Conditioned Pain Modulation Effect Research Articles

Changes in Descending Pain Modulation During Anti-Tumor Necrosis Factor Therapy: A Prospective Study in Rheumatoid Arthritis and Spondyloarthritis.

In rheumatoid arthritis (RA) and spondyloarthritis (SpA), managing persistent pain remains challenging. Little is known regarding impaired pain pathways in these patients and the impact of biologic disease-modifying antirheumatic drugs (bDMARDs). The objective of the Rheumatism Pain Inhibitory Descending Pathways study was to assess pain thresholds and descending pain modulation in patients with active RA or SpA following introduction of a tumor necrosis factor inhibitor (TNFi). Patients with active disease (50 with RA and 50 with SpA) naive to bDMARDs or targeted synthetic DMARDs and starting a TNFi were included. Patients were observed for six months after TNFi initiation with clinical, psychological, and pain assessment. At all visits, participants underwent quantitative sensory testing with heat and cold pain thresholds and descending inhibition by conditioned pain modulation (CPM). Descending pain control (CPM effect) was assessed as the change in heat pain threshold (°C) following a conditioning stimulus. Of the 100 patients (59 women, mean ± SD age 45.8 ± 14.6 years), 74 completed the six-month follow-up. Thermal pain thresholds did not significantly change during follow-up. CPM effect improved significantly during follow-up (mean ± SD 0.25 ±2.57°C at baseline and 2.96 ± 2.50°C at six months; P < 0.001). At the end of follow-up, the mean CPM effect was significantly higher in patients without significant pain compared with patients with persistent pain (>3 of 10 on the Brief Pain Inventory) (mean ± SD 3.25 ± 2.68°C vs 2.47 ± 2.11°C; P = 0.04) and in patients achieving remission or low disease activity compared with patients with active rheumatism (mean ± SD 3.31 ± 2.68°C vs 2.18 ± 1.87°C; P = 0.01). In active inflammatory rheumatisms, impaired descending pain modulation, but not thermal pain thresholds, is improved after TNFi treatment, suggesting a possible effect of TNFi on central pain modulation.

Individual differences in conditioned pain modulation are associated with functional connectivity within the descending antinociceptive pathway.

The perception of pain and ability to cope with it varies widely amongst people, which in part could be due to the presence of inhibitory (antinociceptive) or facilitatory (pronociceptive) effects in conditioned pain modulation (CPM). This study examined whether individual differences in CPM reflect functional connectivity (FC) strengths within nodes of the descending antinociceptive pathway (DAP). A heat-based CPM paradigm and resting-state functional magnetic resonance imaging (rs-fMRI) were used to test the hypothesis that an individual's capacity to exhibit inhibitory CPM (changes in test stimuli [TS] pain due to a conditioning stimulus [CS]) reflects FC of the subgenual anterior cingulate cortex (sgACC), periaqueductal gray (PAG), and rostral ventromedial medulla (RVM). A total of 151 healthy participants (72 men, 79 women) underwent CPM testing and rs-fMRI. Three types of CPM were identified based on the effect of the CS on TS pain: (1) Antinociception: CS reduced TS pain in 45% of participants, (2) No-CPM: CS did not change TS pain in 15% of participants, and (3) Pronociception: CS increased TS pain in 40% of participants. Only the Antinociceptive subgroup exhibited FC between the left sgACC and PAG, right sgACC and PAG, and RVM and PAG. Furthermore, only the Antinociceptive subgroup exhibited a correlation of both left and right sgACC-RVM FC (medium effect sizes) with CPM effect magnitude. Women, compared with men were more likely to be categorized as pronociceptive. These data support the proposition that FC of the DAP reflects or contributes to inhibitory CPM.

Conditioned Pain Modulation Differences in Central and Peripheral Burning Mouth Syndrome (BMS) Patients.

To evaluate conditioned pain modulation (CPM) in burning mouth syndrome (BMS) patients with different pain mechanisms. Twenty BMS patients (52.0 ± 6.8 years, 17 women and 3 men) and age- and gender-matched 22 healthy controls were enrolled in this randomised controlled trial. The patients received an active lingual nerve block (lidocaine) and a placebo injection (saline) randomly with an interval of 1 week in a double-blinded manner. Patients evaluated their pain intensity on a 0- to 10-cm visual analogue scale (VAS) before and after each injection, with or without CPM. Based on the anaesthesia effect, BMS patients were divided into two groups with presumed different pain mechanisms; a 'central subgroup (n = 11)' with pain relief less than 1 cm and 'peripheral subgroup (n = 9)' with pain relief more than 1 cm on the VAS. Mechanical pain threshold (MPT) and wind-up ratio (WUR) were investigated at two oral mucosa regions: the region with most intense symptoms and a control region for the patient group; tongue and buccal region for the control group. CPM was induced by immersing the left hand into cold water. A moderate level of pain (around five on the VAS) was obtained by adjusting the water temperature. MPT and WUR were measured twice for all the participants with and without CPM, which was analysed and presented as relative change in MPT and WUR. Differences between groups were analysed using two-way ANOVA. Differences within group between tests were assessed by paired t-test. At baseline, there were no significant group differences for MPT or WUR between BMS patients and healthy controls (p ≥ 0.156). The mean bath temperature to evoke moderate pain for the BMS group was significantly lower than that for the healthy control group (8.9°C vs. 11.9°C, p = 0.003). The CPM evoked an inhibitory modulation in 18.2%-44.4% of BMS patients, while for the healthy group, the ratio was 68.2%-81.8%. Central BMS patients had smaller CPM effects than healthy participants at the painful site and control site, which indicated a decreased CPM function (p ≤ 0.034). Peripheral BMS patients had lower CPM effects than healthy participants only at the painful site (p = 0.037). The present findings documented impairment of central nociceptive inhibition processing in BMS patients which was more extensive in central BMS than peripheral BMS. These findings add to the suggestion that BMS may a heterogeneous pain condition with at least two different phenotypes.

Altered Sensory Processing in People Attending Specialist Orthopaedic Consultation for Management of Persistent Shoulder Pain: An Observational Cross-Sectional Study.

OBJECTIVES: The primary objective was to compare sensory processing measures in people attending specialist orthopaedic consultation for management of persistent shoulder pain with control participants. The secondary objective was to compare the groups' sociodemographic, clinical, general health and lifestyle, and psychological characteristics. DESIGN: Observational cross-sectional. METHODS: Participants with shoulder pain for ≥3 months, who attended a public hospital orthopaedic department (n = 119), and community participants without shoulder pain (n = 44) underwent a standardized quantitative sensory testing protocol, measuring pressure pain threshold, temporal summation, and conditioned pain modulation. Sociodemographic, clinical, general health and lifestyle, and psychological characteristics were also collected. RESULTS: Participants with shoulder pain had significantly lower pressure pain thresholds at all sites (ie, local and widespread mechanical hyperalgesia) and significantly decreased conditioned pain modulation effect (ie, descending inhibition of nociception) than control participants. There was no significant difference between groups for temporal summation. Participants with shoulder pain had decreased general health and function, less healthy lifestyles, and poorer psychological health compared with controls. CONCLUSION: People referred to specialist orthopaedic care for management of persistent shoulder pain had clinical signs of altered sensory processing and poor health outcomes. J Orthop Sports Phys Ther 2024;54(10):1-10. Epub 25 July 2024. doi:10.2519/jospt.2024.12512.

Understanding inter-individual variability of experimental pain habituation and conditioned pain modulation in healthy individuals

Although reduced experimental pain habituation is proposed as a proxy of diminished endogenous pain modulatory capacity in chronic pain, prior studies show contradictory findings. Even across healthy participants, pain habituation varies substantially, which may relate to another measure of endogenous pain modulation, i.e., conditioned pain modulation (CPM). Hence, this study investigated the relationship between pain habituation and CPM. Pain habituation was assessed in 45 healthy participants between two blocks of 15–20 contact-heat stimuli applied to the hand. Habituation of subjective pain ratings and objective neurophysiological readouts (contact-heat evoked potential (CHEP) and palmar sympathetic skin response (SSR)) was investigated. CPM was assessed by comparing heat pain thresholds before and after hand immersion in a noxious cold (9 °C) and lukewarm water bath (32 °C, to control for repeated measures effects). Pain habituation showed a large variability, with subjective but not objective pain habituation correlating with cold-induced CPM effects (r = 0.50; p = 0.025). This correlation was not observed for ‘true’ CPM effects (corrected for repeated measures effects) nor for CPM effects induced by a lukewarm water bath. These findings suggest that the observed variability in subjective pain habituation may be influenced by both descending endogenous pain modulation and peripheral adaptation processes associated with repeated measures. Objective pain habituation readouts, i.e., CHEPs and SSRs, capture different, complementary aspects of endogenous pain modulation.

Somatosensory profile in individuals with duchenne muscular dystrophy: A quantitative sensory testing (QST) study

ObjectiveThis study aimed to quantify somatosensory profiles in individuals with Duchenne muscular dystrophy (DMD). MethodsWe included 28 participants with genetically confirmed DMD (aged 8–17 years), 14 with chronic pain (DMD-CP), and 14 without pain (DMD-NP), compared to 13 healthy controls (HC) matched for age and sex. Three quantitative sensory testing (QST) modalities were examined: pressure pain threshold (PPT), temporal summation of pain (TSP) and conditioned pain modulation (CPM). Characteristics related to chronic pain, fatigue, psychological distress, and health-related quality of life were assessed using questionnaires. ResultsDecreased PPTs were found in both DMD cohorts across body areas commonly affected by pain (rectus femoris, medial gastrocnemius, paraspinal muscles, upper trapezius), as well as in a less frequently affected remote area (thenar eminence), compared to HCs (p < 0.001). The DMD-CP group exhibited greater TSP compared to HCs (p = 0.025). There were no differences in CPM effects between DMD groups and HCs. No differences were detected in all QST measures between DMD-CP and DMD-NP. SignificanceThis study is the first to explore the somatosensory profile in DMD. Preliminary evidence suggests that generalized hyperalgesia may be a common feature in DMD regardless of pain status. QST measures appear to not distinguish individuals with chronic pain from those without and thus are not recommended for assessing pain in DMD or guiding treatment.

Is predictability of the conditioning stimulus (CS) a critical factor in conditioned pain modulation (CPM)?

Introduction Conditioned pain modulation (CPM) allows to investigate endogenous pain modulation and its clinical outcomes. Although co-activation of emotions has been shown to affect CPM, the impact of ‘threat,’ which may accompany CPM stimulation itself, has been mostly neglected. A critical factor for the threat level of the conditioning stimulus (CS) may be its predictability. Methods 38 healthy participants (18 female) took part in a CPM study with pressure stimulation on the leg (blood-pressure cuff) serving as CS and heat stimulation on the forearm (contact thermode; CHEPS) serving as test stimulus (TS). While CS varied in intensity and –as operationalisation of threat– in temporary predictability, TS was kept constant. CPM effects were studied by EEG parameters (N2P2) and pain ratings. Results We found a significant CPM effect when considering N2P2, with low CS predictability augmenting CPM inhibition; in contrast, a surprisingly facilitatory CPM effect occurred in pain ratings (in the high CS predictability condition). The threat manipulation was only partially successful because CS intensity increased the threat ratings but not -as intended- CS predictability. Correlations between subjective and psychophysiological CPM responses were low. Discussion The differing CPM effects in subjective and psychophysiological responses, with both inhibitory and facilitatory effects, is puzzling but has already been observed earlier. The consideration of the CPM stimulation as major threat that is emotionally active is theoretically clearly justifiable but the operationalisation by means of different levels of CS predictability as in the present study might not have been ideal. Thus, further attempts of experimental verification are warranted.

Effect of Transcutaneous Auricular Vagus Nerve Stimulation on Conditioned Pain Modulation in Trigeminal Neuralgia Patients.

Conditioned pain modulation (CPM) is a quantitative estimation of the capacity for endogenous pain modulation. Reduced CPM enables chronic painful event development or exacerbates pre-existing pain symptoms. Emerging reports indicate that patients with trigeminal neuralgia (TN) have dysregulated endogenous pain modulation. Transauricular vagus nerve stimulation (taVNS) is known to alleviate both acute and chronic pain symptoms. Its role in modulation or management of TN remains unknown. Here, we evaluated the taVNS efficacy in modulating CPM among TN patients. Conclusions from this investigation may facilitate establishment of novel non-invasive adjunctive approaches to treating TN patients. All research work was conducted at the First Affiliated Hospital of the University of Science and Technology of China (Anhui Provincial Hospital). In all, we recruited 62 study participants, 31 TN patients and 31 healthy volunteers, for a 2-day experimental test. At the beginning of the experiment (Day 1), all subjects received 30min of active taVNS. On Day 2, they received sham taVNS with the same duration and intensity. Meanwhile, technicians documented participant pressure pain thresholds (PPT) and CPM values at baseline, and at 15 and 30min post-active or sham taVNS. A 30-min active taVNS exposure substantially elevated the PPT and CPM effect (P<0.05) among TN patients, and we also observed a notable rise in the PPT and CPM effect (P<0.05) among healthy controls. Additionally, there were no serious adverse events from the administered treatment. Exposure to 30min of active taVNS strongly augmented the CPM effect and elevated the PPT among TN patients and healthy controls. These effects were not observed with sham stimulation. Despite the limitations inherent to survey studies, such as duration and compliance biases, we consider that taVNS is a promising, safe, and cost-effective therapy. In future investigations, we recommend assessment of long-term taVNS application and its effects on CPM and clinical pain. ChiCTR2300078673 ( www.Chictr.org.cn ).

Comparable Conditioned Pain Modulation and Painful-Exercise-Induced Hypoalgesia in Healthy Young Adults: A Randomized Crossover Trial

Conditioned pain modulation and exercise-induced hypoalgesia reflect inhibitory pain controls emanating from the brain. The aim of this study was to compare the extent of pain inhibition from exercise-induced hypoalgesia (isometric wall squat), conditioned pain modulation (cold-water immersion), and their combination (wall squat followed by cold water in fixed order) in healthy pain-free adults. Sixty-one participants (median age 21 years) completed 3 sessions (wall-squat, cold-water, and combined) in random order. Sessions were separated by at least a week. In each session, pressure-pain thresholds, single-pinprick-pain ratings, and pinprick-temporal summation of pain (the fifth minus the first) were obtained at quadriceps, forearms, and forehead, before and after wall squat and/or cold water. Each intervention inhibited pain to pressure (partial η2 = .26) and single pinprick (partial η2 = .16) to a similar extent; however, pressure-pain inhibition was negligible in the forehead. After adjusting for age and sex, single-pinprick-pain inhibition in the forehead induced by wall squat was associated with that induced by cold water (adjusted R2 = .15; P = .007), and stronger pain inhibition was predicted by a higher thigh-pain rating to wall squat (adjusted R2 = .10; P = .027). Neither intervention affected pinprick-temporal summation of pain. Together, the findings suggest that pain-inhibitory effects of exercise-induced hypoalgesia and conditioned pain modulation may overlap when exercise is at least moderately painful (6/10 intensity). Pressure pain in body regions remote from the exercised or conditioned sites may be weakly modulated. PerspectiveThe current findings suggest that pain-inhibitory effects induced by painful wall squat and by cold-water immersion may overlap. The magnitude of pain inhibition in the forehead remote from the exercised thigh or the conditioned foot appears smaller, which could be examined further in future research.

Pupillometry as a Potential Objective Measurement of Pain Assessment in Healthy Volunteers.

Pain leads to activation of the autonomic nervous system and thus, among other things, to pupillary reflex dilation (PRD). Previous studies have already confirmed a correlation between the perception of pain and the pupillary reaction, measured using pupillometry. However, the previous study populations were under the influence of medication for analgesia in perioperative setting or suffered from pain. This study examines the relationship between pupillary reaction and pain perception in healthy controls and addresses the question of whether endogenous pain inhibition, clinically tested by conditioned pain modulation (CPM), can be quantified using pupillometry. Forty-two healthy volunteers (21 females, 21 males, mean age 27.9 ± 5.8 years, range 20-39 years) were included in this study. The PRD, as a measure of the pupillary reaction (variance from the base diameter in percent), was investigated during baseline, heat application and during CPM testing and results compared to the reported pain intensity on the numerical rating scale (NRS). The volunteers showed higher variances under painful conditions compared to the measurement at rest corresponding to higher sympathetic activity during pain. Volunteers with a higher variance, ie a stronger pupillary reaction, gave higher pain ratings than subjects with a lower pupil variance. However, there was no correlation between the NRS and PRD. PRD and pain ratings during CPM were significantly lower compared to heat pain application alone. However, there was no correlation between the calculated CPM effect and the PRD. Pupillometry is capable of objectively reflecting the pain response, eg pain relief through CPM testing. However, the CPM effect calculated from the subjective pain ratings and the objective PRD measurements is not associated suggesting that both measure different aspects of pain perception. It must be discussed whether the CPM effect can be the correct measure for the functionality of the pain system.

Exploring the Impact of Affinity and Unpleasantness on Conditioned Pain Modulation among Healthy Individuals.

The variability of the Conditioned Pain Modulation (CPM) effect can be attributed to conditioning stimulus (CS) characteristics, such as intensity, duration, unpleasantness, or affinity. This study investigates the impact of affinity and unpleasantness variables on the CPM effect using two protocols (cold water and ischemia) in the same healthy individuals (n = 54). Additional variables were also examined for their potential influence on the CPM effect. The main results are as follows: (1) a higher level of affinity and a lower level of unpleasantness for the stimuli used resulted in a stronger CPM effect; (2) significant differences were observed in the extreme categories (high and low) of both variables, whereas the 'indifferent' group did not show a clear trend; (3) within-subject analysis demonstrated that affinity for the CS had a clear impact on the CPM effect; (4) no correlations were found between the CPM effect and the additional variables, except for the extraversion variable with the CPM effect of the ischemia protocol, and CS duration variable with CPM effect in the cold water protocol; and (5) only the affinity variable explained the CPM effect in both protocols in the multiple linear regression analysis. The affinity variable was found to influence the CPM effects significantly, indicating its important role in our perception and response to pain.

Correlations of The Central Sensitization Inventory, conditioned pain modulation, cognitions and psychological factors in individuals with chronic neck pain: A cross-sectional study.

Chronic neck pain (CNP) is a global public health problem, with high prevalence and absenteeism rates. Central sensitization (CS) as a basis for chronic pain may play an essential role in its development and progression. It is often comorbid with low conditioned pain modulation (CPM) effects, cognitions, and psychological problems. The purposes of this study were to (1) explore the relationship between pain-related cognitions and psychological factors, CPM effects, and the central sensitization inventory (CSI) scores; and (2) determine whether cognitions and psychological factors can predict CSI scores and CPM effects in individuals with CNP. Fifty-four individuals with CNP were recruited for this cross-sectional study. The following outcome measures were evaluated: The CSI (screening tool) was compared with the cold pressor test (CPT), which was the psychophysical test used to assess the CPM; neck pain intensity using the visual analogue scale (VAS), as well as pain-related cognitions (including kinesiophobia and pain catastrophization) and psychological states (including anxiety and depression) using self-report questionnaires. CSI score was not associated with the CPM effect (r = 0.257, p > 0.05), and no cognitions or psychological factors were associated with CPM (p > 0.05), but CSI score was moderately positively correlated with kinesiophobia (r = 0.554, p < 0.01), lowly positively correlated with pain catastrophization (r = 0.332, p = 0.017) and anxiety (r = 0.492, p < 0.01), but not depression (r = 0.207, p = 0.132). Multiple linear regression analysis showed that kinesiophobia (B = 1.308, p < 0.01) and anxiety (B = 1.806, p = 0.02) were significant positive predictors of CSI score. The findings confirm some of our hypotheses. Accordingly, the findings inferred that the CSI does not seem to respond to CPM effect in patients with CNP effectively. In addition, CSI score was associated with cognitions and psychological factors, of which kinesiophobia and anxiety were effective predictors. In clinical practice, pain-related cognitions and psychological factors should be fully considered to manage neck pain efficiently.

Sex differences in conditioned pain modulation effects and its associations with autonomic nervous system activities in healthy, younger individuals: a pilot study.

Sex differences in conditioned pain modulation (CPM) have not been sufficiently explored. This pilot study aimed to examine sex differences in CPM effects and associations between autonomic activities and CPM effects in healthy, younger individuals. University students were recruited from February to March 2021 and divided by sex. They remained seated for 10 minutes as a rest period, then immersed their right hands in cold water for 2 minutes as a cold period. The pressure pain threshold (PPT) was measured after each period, presenting the CPM index (%) using the formula: (PPTcold/PPTrest) × 100. Autonomic nervous system variables were calculated using the formula-(autonomic variablecold/autonomic variablerest) × 100-and suffixed by "index" such as low-frequency/high-frequency (LF/HF) index. Some psychological questionnaires were self-recorded. Sex differences in the CPM index were statistically compared, and a simple linear regression analysis between the CPM and autonomic indices was conducted. Thirty-two participants were analyzed (14 women and 18 men; aged 21.1 ± 0.6 and 20.9 ± 0.3 years, respectively). Conditioned pain modulation effects were not different at 127.0 ± 19.1% in women and 124.0 ± 18.7% in men. The LF/HF index, LF normalized unit (nu) index (LFnu), and HFnu index had significant predictor variables for the CPM index across overall samples. The LF/HF index and LFnu index were significant predictor variables for the CPM index for women but not for men. Conditioned pain modulation effects between groups seem to be similar. The LF/HF and LFnu indices in women were significant, indicating that descending pain modulations in women might be more associated with autonomic activities than those in men.

Botulinum toxin-A effects on pain, somatosensory and psychosocial features of patients with refractory masticatory myofascial pain: a randomized double-blind clinical trial

The antinociceptive effect of BoNT-A have been well documented in animal studies; however, results of few but well-designed randomized placebo-controlled clinical trials about BoNT-A efficacy in masticatory myofascial pain (MFP) are inconsistent. Therefore, the present randomized, double-blind, placebo-controlled clinical trial evaluated the efficacy of BoNT-A in patients with refractory MFP. Twenty-eight patients with pain reduction of less than 30% despite conservative treatment and with an average pain intensity of > 50 mm on the visual analogue scale (VAS) participated. Patients were randomly assigned to receive a total of 80 U of BoNT-A or saline solution (SS) injected into the masseter and anterior temporalis muscles. Pain intensity (VAS), quantitative sensory testing (QST), conditioned pain modulation (CPM), and psychosocial status were examined. Follow-up was performed at 1 and 6 months. For repeated-measure comparisons between evaluation times, Friedman test with Bonferroni correction was used for pain and somatosensory variables and the Wilcoxon test for the psychosocial variables. The Mann–Whitney test was used for all comparisons between groups. The BoNT-A group had a significant decrease in pain intensity at follow-ups compared with the SS group (p < 0.001). QST assessment revealed higher pressure pain threshold values in the masseter muscle for BoNT-A group compared to SS (p < 0.03) at all follow-ups. No differences were found for mechanical pain threshold and wind-up ratio values (p > 0.05) in the entire study. The BoNT-A group presented the most efficient CPM effect (p < 0.03) only at the 1 month follow-up in the masseter muscle. There was a significant time effect for BoNT-A in all psychosocial variables (p < 0.05) and a drug effect in the Central Sensitization Inventory (p < 0.01), Pittsburgh Sleep Quality Index (p < 0.004), and Healthy Survey 36 (p < 0.05) at 6 months follow-up. The study demonstrates that a single injection-session of BoNT-A has positive effects on the hall pain spectrum of patients with refractory masticatory myofascial pain.

Association between myofascial trigger point therapy and conditioned pain modulation

IntroductionMyofascial trigger point therapy (MTrP) is a widely used therapeutic approach, although the underlying mechanisms remain unclear. Mechanisms discussed include peripheral involvement of muscles as well as central pain modulating processes such as the conditioned pain modulation (CPM). The aim of this study was to investigate whether the analgesic response of MTrP and the analgesic response of CPM correlate in asymptomatic participants in order to identify shared underlying mechanisms of MTrP and CPM. MethodBoth, CPM and MTrP protocols consisted of heat-based test stimuli (heat pain thresholds before and after the intervention) and pressure-based (conditioning) stimuli. Asymptomatic participants (n = 94) were randomly assigned to receive either mild, intense or no pressure stimuli (between-group design) to both the fingernail and the MTrP of the infraspinatus muscle (within-group design). Pressure stimuli at both locations (fingernail, MTrP) were applied with a pressure algometer for 120 s and continuously adjusted to maintain a constant pain intensity of mild or intense pain. All thermal stimuli were applied on the lower leg with a thermal stimulator. ResultsA significant correlation was shown between the analgesic effect of CPM and MTrP therapy for mild (r = 0.53, p = 0.002) and intensive stimuli (r = 0.73, p < 0.001). 17.3% of the variance of the MTrP effect were explained by CPM after mild stimulation, and 47.1% after intense stimulation. Pain-related characteristics did not explain the variance within the analgesic response using a regression analysis. ConclusionsBetween the analgesic responses following MTrP and CPM paradigms, a moderate to strong correlation was observed, suggesting shared underlying mechanisms.

Neurophysiological oscillatory markers of hypoalgesia in conditioned pain modulation.

Conditioned pain modulation (CPM) is an experimental procedure that consists of an ongoing noxious stimulus attenuating the pain perception caused by another noxious stimulus. A combination of the CPM paradigm with concurrent electrophysiological recordings can establish whether an association exists between experimentally modified pain perception and modulations of neural oscillations. We aimed to characterize how CPM modifies pain perception and underlying neural oscillations. We also interrogated whether these perceptual and/or neurophysiological effects are distinct in patients affected by chronic pain. We presented noxious electrical stimuli to the right ankle before, during, and after CPM induced by an ice pack placed on the left forearm. Seventeen patients with chronic pain and 17 control participants rated the electrical pain in each experimental condition. We used magnetoencephalography to examine the anatomy-specific effects of CPM on the neural oscillatory responses to the electrical pain. Regardless of the participant groups, CPM induced a reduction in subjective pain ratings and neural responses (beta-band [15-35 Hz] oscillations in the sensorimotor cortex) to electrical pain. Our findings of pain-induced beta-band activity may be associated with top-down modulations of pain, as reported in other perceptual modalities. Therefore, the reduced beta-band responses during CPM may indicate changes in top-down pain modulations.

Effect of Catastrophic Thinking on the Analgesic Effect of Electroacupuncture.

Patients with chronic pain and high-level catastrophic thoughts often do not respond to acupuncture. This may be related to hypofunctioning of the dorsolateral prefrontal cortex and the descending pain inhibitory system. Therefore, we examined the relationship between the level of catastrophic thinking and the analgesic effect of electroacupuncture using the pain catastrophizing scale (PCS). We also evaluated the descending pain inhibitory system using conditioned pain modulation (CPM) and offset analgesia (OA). The relationship between catastrophic thinking and the descending pain inhibitory system was also examined. After testing the hospital anxiety and depression scale and the PCS in 14 healthy adults, the current pain threshold (CPT), CPM, and OA were measured, in order, before the intervention. Thereafter, electroacupuncture was applied to 3 limbs (the dominant hand and both lower extremities) at 4 Hz, and to the scalp at 100 Hz, for 30 minutes, and the CPT was measured again immediately after the intervention. The difference in the CPT before and after the intervention was taken as the analgesic effect. The participants were divided into 2 groups, the H-PCS group (≥16 points) and the L-PCS group (≤15 points), according to the PCS score, and the analgesic effects of electroacupuncture were significantly different (P = 0.04). However, no relationship was found between the PCS score and the CPM (r = -0.02, P = 0.94) and OA effects (r = -0.19, P = 0.49). It was suggested that people with high-level catastrophic thinking may find it difficult to obtain the analgesic effects of electroacupuncture.

Effects of virtual reality on psychophysical measures of pain: superiority to imagination and nonimmersive conditions.

Virtual reality (VR) has been shown to be effective in pain management. However, to date, little is known about the mechanisms by which immersive experiences influence pain processing. The aim of this study was to investigate the direct effects of an immersive VR environment on the perception of experimental pain in individuals with chronic pain and pain-free controls. The immersion in a VR landscape was compared with mental imagery and a nonimmersive control condition. Using a randomized within-crossover design, pressure pain detection and tolerance thresholds, spatial and temporal summation (SSP, TSP), and conditioned pain modulation (CPM) were measured in 28 individuals with chronic pain and 31 pain-free controls using phasic cuff pressure on the legs. Direct comparison between the groups showed that although individuals with pain had significantly lower pain thresholds, reduced CPM effects, and increased TSP, the VR condition had the same pain-inhibitory effect on pain thresholds as in pain-free controls. Conditioned pain modulation effects were reduced by all conditions compared with baseline. There were no significant differences between conditions and baseline for TSP and SSP. Overall, pain modulatory effects were largest for VR and smallest for imagery. These results demonstrate that immersion in a VR environment has an increasing effect on pain thresholds, reduces pain inhibition in a CPM paradigm, and has no effects on TSP. This applies for participants with chronic pain and pain-free controls. These VR effects exceeded the effects of mental imagery on the nonimmersive control condition. This indicates that VR effectively modulates pain perception in both patients and controls irrespective of differences in pain perception.

Is conditioned pain modulation (CPM) affected by negative emotional state?

Conditioned pain modulation (CPM) is an experimental paradigm, which describes the inhibition of responses to a noxious or strong-innocuous stimulus, the test stimulus (TS), by the additional application of a second noxious or strong-innocuous stimulus, the conditioning stimulus (CS). As inadequate CPM efficiency has been assumed to be predisposing for clinical pain, the search for moderating factors explaining inter-individual variations in CPM is ongoing. Psychological factors have received credits in this context. However, research concerning associations between CPM and trait factors relating to negative emotions has yielded disappointing results. Yet, the influence of anxious or fearful states on CPM has not attracted much interest despite ample evidence that negative affective states enhance pain. Our study aimed at investigating the effect of fear induction by symbolic threat on CPM. Thirty-seven healthy participants completed two experimental blocks: one presenting aversive pictures showing burn wounds (high-threat block) and one presenting neutral pictures (low-threat block). Both blocks contained a CPM paradigm with contact heat as TS and hot water as CS; subjective numerical ratings as well as contact-heat evoked potentials (CHEPs) were assessed. We detected an overall inhibitory CPM effect for CHEPs amplitudes but not for pain ratings. However, we found no evidence for a modulation of CPM by threat despite threat ratings indicating that our manipulation was successful. These results suggest that heat/thermal CPM is resistant to this specific type of symbolic threat induction and further research is necessary to examine whether it is resistant to fearful states in general. The attempt of modulating heat conditioned pain modulation (CPM) by emotional threat (fear/anxiety state) failed. Thus, heat CPM inhibition again appeared resistant to emotional influences. Pain-related brain potentials proved to be more sensitive for CPM effects than subjective ratings.

Pain history and experimental pressure pain responses in adolescents: Results from a population-based birth cohort.

Sensitized pain mechanisms are often reported in musculoskeletal pain conditions, but population-based paediatric studies are lacking. We assessed whether adolescents with musculoskeletal pain history had evidence of increased responsiveness to experimental pressure stimuli. Data were from 1496 adolescents of the Generation XXI birth cohort. Pain history was collected using the Luebeck Pain Questionnaire (self-reported at 13, parent-reported at 7 and 10 years). Two case definitions for musculoskeletal pain were considered: (1) cross-sectional-musculoskeletal pain lasting more than 3 months at age 13 and (2) longitudinal-musculoskeletal pain at age 13 with musculoskeletal pain reports at ages 7 and/or 10. Lower limb cuff pressure algometry was used to assess pain detection and tolerance thresholds, conditioned pain modulation effects (CPM, changes in thresholds in the presence on painful conditioning) and temporal summation of pain effects (TSP, changes in pain intensity to 10 phasic painful cuff stimulations). Adolescents with musculoskeletal pain at age 13 plus a history of pain in previous evaluations (longitudinal definition) had lower pain tolerance thresholds compared to the remaining sample (40.2 v. 49.0 kPa, p = 0.02), but showed no differences in pain detection threshold, CPM effect and TSP effect. Pain sensitivity, CPM effects and TSP effects were not significantly different when the current pain only case definition (cross-sectional) was used. Adolescents with current musculoskeletal pain who had a history of pain since childhood had lower tolerance to cuff stimulation. This may suggest long-standing musculoskeletal pain since childhood may contribute to sensitisation, rather than the presence of current pain only. Repeated musculoskeletal pain up to age 13 years may contribute to higher pain sensitivity (particularly lowered pressure pain tolerance) in the general adolescent population. This does not seem to be the case when reported pain experiences are recent or when the outcomes are temporal pain summation or CPM. In this community-based paediatric sample, the vast majority showed no sign of altered pain processing, but a small fraction may reveal some pain sensitization at 13 years of age.