Cold Pressor Stimulation Research Articles

Conditioned pain modulation and pain sensitivity in functional somatic disorders: The DanFunD study.

BackgroundDisrupted pain regulation has been proposed as a component in functional somatic disorders (FSD). The objective of this study was to examine a general population sample, encompassing three delimitations of FSD while assessing pain sensitivity and conditioning pain modulation (CPM).MethodsPressure pain thresholds (PPTs) at the tibialis and trapezius muscles were recorded at baseline. During cold pressor stimulation of the hand, the tibialis PPTs were re‐assessed and the difference from baseline measures defined the CPM effect. Participants (n = 2,198, 53% females) were randomly selected from the adult Danish population. FSD was established by self‐reported symptom questionnaires.ResultsWith a few exceptions, only weak associations were seen between PPTs and CPM in cases with FSD (p > .1). A high PPT was associated with lower odds of having multi‐organ bodily distress syndrome (ORPPT trapezius: 0.66, 95% CI: 0.49–0.88, p = .005), with the symptom profile characterized by all symptoms (ORPPT trapezius: 0.72, 95% CI: 0.58–0.90, p = .003 and ORPPT tibialis: 0.75, 95% CI: 0.62–0.91, p = .004), and with multiple chemical sensitivity (ORPPT trapezius: 0.81, 95% CI: 0.67–0.97, p = .022). High CPM was associated with high odds of having irritable bowel (ORCPM relative: 1.22, 95% CI: 1.04–1.43, p = .013 and ORCPM absolute = 2.66, 95% CI: 1.07–6.45, p = .033).ConclusionHowever, only PPT measured over the trapezius muscle were still significant after correction for multiple testing for the symptom profile characterized by all symptoms. Findings from this study do not support altered pain regulation in questionnaire‐based FSD which is in contrast with the existing presumption. Further epidemiological studies in this field are needed.SignificanceDisrupted pain regulation as measured by abnormal pain thresholds has been hypothesized as a central mechanism in Functional Somatic Disorders (FSD). The hypothesis has been raised in clinical setting where patients presented subjective and objective features of hypersensitivity. The present population‐based study does not support this notion. This points to the importance of further studies into the underlying pathophysiology mechanisms of FSD.

Progestin enhances vasoconstrictor responses in postmenopausal women receiving estrogen replacement therapy.

Clinical and experimental evidence suggests that the cardioprotective effect of estrogen replacement is due to effects both on scrum lipids and on blood vessels. Current practice includes the use of a progestin in combination with estrogen if the patient still has her uterus: however, little is known about the effects of combination therapy on vascular reactivity. We therefore studied the effects of estrogen alone and with added progestin on forearm vascular resistance at rest, during reactive hyperemia, and after cold pressor stimulation using plethysmography in six healthy, postmenopausal women. Measurements were made before therapy: after giving conjugated estrogen i.v.; followed by a daily oral dose of 0.625 mg for 21 days; and sequentially after the addition of 10 mg of medroxyprogesterone acetate (MPA) for 10 days. Mean blood pressure did not change significantly. After 21 days of estrogen therapy, forearm blood flow, resting vascular resistance, and resistance after cold pressor stimulation did not change significantly. However, after addition of MPA, resting forearm vascular resistance rose significantly from baseline: 25.7 ± 2.7 U (SE) versus 38.3 ± 2.5 (p = 0.004). In addition, forearm vascular resistance rose to a higher level after cold pressor stimulus during combination therapy (32.3 ± 5.9 vs. 58.4 ± 5.7; p = 0.0057) than after estrogen replacement alone (32.3 ± 5.9 vs. 37.7 ± 5.3; p = NS). We conclude that combination hormone replacement therapy results in higher resting vascular resistance and increased pressor responsiveness than does estrogen replacement therapy alone.

Preoperative Hypoalgesia After Cold Pressor Test and Aerobic Exercise is Associated With Pain Relief 6 Months After Total Knee Replacement.

Chronic pain after total knee replacement (TKR) is not uncommon. Preoperative impaired conditioning pain modulation (CPM) has been used to predict chronic postoperative pain. Interestingly, exercises reduce pain sensitivity in patients with knee osteoarthritis (KOA). This pilot study investigated the association between exercise-induced hypoalgesia (EIH) and CPM on post-TKR pain relief. Before and 6 months post-TKR, 14 patients with chronic KOA performed the cold pressor test on the nonaffected leg and 2 exercise conditions (bicycling and isometric knee extension), randomized and counterbalanced. Before and during the cold pressor test and after exercises test stimuli were applied to extract the pain sensitivity difference: computer-controlled cuff inflation on the affected lower leg until the participants detected the cuff pain threshold (cPPT) and subsequently the cuff pain tolerance (cPTT) and manual pressure pain thresholds (PPTs) at the legs, arm, and shoulder. Clinical pain intensity (numerical rating scale [NRS]) and psychological distress (questionnaires) were assessed. Clinical pain intensity, psychological distress, cPPT, and PPT at the affected leg improved post-TKR compared with pre-TKR (P<0.05). Preoperatively, the CPM and bicycling EIH assessed by the increase in cPTT correlated with reduction in NRS pain scores post-TKR (P<0.05). Improved CPM and EIH responses after TKR were significantly correlated with reduction in NRS pain scores post-TKR (P<0.05). In KOA patients, hypoalgesia after cold pressor stimulation and aerobic exercise assessed preoperatively by cuff algometry was associated with pain relief 6 months after TKR. EIH as a novel preoperative screening tool should be further investigated in larger studies.

Cortical and spinal assessment - a comparative study using encephalography and the nociceptive withdrawal reflex

BackgroundStandardized objective methods to assess the analgesic effects of opioids, enable identification of underlying mechanisms of drug actions in the central nervous system. Opioids may exert their effect on both cortical and spinal levels. In this study actions of morphine at both levels were investigated, followed by analysis of a possible correlation between the cortical processing and spinal transmission. MethodsThe study was conducted after a double-blinded, two-way crossover design in thirty-nine healthy participants. Each participant received 30mg morphine or placebo as oral solution in randomized order. The electroencephalogram (EEG) was recorded during rest and during immersion of the hand into ice-water. Electrical stimulation of the sole of the foot was used to elicit the nociceptive withdrawal reflex and the reflex amplitude was recorded. ResultsData from thirty subjects was included in the data analysis. There was no change in the activity in resting EEG (P>0.05) after morphine administration as compared to placebo. During cold pressor stimulation, morphine significantly lowered the relative activity in the delta (1–4Hz) band (P=0.03) and increased the activity in the alpha (8–12Hz) band (P=0.001) as compared to placebo. The reflex amplitudes significantly decreased after morphine administration (P=0.047) as compared to placebo. There was no correlation between individual EEG changes during cold pressor stimulation and the decrease in the reflex amplitude after morphine administration (P>0.05). ConclusionsCold pressor EEG and the nociceptive reflex were more sensitive to morphine analgesia than resting EEG and can be used as standardized objective methods to assess opioid effects. However, no correlation between the analgesic effect of morphine on the spinal and cortical assessments could be demonstrated.

Partial pharmacologic blockade shows sympathetic connection between blood pressure and cerebral blood flow velocity fluctuations

Cerebral autoregulation (CA) dampens transfer of blood pressure (BP)-fluctuations onto cerebral blood flow velocity (CBFV). Thus, CBFV-oscillations precede BP-oscillations. The phase angle (PA) between sympathetically mediated low-frequency (LF: 0.03–0.15Hz) BP- and CBFV-oscillations is a measure of CA quality. To evaluate whether PA depends on sympathetic modulation, we assessed PA-changes upon sympathetic stimulation with and without pharmacologic sympathetic blockade.In 10 healthy, young men, we monitored mean BP and CBFV before and during 120-second cold pressor stimulation (CPS) of one foot (0°C ice-water). We calculated mean values, standard deviations and sympathetic LF-powers of all signals, and PAs between LF-BP- and LF–CBFV-oscillations. We repeated measurements after ingestion of the adrenoceptor-blocker carvedilol (25mg). We compared parameters before and during CPS, without and after carvedilol (analysis of variance, post-hoc t-tests, significance: p<0.05).Without carvedilol, CPS increased BP, CBFV, BP-LF- and CBFV-LF-powers, and shortened PA. Carvedilol decreased resting BP, CBFV, BP-LF- and CBFV-LF-powers, while PAs remained unchanged. During CPS, BPs, CBFVs, BP-LF- and CBFV-LF-powers were lower, while PAs were longer with than without carvedilol. With carvedilol, CPS no longer shortened resting PA.Sympathetic activation shortens PA. Partial adrenoceptor blockade abolishes this PA-shortening. Thus, PA-measurements provide a subtle marker of sympathetic influences on CA and might refine CA evaluation.

Regulation of sympathetic nerve activity during the cold pressor test in normotensive pregnant and nonpregnant women.

Baseline neurovascular transduction is reduced in normotensive pregnancy; however, little is known about changes to neurovascular transduction during periods of heightened sympathetic activation. We tested the hypothesis that, despite an exacerbated muscle sympathetic nerve activity (microneurography) response to cold pressor stimulation, the blunting of neurovascular transduction in normotensive pregnant women would result in similar changes in vascular resistance and mean arterial pressure (Finometer) relative to nonpregnant controls. Baseline neurovascular transduction was reduced in pregnant women relative to controls when expressed as the quotient of both total resistance and mean arterial pressure and sympathetic burst frequency (0.32±0.07 versus 0.58±0.16 mm Hg/L/min/bursts/min, P<0.001 and 2.4±0.7 versus 3.6±0.8 mm Hg/bursts/min, P=0.001). Sympathetic activation was greater across all 3 minutes of cold pressor stimulation in the pregnant women relative to the nonpregnant controls. Peak sympathoexcitation was also greater in pregnant than in nonpregnant women, whether expressed as sympathetic burst frequency (+17±13 versus +7±8 bursts/min, P=0.049), burst incidence (+17±9 versus +6±11 bursts/100 hb, P=0.03), or total activity (+950±660 versus +363±414 arbitrary units, P=0.04). However, neurovascular transduction during peak cold pressor-induced sympathoexcitation remained blunted in pregnant women (0.25±0.11 versus 0.45±0.08 mm Hg/L/min/bursts/min, P<0.001 and 1.9±1.0 versus 3.2±0.9 mm Hg/bursts/min, P=0.006). Therefore, mean arterial pressure (93±21 versus 99±6 mm Hg, P=0.4) and total peripheral resistance (12±3 versus 14±3 mm Hg/L/min) were not different between pregnant and nonpregnant women during peak sympathoexcitation. These data indicate that the third trimester of normotensive pregnancy is associated with reductions in neurovascular transduction, which result in the dissociation of sympathetic outflow from hemodynamic outcomes, even during cold pressor-induced sympathoexcitation.

The acute effects of mental arithmetic, cold pressor and maximal voluntary contraction on arterial stiffness in young healthy subjects

BackgroundMental stress, dynamic exercise and cold pressor stimulation all increase blood pressure (BP); however, their effects on arterial stiffness are not well described. MethodsTwenty-three young healthy subjects (14 female/9 males), aged 18–30 years (23 ± 3 years), underwent mental arithmetic stress (mental arithmetic test [MAT]), cold presser test (CPT) and dynamic exercise (30% of maximal voluntary contraction [30% MVC]). Blood pressure and indices of arterial stiffness, pulse wave velocity (PWV; m/sec) and augmentation index (AIx; %) were measured at baseline, during the intervention (MAT, CPT and 30% MVC), and at 5 min and 10 min after the end of the intervention on separate days within a 3-week period. All values are given as means and standard deviations; statistical analysis was carried out using JMP software (Version 7). ResultsDuring MAT, CPT and 30% MVC there were respective increases in heart rate (HR/min) 27%, 16% and 10% (P < 0.001); systolic BP 16%, 17% and 12% (P < 0.01); diastolic BP 15%, 23% and 15% (P < 0.01); AIx 13%, 29% and 30% (P < 0.05); and PWV 14%, 12% and 16% (P < 0.01). When the model was corrected for HR, systolic BP and diastolic BP the changes both in PWV and AIx remained significant (P < 0.01). ConclusionsMAT, CPT and 30% MVC each increase the indices of arterial stiffness independently of HR and baseline blood pressure levels.

Similarities between exercise-induced hypoalgesia and conditioned pain modulation in humans

Pain inhibitory mechanisms are often assessed by paradigms of exercise-induced hypoalgesia (EIH) and conditioned pain modulation (CPM). In this study it was hypothesized that the spatial and temporal manifestations of EIH and CPM were comparable. The participants were 80 healthy subjects (40 females), between 18 and 65years of age in this randomized, repeated-measures cross-over trial that involved data collection on 2 different days. CPM was assessed by 2 different cold pressor tests (hand and foot). EIH was assessed by 2 intensities of aerobic bicycling exercises and 2 intensities of isometric muscle contraction exercises (arm and leg). Pressure pain thresholds (PPTs) were recorded before, during, after, and 15minutes after conditioning/exercise at sites local to and remote from the extremity used for cold pressor stimulation and exercise. PPTs increased at local as well as at remote sites during both cold pressor tests and after all of the exercise conditions except low-intensity bicycling. EIH after bicycling was higher in women than in men. CPM and the EIH responses after isometric exercises were comparable in men and women and were not affected by age. The EIH response was larger in the exercising body part compared with nonexercising body parts for all exercise conditions. High-intensity exercise produced greater EIH responses than did low-intensity exercise. The change in PPTs during cold pressor tests and the change in PPTs after exercises were not correlated. The CPM response was not dominated by local manifestations, and the effect was seen only during the stimulation, whereas exercise had larger local manifestations, and the effects were also found after exercise.

Hyper-arousal decreases human visual thresholds.

Arousal has long been known to influence behavior and serves as an underlying component of cognition and consciousness. However, the consequences of hyper-arousal for visual perception remain unclear. The present study evaluates the impact of hyper-arousal on two aspects of visual sensitivity: visual stereoacuity and contrast thresholds. Sixty-eight participants participated in two experiments. Thirty-four participants were randomly divided into two groups in each experiment: Arousal Stimulation or Sham Control. The Arousal Stimulation group underwent a 50-second cold pressor stimulation (immersing the foot in 0–2° C water), a technique known to increase arousal. In contrast, the Sham Control group immersed their foot in room temperature water. Stereoacuity thresholds (Experiment 1) and contrast thresholds (Experiment 2) were measured before and after stimulation. The Arousal Stimulation groups demonstrated significantly lower stereoacuity and contrast thresholds following cold pressor stimulation, whereas the Sham Control groups showed no difference in thresholds. These results provide the first evidence that hyper-arousal from sensory stimulation can lower visual thresholds. Hyper-arousal's ability to decrease visual thresholds has important implications for survival, sports, and everyday life.

Improvement in arousal, visual neglect, and perception of stimulus intensity following cold pressor stimulation

The relationship between arousal, perception, and visual neglect was examined in this case study. Cold pressor stimulation (CPS: immersing the foot in iced water) was used to manipulate arousal and to determine its effects on contralesional neglect, perception of stimulus intensity (magnitude estimation), reaction time, and an electrophysiological correlate of ascending reticular activating system activity (i.e., the P50 potential). Measures that normalized from baseline following CPS included contralesional neglect on a clock drawing test, perception of stimulus magnitude, and P50 amplitude. The P50 amplitude returned to its abnormally low baseline level 20 min after CPS ended, indicating that CPS increased arousal.

Cold pressor stimulation diminishes P50 amplitude in normal subjects.

The present study examined how cold pressor stimulation influences electrophysiological correlates of arousal. We measured the P50 auditory evoked response potential in two groups of subjects who immersed their foot in either cold (0-2°C) or room temperature (22-24°C) water for 50 seconds. The P50, which was recorded before and after stimulation, is sleep-state dependent and sensitive to states of arousal in clinical populations. We found a significant reduction in P50 amplitude after exposure to cold, but not room temperature water. In comparison with other studies, these results indicate that cold pressor stimulation in normal subjects may evoke a regulatory process that modulates the P50 amplitude, perhaps to preserve the integrity of sensory perception, even as autonomic and subjective aspects of arousal increase.

Noninvasive intracranial hypertension detection based on cerebral blood flow velocity waveform alone

Cerebral autoregulation (CA) dampens transfer of blood pressure (BP)-fluctuations onto cerebral blood flow velocity (CBFV). Thus, CBFV-oscillations precede BP-oscillations. The phase angle (PA) between sympathetically mediated low-frequency (LF: 0.03–0.15 Hz) BP- and CBFV-oscillations is a measure of CA quality. To evaluate whether PA depends on sympathetic modulation, we assessed PA-changes upon sympathetic stimulation with and without pharmacologic sympathetic blockade.In 10 healthy, young men, we monitored mean BP and CBFV before and during 120-second cold pressor stimulation (CPS) of one foot (0 °C ice-water). We calculated mean values, standard deviations and sympathetic LF-powers of all signals, and PAs between LF-BP- and LF–CBFV-oscillations. We repeated measurements after ingestion of the adrenoceptor-blocker carvedilol (25 mg). We compared parameters before and during CPS, without and after carvedilol (analysis of variance, post-hoc t-tests, significance: p < 0.05).Without carvedilol, CPS increased BP, CBFV, BP-LF- and CBFV-LF-powers, and shortened PA. Carvedilol decreased resting BP, CBFV, BP-LF- and CBFV-LF-powers, while PAs remained unchanged. During CPS, BPs, CBFVs, BP-LF- and CBFV-LF-powers were lower, while PAs were longer with than without carvedilol. With carvedilol, CPS no longer shortened resting PA.Sympathetic activation shortens PA. Partial adrenoceptor blockade abolishes this PA-shortening. Thus, PA-measurements provide a subtle marker of sympathetic influences on CA and might refine CA evaluation.

Autonomic cardiovascular control and responses to experimental pain stimulation in fibromyalgia syndrome

Objective This study involves a comprehensive investigation of autonomic cardiovascular regulation in fibromyalgia syndrome (FMS) at rest and during painful stimulation and its association with pain indices. Methods In 35 patients and 29 healthy controls, electrocardiography, impedance cardiography, and finger continuous blood pressure measurements were conducted. For the purpose of experimental pain induction, a cold pressor test was applied. Results FMS patients showed lower pain threshold and tolerance, as well as higher ratings of pain intensity and unpleasantness on visual analogue scales. Resting stroke volume, myocardial contractility, R-R interval, heart rate variability, and sensitivity of the cardiac baroreflex were reduced in the patients, and increases in stroke volume and myocardial contractility during cold pressor stimulation were less pronounced. In the whole sample as well as in the FMS group, baroreflex sensitivity was inversely associated with subjective pain intensity, and a higher number of baroreflex operations per unit of time predicted higher pain tolerance. Conclusions The data suggest impaired autonomic cardiovascular regulation in FMS in terms of reduced sympathetic and parasympathetic influences, as well as blunted sympathetic reactivity to acute stress. The association between baroreflex function and pain experience reflects the pain inhibition mediated by the baroreceptor system. Given the reduced baroreflex sensitivity in FMS, one may assume deficient ascending pain inhibition arising from the cardiovascular system, which may contribute to the exaggerated pain sensitivity of FMS.

When does cortical arousal enhance performance in visual perception tasks?

Intro: Cold pressor stimulation (CPS, immersing the foot in ice-water for 50 seconds) decreases contrast thresholds without changing verbal distance estimates (Woods et al., 2009). Apparently, enhancing cortical arousal influences some visual tasks but not others. The factors that elicit this influence remain unclear. To begin investigating this issue, we conducted two experiments representing intermediate steps between the contrast threshold and verbal distance estimation methodologies: a Depth Threshold task (modeled on the 2AFC contrast threshold methodology, but in the depth domain) and a Distance Difference Threshold task (similar to the Depth task but with targets presented successively rather than in pairs). Methods: Depth Threshold: Two groups (N's = 18) underwent either CPS or “Sham” stimulation (immersing the foot in room temperature water for 50 seconds). On each trial participants binocularly viewed two white rods against a black background and judged which rod was closer, with depth separation being adjusted adaptively across trials. Threshold (82% correct criterion) was estimated before and after stimulation. DistanceDifference Threshold: Seventeen participants sequentially viewed 2 cones in identical checkerboard-covered alleyways (interstimulus interval ≈ 1.5s), judging which cone was closer. Thresholds were determined before and after CPS. Distance difference was adjusted adaptively across trials. Results: Depth thresholds decreased following CPS (t=3.4, p=0.003), but remained unchanged following Sham stimulation (t=0.19, p=0.84). Distancedifference thresholds did not change from Baseline to Post-Stimulation (t=0.21, p=0.83). Discussion: When present, arousal-related affects could stem from either enhanced attention or bona-fide changes in visual appearance. These factors are difficult to tease apart. In a separate experiment, we found that CPS did not affect contrast thresholds in a 2AFC task when the interstimulus interval was increased to 1.5 s. Thus, our results suggest that some aspect of the simultaneous or near-simultaneous comparison between stimuli may be crucial for eliciting arousal-related effects in visual tasks.

Evaluation of coronary endothelial dysfunction in healthy young smokers: Cold pressor test using [ 15O]H 2O PET

The purpose of this study was to investigate coronary endothelial dysfunction in young healthy smokers by measuring myocardial blood flow (MBF) using [ 15O]H 2O-PET. The study population was 18 young male volunteers consisted of 9 smokers (age: 23.8±1.1 yr) and 9 non-smokers (age: 25.0±2.5 yr). The smokers had been smoking cigarettes for 6.6±2.5 pack years. Myocardial [ 15O]H 2O-PET was performed at rest, during cold (5 °C) pressor stimulation and during adenosine infusion. Left ventricular (LV) input function and tissue time–activity curves were obtained by drawing region of interest (ROI) on the LV blood pool and myocardium images obtained by non-negative matrix factorization (NMF) of dynamic [ 15O]H 2O-PET data, and MBF was calculated using these time–activity curves and single compartmental model. There were no significant difference in resting MBF between two groups (smokers: 1.43±0.41 and non-smokers: 1.37±0.41 ml/g/min; P=NS). However, during cold pressor stimulation, MBF in smokers was significantly lower than that in non-smokers (1.25±0.33 vs. 1.59±0.29 ml/g/min; P=0.019). MBF changed to 90±24% of resting MBF in smokers and 122±28% in non-smokers. The difference in the ratio of cold pressor MBF to basal MBF between two groups was also significant ( P=0.024). During adenosine infusion, however, hyperemic MBF did not differ significantly between smokers and non-smokers (5.81±1.99 vs. 5.03±1.27 ml/g/min; P=NS). This study shows that [ 15O]H 2O PET analysis can reveal that endothelial dysfunction occurs in even young smokers of about 6 pack years.

Effect of heterotopic noxious conditioning stimulation on electrical and pressure pain thresholds in two different anatomical regions

Objectives. The aims of the study were to investigate the influence of heterotopic noxious conditioning stimulation (HNCS) on pain thresholds in the orofacial and spinal regions and to find out whether there are gender differences in this respect. Material and Methods. Thirty healthy subjects (15 of each sex) with a mean (SD) age of 25.1 (4.4) years participated. Pain thresholds to electrical (EPT) and pressure stimuli (PPT) were recorded in the masseter muscle and 1st upper incisor (tooth), as well as in the fingertip, before, during, and 5 and 15 min after a cold pressor task to the contralateral hand immersed in ice-cold water for a maximum of 5 min. Results. With the exception of the EPT in the orofacial region, all pain thresholds increased during the HNCS and then returned to baseline during the 15 min follow-up. The significant changes in EPT were greater in the finger than in the tooth, while the changes in PPT were greater in the masseter muscle than in the finger. Electrical stimuli in the finger induced greater significant changes of pain thresholds than pressure. In the orofacial region, pressure induced greater significant changes in pain thresholds during HNCS than electrical stimuli did. The HNCS induced pain of high intensity and unpleasantness, i.e. varying between 5 and 10 on the numeric rating scale (NRS). There were no gender differences in the response to the HNCS. Conclusion. We conclude that, in general, HNCS induced by cold pressor stimulation increases pain thresholds, but the magnitude of the effect differs between the orofacial region and the finger and is influenced by the tissue and type of test stimuli.

Responses of the hypothalamic–pituitary–adrenal axis and pain threshold changes in the orofacial region upon cold pressor stimulation in normal volunteers

Aim This study focused on the relationship between the HPA axis function and the heat pain threshold in the orofacial region upon cold pressor (CP) stimulation. Methods Ten healthy male individuals participated in this study. CP stimulation was applied to each participant, and their peripheral blood was collected 5 min before, during and 5, 15, 30, 45, 60 min after receiving CP. In addition, 5 of those 10 participants were selected at random and they experienced a mock CP trial on different days. The heat pain thresholds on the facial skin about 10 mm anterior to the right external auditory canal (trigeminal V2 region) in each subject were simultaneously recorded 5 min before and 5, 30, 60 min after CP stimulation. The blood pressure and heart rate were continuously monitored throughout the course of the CP and mock trials using an electric blood pressure meter. Results Significant increases in the plasma concentration of cortisol, β-endorphin and ACTH were induced by CP stimulation, while no significant increases were observed under the mock trial conditions. The blood pressure and heart rate showed concomitant increases during CP stimulation. In addition, the heat pain threshold in the orofacial region significantly increased after receiving CP stimulation. These results suggest that CP stimulation activated the HPA axis thereby increasing the heat pain threshold in the orofacial region in healthy individuals. Conclusions This observed pain threshold increase might be due to the activation of an endogenous opioid system, such as increase in the circulating β-endorphin levels.

Abnormal endogenous pain modulation and somatic and visceral hypersensitivity in female patients with irritable bowel syndrome

To investigate the role of endogenous pain modulatory mechanisms in the central sensitization implicated by the visceral hypersensitivity demonstrated in patients with irritable bowel syndrome (IBS). Dysfunction of modulatory mechanisms would be expected to also result in changes of somatic sensory function. Endogenous pain modulatory mechanisms were assessed using heterotopic stimulation and somatic and visceral sensory testing in IBS. Pain intensities (visual analogue scale, VAS 0-100) during suprathreshold rectal distension with a barostat, cold pressor stimulation of the foot and during both stimuli simultaneously (heterotopic stimulation) were recorded in 40 female patients with IBS and 20 female healthy controls. Rectal hypersensitivity (defined by 95% CI of controls) was seen in 21 (53%), somatic hypersensitivity in 22 (55%) and both rectal and somatic hypersensitivity in 14 of these IBS patients. Heterotopic stimulation decreased rectal pain intensity by 6 (-11 to -1) in controls, but increased rectal pain by 2 (-3 to +6) in all IBS patients (P < 0.05) and by 8 (-2 to +19) in IBS patients with somatic and visceral hypersensitivity (P < 0.02). A majority of IBS patients had abnormal endogenous pain modulation and somatic hypersensitivity as evidence of central sensitization.

A comparison of the effects of preferred music, arithmetic and humour on cold pressor pain

Research studies of ‘audioanalgesia’, the ability of music to affect pain perception, have significantly increased in number during the past two decades. Listening to preferred music in particular may provide an emotionally engaging distraction capable of reducing both the sensation of pain itself and the accompanying negative affective experience. The current study uses experimentally induced cold pressor pain to compare the effects of preferred music to two types of distracting stimuli found effective within the previous studies; mental arithmetic, a cognitive distraction, and humour, which may emotionally engage us in a similar manner to music. Forty-four participants (24 females, 20 males) underwent three cold pressor trials in counterbalanced order. The Paced Auditory Serial Addition Task provided the cognitive distraction and a choice was given from three types of audiotaped stand-up comedy. Participants provided their own preferred music. A circulating and cooling water bath administered cold pressor stimulation. Tolerance time, pain intensity on visual analogue scale and the pain rating index and perceived control were measured. Preferred music listening was found to significantly increase tolerance in comparison to the cognitive task, and significantly increase perceived control in comparison to humour. Ratings of pain intensity did not significantly differ. The results suggest preferred music listening to offer effective distraction and enhancement of control as a pain intervention under controlled laboratory conditions.

Aberrant Neural Responses to Cold Pressor Challenges in Congenital Central Hypoventilation Syndrome

Patients with congenital central hypoventilation syndrome (CCHS), a condition characterized by impaired ventilatory responses to chemoreceptor stimulation, do not show the normal increase in respiratory rate and respiratory-related heart rate variation to cold forehead stimulation, a challenge that bypasses central chemoreceptors. We hypothesized that a forehead cold pressor challenge would reveal abnormal neural response patterns, as assessed by functional magnetic resonance imaging, in brain regions that are responsible for the integration of cold afferent stimulation with respiratory and cardiovascular output in patients with CCHS. Primary sensory thalamic and cortical areas for the forehead showed diminished responses in 13 patients with CCHS (ventilator dependent during sleep but not waking, no Hirschsprung's disease) compared with 14 control subjects, despite initial signal changes in the cortex being similar in both groups. Cerebellar cortex and deep nuclei; basal ganglia; and middle to posterior cingulate, insular, frontal, and temporal cortices showed reduced signal rises in patients with CCHS. Areas within the frontal and anterior cingulate cortices exhibited marked signal declines in control subjects but little change in patients with CCHS. No response occurred in either group in the dorsal medulla, but medial and ventral medullary areas showed enhanced signals in patients with CCHS. The cold pressor stimulation did not recruit dorsal medullary sites that would be affected by PHOX2B (a mutation of which is associated with the syndrome) expression in either group but demonstrated deficient cerebellar and medial medullary influences that, by action on rostral sites, may underlie the loss of respiratory responses.