.     

Comparative acid stress response of Listeria monocytogenes, Escherichia coli O157:H7 and Salmonella Typhimurium after habituation at different pH conditions

AIMS: The aim of the study was to evaluate the effect of habituation at different pH conditions on the acid resistance of Listeria monocytogenes, Escherichia coli O157:H7 and Salmonella enterica serotype Typhimurium, and to identify potential differences between the adaptive responses of the three pathogens. METHODS: Stationary phase cells of L. monocytogenes, E. coli O157:H7 and S. Typhimurium, grown in glucose-free media, were exposed to pH 3.5 broth directly or after habituation for 90 min at various pH conditions from 4.0 to 6.0. Survivors at pH 3.5 were determined by plating on tryptic soy agar and incubating at 30 degrees C for 48 h. The kinetics (death rate) of the pathogens at pH 3.5 was calculated by fitting the data to an exponential model. RESULTS: Habituation to acidic environments provided protection of the pathogens against lethal acid conditions. This acid protection, however, was found to be pH dependent. For example, for E. coli O157:H7 an increased acid resistance was observed after habituation at a pH range from 4.0 to 5.5, while the maximum acid tolerance was induced at pH 5.0. Furthermore, the effect of low pH habituation was different among pathogens. For L. monocytogenes, E. coli O157:H7 and S. Typhimurium, the pH range within which habituation resulted to increased acid resistance was 5.0-6.0, 4.0-5.5 and 4.0-5.0, respectively, while the maximum acid tolerance was induced after habituation at pH 5.5, 5.0 and 4.5, respectively. SIGNIFICANCE: Acid stress conditions are common within current food processing technologies. The information on adaptive responses of L. monocytogenes, E. coli O157:H7 and S. Typhimurium after habituation to different pH environments provided in the present study, could lead to a more realistic evaluation of food safety concerns and to a better selection of processes in order to avoid adaptation phenomena and to minimize the potential for food safety risks.     

Ranging Patterns of a Western Gorilla Group During Habituation to Humans in the Dzanga-Ndoki National Park,Central African Republic

The ranging patterns of western gorillas have been described in relation to their more frugivorous diet as compared to mountain gorillas. However, the lack of data from habituated groups prevents a full understanding of their ranging behavior and its implications for western gorilla social behavior. Unhabituated gorillas often flee from approaching researchers, possibly resulting in longer daily ranges and home range expansions and/or shifts. I report on the influence of habituation on the ranging patterns of a western gorilla group. I analyzed progress in habituation through changes in gorilla reactions, displayed upon detecting the observers. I measured daily path length and home range while following the group's trails and monitored diet via fecal analyses and direct observations. During the study period, habituation progressed and the gorillas increasingly ignored the arrival of observers. As a result, daily path lengths were longer during the early stages of habituation, when the gorillas were avoiding observers. There was no range expansion or shift, though the measure is more difficult to investigate, being subject to error due to variation in sample size. We recorded seasonal changes in the consumption of fruit by gorillas, but no direct effect on ranging patterns is detectable with the data available, which is likely a consequence of the combined effect of habituation and seasonality on group movements. The findings are not only important for understanding the extent of human influence while conducting research on wild gorillas but also suggest the need for caution when interpreting results from non-habituated gorillas.     

Coping with the cold: the cold shock response in the Gram-positive soil bacterium Bacillus subtilis

All organisms examined to date, respond to a sudden change in environmental temperature with a specific cascade of adaptation reactions that, in some cases, have been identified and monitored at the molecular level. According to the type of temperature change, this response has been termed heat shock response (HSR) or cold shock response (CSR). During the HSR, a specialized sigma factor has been shown to play a central regulatory role in controlling expression of genes predominantly required to cope with heat-induced alteration of protein conformation. In contrast, after cold shock, nucleic acid structure and proteins interacting with the biological information molecules DNA and RNA appear to play a major cellular role. Currently, no cold-specific sigma factor has been identified. Therefore, unlike the HSR, the CSR appears to be organized as a complex stimulon rather than resembling a regulon. This review has been designed to draw a refined picture of our current understanding of the CSR in Bacillus subtilis. Important processes such as temperature sensing, membrane adaptation, modification of the translation apparatus, as well as nucleoid reorganization and some metabolic aspects, are discussed in brief. Special emphasis is placed on recent findings concerning the nucleic acid binding cold shock proteins, which play a fundamental role, not only during cold shock adaptation but also under optimal growth conditions.     

Effect of electroacupuncture on the nature of changes in the activity of neurons in the 2d somatosensory region of the cerebral cortex

Effects of electroacupuncture (EAP) on the character of spontaneous and evoked neuronal impulse activity changes in the second somatosensory area (S2) of the brain cortex by nociceptive and non-nociceptive stimulation were studied in acute experiments on cats. It was demonstrated that EAP changed the character of S2 neurons activity and formed their new functional state. After EAP activity of non-nociceptive neurons were not changed, evoked activity of nociceptive neurons were inhibited. It is suggested, that EAP preferential blocking the protopathic components of the acute pain.     

Effect of piracetam on the habituation of the neuronal cholinoreceptor membrane of the edible snail

Piracetam is shown to modulate the habituation pattern of cholinoreceptor neuronal membrane in Helix lucorum. Piracetam (10(-2) M) intensified the reversible decrease of depolarization and spike discharge induced by the local microionophoretic rhythmical application of acetylcholine to the neuron soma. The ability of piracetam to intensify the habituation of neuronal cholinoreceptor membrane may serve as a model of its facilitating effect on the development of habituation of behavioural reactions. Piracetam (5.10(-2) M) was shown to induce a shift in the membrane potential towards depolarization in the majority of identified neurons studied.     

Effects of barefoot habituation in winter on thermal and hormonal responses in young children--a preliminary study

This study investigated how socks-wearing habit or habitual barefoot in the cold winter affected skin temperatures of distal lower extremities, the urinary excretion of adrenaline, noradrenaline and cortsisol in young children. In Experiment I for preschool children, the measurements of foot and leg skin temperatures were conducted for 30 min in the classroom controlled at 23+/-2 degres C and 50+/-5%RH, and the excretion of urinary catecholamines and cortisol during nocturnal sleep were analyzed. In Experiment II for elementary school children, nocturnal secretion of urinary catecholamines and cortisol was analyzed. While leg skin temperature tended to be lower in barefoot group than in socks group during Experiment I, foot skin temperature was not significantly different between the two groups. Fall of leg skin temperature during 30 min measurement tended to be smaller in barefoot group than in socks group. Urine volume and urinary excretion of cortisol tended to be greater in barefoot group than in socks group for preschool children. Urinary noradrenaline was significantly greater and cortisol tended to be greater in barefoot group than in socks group for elementary school children. Considering that most of the findings shown above were in the proximity of the established level of statistical significance, it was provisionally concluded that young children with barefoot habituation might show more effective cold adaptation of metabolic type than those without the habituation do, by keeping their skin temperatures higher even in the cold and enhancing the metabolic rate.