Cold Pain Intensity Research Articles

Weak Relationships Between Psychological Factors and Experimental Pain Outcomes in Pain-Free Individuals: An Aggregate Analysis of 8 Studies

Although psychological factors such as anxiety, depression, and pain catastrophizing are known to influence pain outcomes in chronic pain populations, there are mixed results regarding whether they influence experimental pain outcomes in pain-free individuals. The objectives of this study were to determine the associations between psychological factors and experimental pain outcomes in pain-free adolescents and adults. Relationships between anxiety, depression, and pain catastrophizing and experimental pain outcomes across 8 different studies (total N = 595) were examined in different populations of pain-free adult and adolescent participants. Analyses were conducted with and without controlling for sex, age, and race. Studies were analyzed separately and as part of an aggregate analysis. Individual study analyses resulted in 136 regression models. Of these, only 8 models revealed a significant association between psychological factors and pain outcomes. The significant results were small and likely due to Type 1 error. Controlling for demographic factors had minimal effect on the results. The aggregate analyses revealed weak relationships between anxiety and pressure pain threshold (Fisher’s z = −.10 [−.19, −.01]), anxiety and cold pain intensity ratings (Fisher’s z = .18 [.04, .32]), and pain catastrophizing and pressure pain threshold (Fisher’s z = −.14 [−.26, −.02]). Sample size calculations based on the aggregate analyses indicated that several hundred participants would be required to detect true relationships between these psychological factors and pain measures. The overall negative findings suggest that in pain-free individuals, anxiety, depression, and pain catastrophizing are not meaningfully related to experimental pain outcomes. PerspectivePsychological variables have been shown to predict pain outcomes in chronic pain populations but these relationships may not generalize to pain-free populations. An analysis of 595 pain-free individuals across 8 studies in our lab revealed that anxiety, depression, and pain catastrophizing were not meaningfully related to experimental pain outcomes.

Effects of an afforestation activity on thermal and mechanical pain mechanisms: A clinical trial

Sensory stimulation has shown the capacity to modulate pain mechanisms. Yet, the optimal methods of sensory stimulation remain uncertain. Afforestation activities stand out as a potential stimulation method, as they allow individuals to interact with multisensory stimuli produced in green environments. Exposure to natural multisensory stimuli has been shown to induce neurobiological activations in pain-related brain areas in healthy populations. However, the possible impact of the natural multisensory stimuli on the pain mechanisms themselves is yet to be explored. This study aimed to investigate the potential effects of sensory stimulation experienced during participation in an afforestation program on thermal and mechanical pain mechanisms. A single-group, pretest-posttest clinical trial was used. Forty-seven healthy adults performed an afforestation activity for 90 minutes. Measurements included cold pain detection and tolerance thresholds via the Cold Pressor Test, wind-up and mechanical pain sensitivity through a pinprick stimulator, and pressure pain detection and tolerance thresholds utilizing pressure algometry. For both thermal and mechanical pain thresholds, pain intensity was assessed using the 101-point Numeric Rating Scale. The results showed significant reductions in the cold pain intensity at the moment of detection (p = .046), mechanical pain sensitivity (p ≤ .014), and increases in the thresholds of pressure pain detection (p = .005) and tolerance (p ≤ .046). Therefore, the interaction with natural multisensory stimuli could be a possible therapeutic strategy to positively modulate mechanical pain sensitivity and pressure pain thresholds.

Virtual reality hypnosis diminishes experimental cold pain and alters autonomic responses.

Immersive virtual reality (VR) is a promising tool to reduce pain in clinical setting. Digital scripts displayed by VR disposals can be enriched by several analgesic interventions, which are widely used to reduce pain. One of these techniques is hypnosis induced through the VR script (VRH) which is facilitated by immersive environment and particularly efficient even for low hypnotizable patients. The aim of this study is to assess the efficacy of a VRH script on experimentally induced cold pain perception (intensity and unpleasantness) and physiological expression. 41 healthy volunteers had been recruited in this within-subjects study. They received 9 stimulations of 20 s (3 non-nociceptive cold; 3 low nociceptive cold and 3 highly nociceptive cold) during a VRH session of 20 min (VRH condition) or without VRH (noVRH condition). Physiological monitoring during the cold pain stimulation protocol consisted of recording heart rate, heart rate variability and respiratory frequency. Maximum cold pain intensity perception, measured through the visual analog scale (VAS) on 10, was of 3.66 ± 1.84 (VAS score/10) in noVRH condition and 2.46 ± 1.54 in VRH (Wilcoxon, p < 0.0001). Considering pain unpleasantness perception, 3.68 ± 2.06 in noVRH and 2.21 ± 1.63 in VRH (Wilcoxon, p < 0.0001). Hypnotizability negatively correlated with the decrease in VAS intensity from noVRH to VRH (Spearman r = -0.45; p = 0.0038). In our sample, we found that 31/41 volunteers (75.6%) displayed a reduction of more than 10% of their VAS pain intensity and unpleasantness scores. Trait anxiety was the best predictor of the VRH responders, as well as heart rate variability. In addition, respiratory rate was diminished under VRH in every subgroup. VRH is an effective tool to reduced pain intensity and unpleasantness in a vast majority of healthy subjects. We further indicate in this study that heart rate variability parameter RMSSD (root mean square of successive differences) is a good predictor of this effect, as well as anxiety as a personality trait (but not state anxiety). Further studies are expected to determine more precisely to whom it will be the most useful to offer tailored, non-pharmacological pain management solutions to patients.

Pain-Related Stigma and Its Associations With Clinical and Experimental Pain Severity in Youth With Chronic Musculoskeletal Pain Conditions.

Many children with chronic musculoskeletal pain conditions experience stigma which can have negative downstream consequences. This study compares ratings of clinical pain (current pain intensity and pain interference), experimental pain (temporal summation, cold water tolerance, and cold pain intensity), and pain-related stigma among three groups of youth with rheumatic conditions. The relations among ratings of pain-related stigma and pain variables were explored. Eighty-eight youth aged 8-17 years with a diagnosis of juvenile idiopathic arthritis (JIA = 32), juvenile fibromyalgia (JFM = 31), or non-specific chronic pain (NSCP = 25) completed measures of clinical pain ratings (average 7-day pain intensity, day of assessment pain (DoA), and pain interference), experimental pain (cold pain tolerance, cold pain intensity, and temporal summation of mechanical pain), and pain-related stigma. Data analysis compared pain-related stigma and pain ratings across the three groups and examined the relations among pain-related stigma and pain ratings. Youth with JFM reported higher ratings of clinical pain and pain-related stigma than their counterparts with NSCP or JIA. However, there were no differences in experimental pain. Pain-related stigma was associated with greater ratings of pain interference, particularly for those with JIA and NSCP. Pain-related stigma was also associated with greater average daily pain intensity but not DoA. Youth with medically unexplained pain report greater stigma and worse pain than their peers; thus, robust assessment of pain in this population is necessary. Future work should longitudinally explore the impact of pain-related stigma on pain outcomes and treatment responses.

Manual Therapy Effects on Nonspecific Neck Pain Are Not Mediated by Mechanisms Related to Conditioned Pain Modulation: A Randomized Clinical Trial.

Manual therapy (MT) is a treatment recommended by clinical practice guidelines in the management of patients with neck pain. However, the mechanisms through which MT works remain unknown. The aim of the present study is to investigate if MT is mediated by mechanisms related to conditioned pain modulation (CPM), comparing the effects of painful with a pain-free MT treatment. A two-arm, parallel, randomized controlled clinical trial with concealed allocation and blinding of the outcome assessor was conducted in university students with chronic or recurrent nonspecific neck pain (NSNP). Participants received either a painful or pain-free MT session. Psychophysical variables including pressure pain thresholds, CPM, temporal summation of pain and cold pain intensity were assessed before and immediately after treatment. In addition, changes in neck pain intensity over the following 7 days and self-perceived improvement immediately and 7 days after treatment were assessed. No significant differences were found between groups in any of the psychophysical variables or in patients' self-perceived improvement. Only a significantly greater decrease in neck pain intensity immediately after treatment was found in the pain-free MT group compared to the painful MT group. The results suggest that the immediate and short-term effects of MT on NSNP are not mediated by CPM-related mechanisms.

Effects of High-Definition Transcranial Direct Current Stimulation Over the Primary Motor Cortex on Cold Pain Sensitivity Among Healthy Adults.

Some clinical studies have shown promising effects of transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) on pain relief. Nevertheless, a few studies reported no significant analgesic effects of tDCS, likely due to the complexity of clinical pain conditions. Human experimental pain models that utilize indices of pain in response to well-controlled noxious stimuli can avoid many confounds that are present in the clinical data. This study aimed to investigate the effects of high-definition tDCS (HD-tDCS) stimulation over M1 on sensitivity to experimental pain and assess whether these effects could be influenced by the pain-related cognitions and emotions. A randomized, double-blinded, crossover, and sham-controlled design was adopted. A total of 28 healthy participants received anodal, cathodal, or sham HD-tDCS over M1 (1 mA for 20 min) in different sessions, in which montage has the advantage of producing more focal stimulation. Using a cold pressor test, several indices reflecting the sensitivity to cold pain were measured immediately after HD-tDCS stimulation, such as cold pain threshold and tolerance and cold pain intensity and unpleasantness ratings. Results showed that only anodal HD-tDCS significantly increased cold pain threshold when compared with sham stimulation. Neither anodal nor cathodal HD-tDCS showed significant analgesic effects on cold pain tolerance, pain intensity, and unpleasantness ratings. Correlation analysis revealed that individuals that a had lower level of attentional bias to negative information benefited more from attenuating pain intensity rating induced by anodal HD-tDCS. Therefore, single-session anodal HD-tDCS modulates the sensory-discriminative aspect of pain perception as indexed by the increased pain threshold. In addition, the modulating effects of HD-tDCS on attenuating pain intensity to suprathreshold pain could be influenced by the participant’s negative attentional bias, which deserves to be taken into consideration in the clinical applications.

Cognitive agency in music interventions: Increased perceived control of music predicts increased pain tolerance.

Self-selected music is consistently found to be the strongest predictor for successful music listening interventions in pain management contexts, but the specific cognitive mechanisms that mediate these effects are currently unknown. The aim of this study was to isolate the role of cognitive agency on pain tolerance in music listening interventions, independently from parallel effects related to enjoyment. Additionally, the study examines the role of intramusical features and individual attributes related to musical engagement. Fifty-two participants completed a repeated measures experiment, which involved listening to six different pieces of music while completing the cold pressor task. Cognitive agency was operationalized by giving participants different degrees of perceived control over the music selection, when in fact it was pre-determined by the experimenter. A generalized linear mixed model was used to analyse the impact of perceived choice and intramusical features on pain tolerance measured in terms of duration on the cold pressor task, pain intensity and pain unpleasantness. Increased levels of perceived choice predicted increases in pain tolerance when enjoyment was accounted for. Individual levels of trait empathy and sophisticated emotional engagement with music also contributed to the effects. Intramusical features did not predict increases in pain tolerance. This study demonstrates that the reason self-selected music is particularly effective in reducing pain is related to the act of making a choice over the music itself. This study provides support for the cognitive vitality model and emphasizes the importance of giving people as much control as possible in music interventions. This study identifies that the act of selecting music contributes to increases in pain tolerance in parallel with the independent factor of enjoyment. This provides support for the role of cognitive agency in mediating the analgesic effects of music interventions, which suggests that people should be given as much control as possible in music interventions. Additionally, this study identifies specific individual attributes related to emotional engagement and empathy that amplify the effect of cognitive agency.

Efficacy of Anodal Suboccipital Direct Current Stimulation for Endogenous Pain Modulation and Tonic Thermal Pain Control in Healthy Participants: A Randomized Controlled Clinical Trial.

The aim of this study was to assess whether anodal DCS applied to the suboccipital (SO) target area could potentiate antinociception assessed primarily with conditioned pain modulation of tonic thermal test stimuli. Randomized double-blinded control trial. Rehabilitation hospital. Healthy participants. Forty healthy participants were randomized to receive either SO-DCS or M1-DCS. The 20-minute 1.5 mA anodal or sham DCS intervention were applied to each participant in randomized order during two test sessions. The primary outcome measure included heterotopic cold-pressor conditioned pain modulation (CPM) of tonic heat pain. Secondary measures included pressure pain threshold and tonic thermal pain intensity. Heterotopic CPM of tonic heat pain intensity was unaffected by either SO-DCS or active M1, including the secondary measures of pressure pain threshold and tonic thermal pain intensity. Although low-power non-significant interactions were identified for DCS intervention (active versus sham) and time (before and after), a significant within-group inhibition of tonic cold pain was identified following SO-DCS (P = .011, mean [SD]: -0.76 ± 0.88 points) and M1-DCS (P < .002: -0.84 ± 0.82 points), without a significant change following sham DCS. Although heterotopic CPM was not facilitated with either SO-DCS or M1-DCS, a general significant inhibition of tonic cold pain intensity was demonstrated following both interventions. The general effects of active DCS compared to sham on tonic cold pain-irrespective of the M1 or SO target-need to be confirmed using standard quantitative sensory testing.

A Personalized Spatial-Temporal Cold Pain Intensity Estimation Model Based on Facial Expression.

Objective: Pain assessment is of great importance in both clinical research and patient care. Facial expression analysis is becoming a key part of pain detection because it is convenient, automatic, and real-time. The aim of this study is to present a cold pain intensity estimation experiment, investigate the importance of the spatial-temporal information on facial expression based cold pain, and study the performance of the personalized model as well as the generalized model. Methods: A cold pain experiment was carried out and facial expressions from 29 subjects were extracted. Three different architectures (Inception V3, VGG-LSTM, and Convolutional LSTM) were used to estimate three intensities of cold pain: No pain, Moderate pain, and Severe Pain. Architectures with Sequential information were compared with single-frame architecture, showing the importance of spatial-temporal information on pain estimation. The performances of the personalized model and the generalized model were also compared. Results: A mean F1 score of 79.48% was achieved using Convolutional LSTM based on the personalized model. Conclusion: This study demonstrates the potential for the estimation of cold pain intensity from facial expression analysis and shows that the personalized spatial-temporal framework has better performance in cold pain intensity estimation. Significance: This cold pain intensity estimator could allow convenient, automatic, and real-time use to provide continuous objective pain intensity estimations of subjects and patients.

Pain threshold between men and women with different fat masses and percentages

BACKGROUND AND OBJECTIVES: There is a data gap regarding cold pain and pressure pain in healthy young individuals. The present study aimed to compare cold pain threshold and intensity and pressure threshold in young men and women with different fat percentages. METHODS: The study included 30 men and 42 women aged between 18 and 25 years, divided into two groups: normal - body mass index ≤24.9 and overweight - ≥25. Fat percentage was estimated by tetrapolar bioimpedance, pain-pressure threshold by pressure algometer, cold pain threshold was timed, and the intensity measured by the visual analog scale. RESULTS: The intensity of pain caused by cold showed no significant difference between groups, as well as the cold pain threshold and the initial and final pain threshold. The same behavior happened within the men and women groups. When comparing the difference between genders, pressure pain and cold pain thresholds had significant differences. Pain intensity did not differ between genders. CONCLUSION: Fat percentage did not affect the response time of cold pain and pressure pain thresholds and pain intensity in young adults. When considering gender, although the cold pain threshold in men was higher than in women, pain intensity was similar.

Correction: Predictors of opioid efficacy in patients with chronic pain: A prospective multicenter observational cohort study

[This corrects the article DOI: 10.1371/journal.pone.0171723.].

Longer Sleep Duration and Later Sleep Timing are Associated with Increased Cold-Pain Perception During the Day

Experimental studies on the associations between sleep and evoked pain in healthy individuals have generally demonstrated increased pain sensitivity following sleep deprivation, yet few have addressed the association between habitual sleep patterns and next-day pain sensitivity. This study aimed to assess relationships between habitual sleep quantity, quality, and timing based on objective measurement of sleep (actigraphy) and experimentally evoked cold-pain perception during the day in healthy young men. Forty-eight healthy, young male participants without pain or sleep disturbance were examined via cold pressor test to obtain measures of cold-pain threshold, tolerance, and intensity in the morning, afternoon, and evening, in a randomized-order repeated-measures design. Sleep characteristics were assessed by actigraphy for 7 days prior to testing. Correlations (Spearman) were computed between all sleep and pain measures. Sleep measures that significantly correlated with pain were entered as covariates in repeated-measures (RM) ANOVA. Longer sleep duration and later sleep timing were associated with increased sensitivity to evoked cold-pain tests at different times of the day (p < 0.05). After controlling for age, BMI, and weekday–weekend differences in sleep duration and bedtime, longer sleep duration, and later wake time were associated with lower pain threshold, and later bed- and wake times were associated with lower pain tolerance (p < 0.05). Sleep quality was not associated with any pain measures. Objectively measured habitual sleep duration and timing are associated with cold-pain perception in healthy young men. Further investigation is needed to elucidate the mechanism underlying the detrimental effects of long sleep duration and late sleep timing on pain perception.

Predictors of opioid efficacy in patients with chronic pain: A prospective multicenter observational cohort study.

Opioids are increasingly used for treatment of chronic pain. However, they are only effective in a subset of patients and have multiple side effects. Thus, studies using biomarkers for response are highly warranted. The current study prospectively examined 63 opioid-naïve patients initiating opioid use for diverse types of chronic pain at five European centers. Quantitative sensory testing, electroencephalography (EEG) recordings, and assessment of pain catastrophizing were performed prior to treatment. The co-primary outcomes were change from baseline in ratings of chronic pain and quality of life after 14 days of opioid treatment. Secondary outcomes included patient’s global impression of clinical change and side effects. Logistic regression models adjusted for age and sex were used to identify biomarkers predictive for successful treatment, defined as at least a 30% reduction in average pain intensity or an improvement in quality of life of at least 10 scale points. Fifty-nine patients (94%) completed the study. The mean age was 55 ± 16 years and 69% were females. Pain reduction was predicted by cold pain intensity (OR: 0.69; P = 0.01), pain catastrophizing (OR: 0.82; P = 0.03), relative delta (OR: 0.76; P = 0.03) and beta EEG activity (OR: 1.18; P = 0.04) induced by experimental cold pain. None of the study variables were related to improvement in quality of life. For the first time, individual pain processing characteristics have been linked to opioid response in a mixed chronic pain population. This has the potential to personalize treatment of chronic pain and restrict opioid use to patients with high likelihood for response.

Genetic variation in P2RX7 and pain

Abstract Background and aims P2X7 is a purinoceptor and non-selective cation channel that is activated by extracellular ATP, especially in immune and glia cells. Activation of P2X7 triggers the secretion of several pro-inflammatory substances, such as IL- 1P, IL-18, TNF-α, and nitric oxide. P2X7 activation contributes to the pro-inflammatory response to injury or bacterial invasion and mediates apoptosis. It has been implicated in physiological and pathological conditions such as bone tissue remodelling, inflammation, oncogenesis, depression, and inflammatory, neuropathic and chronic pain. Here, we aim to characterize the effects of variation within the P2RX7 gene, which encodes the P2X7 receptor, on pain and opioid requirements in human patients. Methods Pain was assessed in Norwegian and Finnish cohorts. The Norwegian cohort represents the 6th wave of the Tromsø Study, a longitudinal and cross-sectional population based study (N = 3700), whereas the Finnish cohort (BrePainGen) consists of patients who underwent breast cancer surgery (N = 1000). For both cohorts, experimental pain data were analyzed. Pain intensity and tolerance were assessed with cold pressor test and after standardized noxious heat stimulation in both cohorts. In addition, data on acute postoperative pain and opioid requirements were analyzed in the BrePainGen cohort. Postoperative pain and opioid responses were followed during 20 h after surgery. In total, 29 single nucleotide polymorphisms (SNPs) in P2RX7 were genotyped and their association with outcome variables was assessed using linear regression and analysis of variances (ANOVA). Results Several P2RX7 SNPs were associated with the pain phenotypes. The strongest associations were seen with cold pain intensity and tolerance. The results of this study will be presented at the meeting. Conclusions Our results suggest that P2X7 and genetic varia-tion in the P2RX7-gene are involved in the modulation of human pain responses.

Maternal Anxiety and Children's Laboratory Pain: The Mediating Role of Solicitousness.

There has been limited empirical examination of how parent variables such as anxiety and solicitousness collectively impact child pain response. We sought to examine the relationships among maternal anxiety, solicitous parenting, and children’s laboratory anxiety and pain intensity in children with chronic pain. Participants included 80 children and adolescents (ages 8–18) with chronic pain and their mothers. Children completed questionnaires and lab pain tasks measuring their parents’ solicitous parenting, pressure, cold and heat pain anticipatory anxiety and pain intensity. Using bootstrapping analysis, maternal anxiety predicted child anticipatory anxiety and pain intensity in girls with chronic pain, which was mediated by the child’s report of parental solicitousness. For boys with chronic pain, maternal anxiety predicted boys’ anticipatory anxiety and pain intensity, with no support for mediation. This study adds to the growing literature demonstrating the impact of maternal anxiety on children’s pain. The study highlights the importance of considering parents in treatment designed to reduce children’s pain.

Quantitative and Qualitative Responses to Topical Cold in Healthy Caucasians Show Variance between Individuals but High Test-Retest Reliability.

Increased sensitivity to cold may be a predictor of persistent pain, but cold pain threshold is often viewed as unreliable. This study aimed to determine the within-subject reliability and between-subject variance of cold response, measured comprehensively as cold pain threshold plus pain intensity and sensation quality at threshold. A test-retest design was used over three sessions, one day apart. Response to cold was assessed at four sites (thenar eminence, volar forearm, tibialis anterior, plantar foot). Cold pain threshold was measured using a Medoc thermode and standard method of limits. Intensity of pain at threshold was rated using a 10cm visual analogue scale. Quality of sensation at threshold was quantified with indices calculated from subjects' selection of descriptors from a standard McGill Pain Questionnaire. Within-subject reliability for each measure was calculated with intra-class correlation coefficients and between-subject variance was evaluated as group coefficient of variation percentage (CV%). Gender and site comparisons were also made. Forty-five healthy adults participated: 20 male, 25 female; mean age 29 (range 18–56) years. All measures at all four test sites showed high within-subject reliability: cold pain thresholds r = 0.92–0.95; pain rating r = 0.93–0.97; McGill pain quality indices r = 0.87–0.85. In contrast, all measures showed wide between-subject variance (CV% between 51.4% and 92.5%). Upper limb sites were consistently more sensitive than lower limb sites, but equally reliable. Females showed elevated cold pain thresholds, although similar pain intensity and quality to males. Females were also more reliable and showed lower variance for all measures. Thus, although there was clear population variation, response to cold for healthy individuals was found to be highly reliable, whether measured as pain threshold, pain intensity or sensation quality. A comprehensive approach to cold response testing therefore may add validity and improve acceptance of this potentially important pain measure.

Effect of endocannabinoid degradation on pain: role of FAAH polymorphisms in experimental and postoperative pain in women treated for breast cancer.

Fatty acid amide hydrolase (FAAH) metabolizes the endocannabinoid anandamide, which has an important role in nociception. We investigated the role of common FAAH single-nucleotide polymorphisms (SNPs) in experimentally induced and postoperative pain. One thousand women undergoing surgery for breast cancer participated in the study. They were tested for cold (n = 900) and heat pain (n = 1000) sensitivity. After surgery, their pain intensities and analgesic consumption were carefully registered. FAAH genotyping was performed using MassARRAY platform and genome-wide chip (n = 926). Association between 8 FAAH SNPs and 9 pain phenotypes was analyzed using linear regression models. The results showed that carrying 2 copies of a missense variant converting proline at position 129 to threonine (rs324420) resulted in significantly lower cold pain sensitivity and less need for postoperative analgesia. More specifically, rs324420 and another highly correlated SNP, rs1571138, associated significantly with cold pain intensity (corrected P value, 0.0014; recessive model). Patients homozygous for the minor allele (AA genotype) were less sensitive to cold pain (β = -1.48; 95% CI, -2.14 to -0.8). Two other SNPs (rs3766246 and rs4660928) showed nominal association with cold pain, and SNPs rs4141964, rs3766246, rs324420, and rs1571138 nominal association with oxycodone consumption. In conclusion, FAAH gene variation was shown to associate with cold pain sensitivity with P129T/rs324420 being the most likely causal variant as it is known to reduce the FAAH enzyme activity. The same variant showed nominal association with postoperative oxycodone consumption. Our conclusions are, however, limited by the lack of replication and the results should be replicated in an independent cohort.

Pain Perception in Healthy Young Men Is Modified by Time-Of-Day and Is Modality Dependent

Several physiological processes exhibit 24-hour oscillations termed circadian rhythms. Despite numerous investigations on the circadian dynamics of pain perception, findings related to this issue remain inconsistent. This study aimed to assess the effect of time-of-day on multimodal experimental pain perception in healthy males, including "static" and "dynamic" quantitative sensory tests. A random order tests were performed in the morning, afternoon and evening. Forty-eight healthy males (25.9 ± 4.7 years old). Three different pain modalities i) mechanical (pain threshold, tolerance, and intensity), ii) heat (pain threshold and intensity), iii) cold (pain threshold measured in °C and in seconds and cold pain tolerance and intensity) utilizing nine "static" pain parameters, and two "dynamic" pain paradigms i) temporal summation and ii) conditioned pain modulation were assessed in each session. Pain scores varied significantly in six pain parameters during the day. Specifically, lower pain scores were found in the morning for cold pain threshold (in seconds and in °C), cold pain intensity, cold pain tolerance, heat pain threshold and intensity. There were no significant diurnal differences in the mechanical evoked pain parameters or in either of the "dynamic" pain paradigms. Thermal pain scores varies during the day and morning seems to be the time-of-day most insensitive to pain. Also, dynamic tests and the mechanical pain model are not appropriate for detecting diurnal variability in pain. The results of this study may be partially explained by a potential analgesic effect of some hormones known to have diurnal variation (e.g., melatonin and cortisol).

Influence of different frequencies of transcutaneous electrical nerve stimulation on the threshold and pain intensity in young subjects.

Objective To investigate the effects of different transcutaneous electrical nerve stimulation frequencies in nociception front of a pressure pain threshold and cold in healthy individuals.Methods Twenty healthy subjects were divided into four groups, all of which have gone through all forms of electrical stimulation at different weeks.Assessments were pre and post-therapy, 20 and 60 minutes after stimulation. To evaluate the pressure pain threshold, an algometer was used with one tapered tip, pressing the hypothenar region until voluntary report the word “pain”. Cold pain intensity was assessed by immersion in water at 5°C for 30 seconds; at the end, the subject was asked to quantify the pain intensity on a Visual Analog Scale for Pain. For electrical stimulation, two electrodes were used near the elbow, for 20 minutes, with an intensity strong, but not painful. The frequency was in accordance with the group: 0Hz (placebo); 7Hz; 100Hz; and 255Hz.Results Both for the assessment of pressure pain threshold as the cold pain intensity, there was no significant difference (p>0.05).Conclusion We conclude that the use of transcutaneous electrical nerve stimulation on dermatomes C6 to C8 produced no significant change in pressure pain threshold or cold discomfort.

Opioid-Induced Hyperalgesia (OIH): A Real Clinical Problem or Just an Experimental Phenomenon?

Although opioid-induced hyperalgesia (OIH) is mentioned as a potential cause of opioid dose escalation without adequate analgesia, true evidence in support of this notion is relatively limited. Most studies conducted in the context of acute and experimental pain, which seemingly demonstrated evidence for OIH, actually might have measured other phenomena such as acute opioid withdrawal or tolerance. OIH studies in patients with chronic pain have used various experimental pain models (such as cold pain tolerance or heat pain intensity). Therefore, the fact that they have yielded inconsistent results is hard to interpret. Thus far, with the exception of a few clinical case reports on OIH in patients with cancer pain and one prospective study in patients with chronic neuropathic pain, evidence for OIH in patients with chronic or cancer-related pain is lacking. Whether experimental pain models are necessary for establishing the clinical diagnosis of OIH, and which specific model is preferred, are yet to be determined.