Magnitude Of Conditioned Pain Modulation Research Articles

Exploring the sex differences in conditioned pain modulation and its biobehavioral determinants in healthy adults

BackgroundFemales are at greater risk of chronic pain, and exhibit higher pain sensitivity compared to males. However, sex differences in conditioned pain modulation (CPM), a neurophysiological risk factor of chronic pain, are unclear. CPM is influenced by many factors, some of which are sex-dependent. This study explored the sex differences in CPM and its biobehavioral determinants, such as blood pressure responses, physical activity levels, pain catastrophizing scores, and conditioning stimulus intensity, in young, healthy, physically active males and females. MethodsTwenty-six males and 24 females completed the CPM test using an electrical pain stimulus and a cold pain stimulus induced via 2 min of cold pressor test. Blood pressure was assessed at baseline and during cold pressor test, whereas cold pain ratings were obtained during cold pressor test to monitor the conditioning stimulus intensity. Physical activity was evaluated via questionnaires and accelerometer, whereas pain catastrophizing was evaluated via a questionnaire. ResultsBoth males and females exhibited CPM, without sex differences in the magnitude of CPM. The males showed higher resting blood pressure, higher physical activity levels, and lower pain catastrophizing scores than the females, without sex differences observed in cold pain ratings and proportion of those who met the physical activity guidelines. No correlations were observed between CPM and its determinants. ConclusionsThe results suggest the complexity of mechanisms underlying the sex differences in CPM. The sex differences in CPM, along with its determinants, may need to be examined in individuals with some risk factors for chronic pain.

Conditioned pain modulation and offset analgesia: Influence of sex, sex hormone levels and menstrual cycle on the magnitude and retest reliability in healthy participants.

Conditioned pain modulation (CPM) and offset analgesia quantify impairment of endogenous pain modulation, but magnitude and reliability vary broadly between studies, indicating influencing factors that are not currently controlled for. The aim of this study was to quantify magnitude and retest reliability of CPM and offset analgesia in healthy participants, while investigating the influence of sex and sex hormone levels. Sixty-two participants (30 female) completed the study. We tested CPM (heat-cold paradigm) and offset analgesia on 6 days within two menstrual cycles (tests were performed in each phase of two subsequent menstrual cycles, with similar time points for men). Median offset effect was -29.4% in female and - 22.5% in male participants (as change from initial stimulus). Median early CPM effects were - 16.7% for women versus -13.3% for men. Reliability (intra-class correlation coefficient [ICC]) was similar between the main measures, offset effect (female: 0.48, male: 0.47) and early CPM effect (female: 0.49, male: 0.43). There was significant variance between individual experimental parameters within protocols but not between sexes or menstrual phases. While oestradiol and progesterone did not correlate with the magnitude of effect within sexes, we found that testosterone levels explained an estimated 5%-10% of variance within individual responses in all sexes. Our results show that the reliability of both CPM effect and offset analgesia was independent of sex and menstrual cycle phase. The magnitude of CPM and offset effects was weakly influenced by sex and testosterone levels, indicating an area for future research, rather than clinical significance. This study investigated CPM and offset analgesia in parallel, across sexes and during two menstrual cycles while assessing the impact of sex hormones. Reliability seems to depend on experimental parameters rather than participant characteristics, while the magnitude of effect could be weakly linked to sex hormones and sex.

The Contribution of Psychological Factors to Inter-Individual Variability in Conditioned Pain Modulation Is Limited in Young Healthy Subjects.

Conditioned pain modulation (CPM) describes the decrease in pain perception of a test stimulus (TS) when presented together with a heterotopic painful conditioning stimulus (CS). Inter-individual differences in CPM are large and have been suggested to reflect differences in endogenous pain modulation. In a previous analysis, we demonstrated that in young, healthy participants, inter-individual differences account for about one-third of CPM variance, with age and sex together explaining only 1%. Here, we investigated if psychological factors explain significant amounts of inter-individual variance in CPM. Using the same dataset as before, we performed both cross-sectional (n = 126) and repeated measures (n = 52, 118 observations) analysis and the corresponding variance decompositions, using results of psychological questionnaires assessing depression, trait anxiety and pain catastrophizing. Psychological factors did not significantly predict CPM magnitude, neither directly nor when interactions with the CPM paradigm were assessed; however, the interaction between depression and the paradigm approached significance. Variance decomposition showed that the interaction between depression and the CPM paradigm explained an appreciable amount of variance (3.0%), but this proportion seems small when compared to the residual inter-individual differences (35.4%). The main effects of the psychological factors and the interactions of anxiety or catastrophizing with the CPM paradigm are explained at <0.1% each. These results show that the contribution of psychological factors to inter-individual CPM differences in healthy participants is limited and that the large inter-individual variability in the CPM effect remains largely unexplained.

Test-retest reliability of pressure pain threshold and heat pain threshold as test stimuli for evaluation of conditioned pain modulation

ObjectivesThere is growing interest in conditioned pain modulation (CPM) protocols for evaluating the function of the descending pain-modulatory system in clinical settings. The aim of this study was to evaluate test-retest reliability of a CPM protocol with contact heat as a conditioning stimulus (CS) and two test stimuli (pressure pain threshold (PPT) and heat pain threshold (HPT)), all applied within one session. In addition, gender and age differences were evaluated. MethodsThe study included 87 healthy subjects (average age 37.95 ± 12.02 years, 57.5% females). The magnitude of the results of the CPM test was calculated as the difference between subject-reported pain thresholds before and after application of the CS. To assess the reliability of the protocol, a subgroup of 66 subjects underwent re-test after 14±1 days. In order to investigate the influence of age on the CPM magnitude, subjects were divided into subgroups (20–29, 30–39, 40–49, 50–59 years). ResultsThe pain thresholds for both test stimuli (TS) were significantly higher following the application of the CS (p < 0.001). Values of the interclass correlation coefficient (ICC) for the CPM with PPT as the TS indicated good reliability (ICC=0.631, 95% CI:0.365–0.782), while those for the HPT indicated poor reliability (ICC=0.328, 95% CI:-0.067–0.582). Significant differences in CPM between genders were found for both TS. Significant CPM differences were not detected among the four age subgroups for either TS. ConclusionsCPM effects can be successfully induced with both PPT and HPT as a TS, but PPT showed significantly higher reliability.

Effects of acute mental stress on conditioned pain modulation in temporomandibular disorders patients and healthy individuals.

Stress is a contributing factor to painful temporomandibular disorders (TMD). Nevertheless, the underpinnings of this relationship are not fully understood. Objective To investigate the effects of acute mental stress on conditioned pain modulation (CPM) in TMD patients compared with healthy individuals.Methodology Twenty women with chronic myofascial TMD diagnosed according to the RDC/TMD and 20 age-matched healthy women had the CPM assessed before and after a stressful task using the Paced Auditory Serial Addition Task (PASAT) in a single session. Subjective stress response was assessed with the aid of visual analog scale (VAS). Pressure pain threshold (PPT) on masseter muscle was the test stimulus (TS) and immersion of the participant’s hand on hot water was the conditioning stimulus (CS) - CPM-sequential paradigm.Results Healthy individuals reported PASAT are more stressful when compared with TMD patients and the stress task did not affect the CPM in neither group. Nonetheless, a negative correlation was observed between change in CPM and change in TS from baseline to post-stress session, which indicates that the greater the increase in PPT after the stress task, the greater was the decrease in CPM magnitude. The correlation was strong for healthy controls (r=- 0.72, p<0.001) and moderate for TMD patients (r=- 0.44, p=0.047).Conclusions The correlation between the change in CPM and the TS change following the stress task may possibly indicate an overlapping pathway between stress-induced analgesia/hyperalgesia and descending pain inhibition.

The effect of mindful attention training for pain modulation capacity: Exploring the mindfulness-pain link.

Mindfulness has been shown to be beneficial for chronic pain. The underlying mechanisms of the mindfulness-pain link, however, are yet to be established. Particularly, the effects of mindfulness on pain modulation, which is shown to be dysfunctional among chronic pain patients, barely has been tested. This study investigated whether a short mindful attention training based on Langerian mindfulness mitigates reductions in pain modulation. Systemic quantitative-somatosensory testing of conditioned pain modulation (CPM) was conducted in 60 undergraduates, who were randomly assigned to one of three groups: (1) Pain-specific mindful attention training; (2) nonspecific mindful attention training; and (3) no mindful attention training. CPM was tested before and after the intervention. As hypothesized, a reduction in CPM magnitude was observed only in the control group, whereas this reduction was abolished in the two mindfulness groups. Langerian mindfulness may mitigate pain modulation reduction as observed in chronic pain, thus shedding light on its potential advantages.

The role of itch and pain modulation in the prediction of phototherapy outcomes: a prospective cohort study

Objectives Ability to predict which chronic itch patients will benefit from particular treatments is a challenge. Common features in itch and pain in respect to sensory elicitation, and mechanisms of processing including sensitization and inhibition at the peripheral and central levels, may serve to understand variability in treatment outcomes. As such this study aimed to explore whether phototherapy outcomes can be predicted by psychophysical parameters of pain and itch modulatory processing. Methods Prospective cohort study on chronic-itch patients (n = 44) assessed before 20 treatments of NB UVB. Level of itch and pain reduction following painful stimulation (reflecting the ‘pain inhibits pain’ phenomenon) used to assess the top-down modulation response efficacy. Magnitude of Conditioned Pain Modulation (CPM) for itch (CPM-itch) and for pain (CPM-pain) (reflecting inhibition) and magnitude of temporal summation (TS) of pain (reflecting ascending facilitation pathways) assessed to predict treatment effect. Results Higher improvement of itch symptoms following phototherapy was correlated with more efficient CPM-itch (r = 0.62, p < .001), but not magnitude of CPM-pain or level of temporal summation. Discussion Findings emphasize the role of descending inhibition pathways in determining phototherapy efficacy in chronic itch patients. Such an evaluation-based approach may contribute to better patient selection for phototherapy improving patients’ disease outcomes.

Conditioned Pain Modulation And Blood Pressure Responses To Cold Pressor Test Among Resistance Exercisers

Conditioned pain modulation (CPM) examines central pain inhibitory processing by assessing changes of sensitivity to the first pain stimulus after exposure to the second pain stimulus compared to baseline, and serves as risk factor of chronic pain. Aerobically-trained individuals typically show greater CPM compared to controls, but little is known regarding CPM among resistance exercisers (REs) who habitually engage in resistance exercise/strength training. REs often show elevated resting blood pressure (BP), which is associated with greater BP responses to cold pressor test (CPT) of immersing a hand into a cold water bath. Given past research showing the positive association between CPM and BP responses to CPT as the second pain stimulus, REs may exhibit greater CPM, along with augmented BP responses to CPT. PURPOSE: To compare CPM and BP responses to CPT between REs and controls. METHODS: REs were primarily recruited from weight lifting and power lifting teams (n = 15). Controls were healthy, normally active individuals (NAs) (n = 15). The participants completed the CPM test to evaluate changes in pain ratings (0-100) to electrical stimuli delivered to the ankle after CPT for a maximum of 2 minutes compared to baseline. The magnitude of CPM was calculated as change scores: post-CPT pain ratings - baseline pain ratings, with smaller pain ratings indicating greater pain inhibition. BP was assessed at baseline and every minute during CPT. CPM and BP data were analyzed using a mixed model ANOVA. The relationship between CPM and BP was tested using a correlational analysis. RESULTS: Each group consisted of young, 9 men and 6 women (REs: 23 ± 5 yrs vs. NAs: 22 ± 2 yrs, p > 0.05). REs reported spending 9.1 ± 4.5 hours/week for resistance exercise. REs and NAs exhibited comparable CPM (Change scores. REs: -12 ± 12 vs. NAs: -14 ± 12, p > 0.05), but REs showed greater systolic BP responses to CPT compared to NAs (Mean SBP. REs: 129 ± 11 mmHg vs. NAs: 119 ± 14 mmHg, p < 0.05). No significant association was found between systolic BP and CPM in REs (Resting: r = 0.2, p > 0.05 & Reactivity: r = -0.2, p > 0.05), but resting systolic BP was positively associated with CPM in NAs (Resting: r = 0.5, p < 0.05 & Reactivity: r = -0.1, p > 0.05). CONCLUSION: The role of BP in CPM is likely complex, and the potential role of exercise in central pain processing needs to be studied.

Reliability of the conditioned pain modulation paradigm across three anatomical sites.

Background and aims Conditioned Pain Modulation (CPM) is a measure of pain inhibition-facilitation in humans that may elucidate pain mechanisms and potentially serve as a diagnostic test. In laboratory settings, the difference between two pain measures [painful test stimulus (TS) without and with the conditioning stimulus (CS) application] reflects the CPM magnitude. Before the CPM test can be used as a diagnostic tool, its reliability on the same day (intra-session) and across multiple days (inter-session) needs to be known. Furthermore, it is important to determine the most reliable anatomical sites for both the TS and the CS. This study aimed to measure the intra-session and inter-session reliability of the CPM test paradigm in healthy subjects with the TS (pressure pain threshold-PPT) applied to three test sites: the face, hand, and dorsum of the foot, and the CS (cold pressor test-CPT) applied to the contralateral hand. Methods Sixty healthy participants aged 18-65 were tested by the same examiner on 3 separate days, with an interval of 2-7 days. On each day, testing was comprised of two identical experimental sessions in which the PPT test was performed on each of the three dominant anatomical sites in randomized order followed by the CPM test (repeating the PPT with CPT on the non-dominant hand). CPM magnitude was calculated as the percent change in PPT. The Intraclass Correlation Coefficient (ICC), Coefficient of Variation (CV), and Bland-Altman analyses were used to assess reliability. Results PPT relative reliability ranged from good to excellent at all three sites; the hand showed an intra-session ICC of 0.90 (0.84, 0.94) before CPT and ICC of 0.89 (0.83, 0.92) during CPT. The PPT absolute reliability was also high, showing a low bias and small variability when performed on all three sites; for example, CV of the hand intra-session was 8.0 before CPT and 8.1 during CPT. The relative reliability of the CPM test, although only fair, was most reliable when performed during the intra-session visits on the hand; ICC of 0.57 (0.37, 0.71) vs. 0.20 (0.03, 0.39) for the face, and 0.22 (0.01, 0.46) for the foot. The inter-session reliability was lower in all three anatomical sites, with the best reliability on the hand with an ICC of 0.40 (0.23, 0.55). The pattern of absolute reliability of CPM was similar to the relative reliability findings, with the reliability best on the hand, showing lower intra-session and inter-session variability (CV% = 43.5 and 51.5, vs. 70.1 and 73.1 for the face, and 75.9 and 78.9 for the foot). The CPM test was more reliable in women than in men, and in older vs. younger participants. Discussion The CPM test was most reliable when the TS was applied to the dominant hand and CS performed on the contralateral hand. These data indicate that using the CS and TS in the same but contralateral dermatome in CPM testing may create the most reliable results.

Enhanced pain modulation capacity among individuals with borderline personality disorder: A possible mechanism underlying their hypoalgesia.

Ample evidence suggests that individuals with borderline personality disorder (BPD) exhibit hyposensitivity to pain. Since the underlying mechanism of the pain hyposensitivity is unknown, we tested here for the first time whether this hyposensitivity is pain specific or exists also for innocuous sensation, and whether it is associated with enhanced descending pain modulation capabilities. Participants were 55 women; 22 patients with BPD and 33 matched healthy controls. Testing included the measurement of warmth sensation threshold (WST), heat-pain threshold (HPT), pain adaptation, conditioned pain modulation (CPM) and temporal summation of heat-pain (TSP). The level of dissociation was also evaluated. Women with BPD had higher WST and HPT compared with healthy controls. Moreover, women with BPD had greater magnitude of pain adaptation and CPM as well as higher dissociation level compared to controls. In neither the BPD nor the control group did WST and HPT correlate with pain adaptation, CPM or dissociation. In the BPD group only, HPT inversely correlated with the magnitude of TSP. Women with BPD present generalized hyposensitivity to both innocuous and noxious stimuli. Furthermore, women with BPD exhibit more efficient pain inhibition capabilities than healthy controls. While efficient pain modulation may underlie pain hyposensitivity in BPD, both traits may exist independently from each other, or may be moderated by another factor such as dissociation. On the basis of testing pronociceptive and antinociceptive components among individuals with BPD and healthy controls, this study reveals enhanced ability to inhibit pain among woman with borderline personality disorder (BPD) which may underlie hyposensitivity to both noxious and innocuous stimuli and perhaps also self-injurious behaviour among these individuals. The study contributes novel information on possible mechanisms involved in BPD manifestations.

Biomarkers for predicting central neuropathic pain occurrence and severity after spinal cord injury: results of a long-term longitudinal study.

Central neuropathic pain (CNP) after spinal cord injury (SCI) is debilitating and immensely impacts the individual. Central neuropathic pain is relatively resistant to treatment administered after it develops, perhaps owing to irreversible pathological processes. Although preemptive treatment may overcome this shortcoming, its administration necessitates screening patients with clinically relevant biomarkers that could predict CNP early post-SCI. The aim was to search for such biomarkers by measuring pronociceptive and for the first time, antinociceptive indices early post-SCI. Participants were 47 patients with acute SCI and 20 healthy controls. Pain adaptation, conditioned pain modulation (CPM), pain temporal summation, wind-up pain, and allodynia were measured above, at, and below the injury level, at 1.5 months after SCI. Healthy control were tested at corresponding regions. Spinal cord injury patients were monitored for CNP emergence and characteristics at 3 to 4, 6 to 7, and 24 months post-SCI. Central neuropathic pain prevalence was 57.4%. Central neuropathic pain severity, quality, and aggravating factors but not location somewhat changed over 24 months. Spinal cord injury patients who eventually developed CNP exhibited early, reduced at-level pain adaptation and CPM magnitudes than those who did not. The best predictor for CNP emergence at 3 to 4 and 7 to 8 months was at-level pain adaptation with odds ratios of 3.17 and 2.83, respectively (∼77% probability) and a cutoff value with 90% sensitivity. Allodynia and at-level CPM predicted CNP severity at 3 to 4 and 24 months, respectively. Reduced pain inhibition capacity precedes, and may lead to CNP. At-level pain adaptation is an early CNP biomarker with which individuals at risk can be identified to initiate preemptive treatment.

Pain inhibitory mechanisms and response to weak analgesics in patients with knee osteoarthritis.

Conditioned pain modulation (CPM) and offset analgesia are different features of descending pain inhibition. This study investigated CPM, offset analgesia and clinical pain measures in patients with knee osteoarthritis (KOA) before and after treatment with the combination of a non-steroidal anti-inflammatory drug (NSAIDs) plus acetaminophen. Forty-two patients with KOA received Ibuprofen 1.2g/daily and acetaminophen 3.0g/daily for three weeks. Before administration, CPM magnitude was assessed as the difference between cuff pain detection (cPDT) with and without a conditioning stimulus (evoked by tourniquet pain). Offset analgesia was assessed as the pain intensities evoked by a constant 46°C for 30-s stimulus compared to an offset analgesia paradigm of 46°C for 5-s, 47°C for 5-s and 46°C for 20-s. The worst pain within the last 24-hr and pain during activity were assessed before and after treatment. Clinical pain significantly decreased after treatment (p<0.001) and less efficient CPM before treatment was associated with weaker analgesic effect (R=0.354, p=0.043). No significant modulation of CPM or offset analgesia was found for the treatment. This study found that less efficient CPM is associated with reduced analgesic effect of NSAIDs plus acetaminophen in patients with KOA whereas the treatment did not modulate CPM nor offset analgesia magnitude. This study demonstrated that conditioned pain modulation is correlated with the response to a standard pharmaceutical interventions treating osteoarthritis pain. Furthermore, we demonstrated that a decrease in clinical pain intensity is not associated with a normalization of conditioned pain modulation or offset analgesia, which questions if restoring these descending pain inhibitory mechanisms are pain intensity driven.

Recurrent low back pain patients demonstrate facilitated pronociceptive mechanisms when in pain, and impaired antinociceptive mechanisms with and without pain.

Low back pain (LBP) has been inconsistently associated with enhanced pronociceptive and impaired antinociceptive mechanisms. It remains unknown whether alterations are causal, consequential, or coincidental to pain presence. This study investigated pronociceptive and antinociceptive mechanisms in recurrent LBP (RLBP) patients across painful and pain-free periods, compared with age/sex-matched asymptomatic controls. During a painful episode (day 0) and when pain-free (day 28), 30 RLBP patients were assessed and compared with 30 controls over the same timeframe. Pressure pain thresholds were recorded bilaterally on the arm, back, and leg. Cuff algometry was used to assess cuff pressure pain detection threshold and cuff pain tolerance threshold on the lower legs, as well as temporal summation of pain (10 repeated painful cuff test stimuli on the dominant leg scored on a visual analogue scale) and conditioned pain modulation ([CPM]: cuff pain detection/tolerance threshold on dominant leg, before vs during painful cuff conditioning on the contralateral leg). Recurrent LBP patients displayed reduced pressure pain thresholds at the arm and back on day 0 compared with day 28 (P < 0.047) and with controls on day 0 (P < 0.049). Cuff pain detection threshold was reduced, and ratings of suprathreshold test stimuli were increased in RLBP patients on day 0 compared with day 28 (P < 0.02). Temporal summation of pain magnitude (increase in visual analogue scale scores) was enhanced in RLBP participants on day 0 compared with day 28 (P = 0.027) and with controls on day 0 (P = 0.039). Conditioned pain modulation magnitude (increased threshold during conditioning) was lower overall in RLBP participants than in controls (P = 0.021). Enhanced pronociceptive mechanisms were observed in RLBP patients. When pain-free, measures returned to similar levels as controls, except for CPM, which remained impaired.

The relationship between sensitivity to pain and conditioned pain modulation in healthy people

BackgroundThe relationship between sensitivity to pain and conditioned pain modulation (CPM) – a paradigm reflecting the activity of the endogenous descending analgesic system - is still unclear. This study aimed at investigating CPM magnitude in two distinct subgroups of healthy subjects, presenting low vs. high sensitivity to pain (LSP vs. HSP, respectively), by employing two different thermal paradigms of CPM. MethodNinety-five healthy subjects (out of 293 tested) were identified as LSP (n = 48) or HSP (n = 47) according to their tolerance time to noxious cold stimulation (Cold Pressor Test, 1 °C). All subjects were exposed to two different paradigms of CPM: 1) Fixed temperature ‘test-pain’ (TP) where phasic, fixed painful heat stimuli of 47 °C were administered before and during a prolonged ‘conditioning stimulus’ (cold water at 12 °C for 30 s); and 2) Individually based 'pain-60' where TP was determined as the temperature that induced pain at a magnitude of 60 on a 0–100 rating scale (with the same conditioning stimulus). ResultUsing both thermal paradigms, LSP subjects showed decreased CPM magnitudes in comparison to HSP (p < 0.0001 in both paradigms). Within each group, no differences in the magnitudes of CPM were found between the two paradigms. ConclusionThese findings show that regardless of the thermal CPM paradigm employed, healthy individuals exhibiting low sensitivity to pain have a low pain inhibition profile and vice-versa. It is suggested that in healthy subjects, pain sensitivity predisposes the magnitude of CPM and not the other way around.

(158) Responders and Non-Responders of Conditioned Pain Modulation May Depend On Testing Site and Repeated Measurement

Conditioned pain modulation (CPM) measures the efficiency of endogenous pain inhibition and is regarded as a systemic effect. It is unknown, whether individuals respond to CPM similarly between test sites and the effect of repeated measurements. The aim of this study was to investigate within individuals 1) whether CPM magnitude is consistent between test sites within the same CPM trial, 2) whether CPM responders and non-responders are similar between test sites, and 3) if these relations change with repeated measurement (within and between sessions). Twenty subjects (19.9±1.3 years; 10 females) participated in three experimental sessions separated by approximately one week. CPM was measured 4 times; once in the first and third sessions and twice in the second session (separated by 45-minutes of quiet rest). CPM was measured as the percent change in pressure pain thresholds at the right quadriceps and deltoid muscles (test stimuli) before and during ice-water immersion (conditioning stimulus; 6±0.5°C; 2-minute duration) of the left foot. Intraclass correlations (ICCs(2,k)) were computed between assessment sites in each CPM trial. CPM responders at each assessment site were determined based on a change greater than the standard error of measurement of each assessment site. Cohen's Kappa was computed to determine the level of agreement between the sites in each CPM trial. In the first and third sessions, there was good agreement in CPM magnitude between assessment sites (ICC first session=0.611 [0.008-0.847]; ICC third session=0.535 [-0.093-0.810]) but poor agreement in responders vs. non-responders (κ first session=-0.053; κ third session=-0.098). During the second session, agreement in both CPM trials improved between the sites in terms of magnitude (ICC first trial=0.878 [0.694-0.952]; ICC second trial=0.867 [0.669-0.947]) and responders/non-responders (κ first trial=-0.762; κ second trial=-0.375). The site of the test stimulus may produce opposite outcomes and influence how endogenous pain inhibition is interpreted.

(179) Repeated Exposure to Conditioned Pain Modulation Reduces Situational Pain Catastrophizing to the Conditioning Stimulus

The Situational Pain Catastrophizing Scale (S-PCS) measures an individual's negative mental set in reference to an ongoing or recent painful experience. It is not known whether the relation of S-PCS to conditioned pain modulation (CPM) changes with repeated exposure. The aim of this study was to examine changes in S-PCS relative to the conditioning stimulus and its relation to the magnitude of CPM both within and between study sessions. Twenty subjects (19.9±1.3 years; 10 females) participated in three experimental sessions. CPM was measured once in the first and third sessions, and twice in the second session (separated by 45 minutes of quiet rest). CPM was measured as the relative change in pressure pain thresholds at the right quadriceps and deltoid muscles (test stimuli) before and during ice water immersion (conditioning stimulus; 6±0.5°C; 2-minute duration) of the left foot. Pain ratings of the left foot were reported using a numerical pain rating scale at 20 seconds and the end of the conditioning stimulus. S-PCS was completed following each CPM protocol in reference to the conditioning stimulus. Relative CPM magnitude was similar across sessions and between sites (p>0.05). Pain intensity during the ice water immersion at 20 seconds (4.08±1.9/10) and at the end (5.4±2.1/10) was similar across all CPM protocols (p>0.05). S-PCS decreased significantly across all three sessions (8.30, 6.65, 5.10/24; p 0.05). No correlation was found between subjects’ S-PCS scores and magnitude of CPM in all the trials (p>0.05); however, there was a correlation between S-PCS and reported foot pain at the end (r=0.48; p

Endogenous Pain Modulation Profiles Among Individuals With Chronic Pain: Relation to Opioid Use

It is generally assumed that individuals exhibiting high pain inhibition also tend to exhibit low pain facilitation, but little research has examined this association in individuals with pain. The aims of this cross-sectional study were 1) to examine the association between measures of conditioned pain modulation (CPM) and temporal summation (TS) in individuals with chronic pain, and 2) to examine whether this association was moderated by demographic (age, sex), psychological (depression, catastrophizing), or medication-related (opioid use) variables. Individuals (N= 190) with back or neck pain completed questionnaires and underwent a series of quantitative sensory testing procedures assessing CPM and TS. Results indicated that individuals with higher levels of CPM showed lower levels of TS, r = –.20, P < .01. Analyses, however, revealed that the magnitude of this association was substantially weaker among opioid users (r= –.08, NS) than nonusers (r= −.34, P < .01). None of the demographic or psychological variables included in our study influenced the association between CPM and TS. The magnitude of CPM was lower for opioid users than nonusers, suggesting that opioid use might dampen the functioning of endogenous pain-inhibitory systems and possibly contribute to a discordance between measures of pain inhibition and pain facilitation. PerspectiveResults of the present study indicated that greater endogenous pain-inhibitory capacity is associated with lower levels of pain facilitation. This association, however, was not significant among opioid users, suggesting that opioids might compromise the functioning and interrelationship between endogenous pain modulatory systems.

Higher Dispositional Optimism Predicts Lower Pain Reduction During Conditioned Pain Modulation

Optimism is associated with lower pain sensitivity, positive adjustment to chronic pain, and greater reduction of pain thresholds in a conditioned pain modulation (CPM) paradigm. We hypothesized that participants with higher levels of optimism would experience greater inhibition of suprathreshold pain during CPM. Seventy-seven healthy adults completed a test of optimism, the Life Orientation Test-Revised, as well as measures of depression, pain catastrophizing, and neuroticism. Participants also underwent psychophysical tests of heat pain tolerance, heat pain threshold, and CPM. CPM magnitude was calculated as the change in heat pain ratings when applied alone and simultaneously with painful pressure. Greater optimism was significantly correlated with reduced CPM magnitude (P = .013). Regression analysis was performed using optimism as a predictor of CPM magnitude while controlling for pain catastrophizing, neuroticism, depression, and age. The overall model was significant (P = .003). Significant positive coefficients were found for depression (P = .014) and optimism (P < .001) scores. These results suggest that greater optimism predicts less inhibition of suprathreshold pain, the opposite of our hypothesis. This unexpected finding may be due to factors such as perceived stress and coping differences, and suggests that modulation of threshold-level and suprathreshold pain involves different underlying mechanisms. PerspectiveThis article reports that greater optimism predicts less inhibition of suprathreshold pain, in contrast with previous work showing that optimism correlates positively with pain threshold reductions. These findings suggest that the association between optimism and the function of endogenous pain modulatory systems is complex and differs for threshold-level and suprathreshold pain.

Opposite Effects of Stress on Pain Modulation Depend on the Magnitude of Individual Stress Response

The effect of acute stress on pain threshold and intolerance threshold are reported as producing either hypoalgesia or hyperalgesia. Yet, the contribution of individual stress reactivity in this respect has not been established. The aim was to test 2 pain modulation paradigms under acute stress manipulation, to our knowledge, for the first time, to study whether stress differentially affects pain modulation, and whether the effect is related to individual stress response. Participants were 31 healthy subjects. Conditioned pain modulation (CPM) and pain adaptation were measured before and after inducing an acute stress response using the Montreal Imaging Stress Task. Subjects' stress response was evaluated according to salivary cortisol, autonomic function, and perceived stress and anxiety. The Montreal Imaging Stress Task induced a validated stress response. On a group level, stress induced reduction in CPM magnitude and increase in pain adaptation compared with baseline. These responses correlated with stress reactivity. When the group was subdivided according to stress reactivity, only high stress responders exhibited reduced CPM whereas only low stress responders exhibited increased pain adaptation. The results suggest that acute stress may induce opposite effects on pain modulation, depending on individual stress reactivity magnitude, with an advantage to low stress responders. PerspectiveThis study evaluated the effect of acute stress on pain modulation. Pain modulation under stress is affected by individual stress responsiveness; decreased CPM occurs in high stress responders whereas increased pain adaptation occurs in low stress responders. Identification of high stress responders may promote better pain management.

Conditioned pain modulation is affected by occlusion cuff conditioning stimulus intensity, but not duration.

Various conditioned pain modulation (CPM) methodologies have been used to investigate diffuse noxious inhibitory control pain mechanisms in healthy and clinical populations. Occlusion cuff parameters have been poorly studied. We aimed to investigate whether occlusion cuff intensity and/or duration influenced CPM magnitudes. We also investigated the role of physical activity levels on CPM magnitude. Two studies were performed to investigate the role of intensity and duration of occlusion cuff conditioning stimulus on test stimulus (tibialis anterior pressure pain thresholds). In Study 1, conditioning stimulus intensity of 2/10 or 5/10 (duration <20s) was evaluated using a paired-samples t-test. In Study 2, duration of 2/10 conditioning stimulus was 3min. One-way repeated-measures ANOVA was used to investigate the effect of time (0, 1, 2 and 3min) on CPM magnitude. In Study 1, 27 healthy volunteers (mean±SD: 24.9years (±4.5); eight female) demonstrated that an occlusion cuff applied to the upper arm eliciting 5/10 local pain resulted in a significant (mean±SD: 17%±46%) increase in CPM magnitude, when compared to 2/10 intensity (-3%±38%, p=0.026), whereas in Study 2, 25 healthy volunteers (22.5years (±2.7); 13 female) demonstrated that 3min of 2/10 CS intensity did not result in a significant change in CPM (p=0.21). There was no significant relationship between physical activity levels and CPM in either study (p>0.22). This study demonstrated that an occlusion cuff of 5/10 conditioning stimulus intensity, when compared to 2/10, significantly increased CPM magnitude. Maintaining 2/10 conditioning stimulus for 3min did not increase CPM magnitude. Dysfunctional conditioned pain modulation (CPM) has been associated with poor health outcomes. Various factors can influence CPM outcomes. The role of occlusion cuff conditioning stimulus intensity and duration has not been previously investigated. Intensity (5/10), but not duration of lower intensity (2/10) conditioning stimulus, affects CPM magnitude.