Conditioned Pain Modulation Effect Research Articles

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.

Conditioned pain modulation does not differ between people with lower-limb tendinopathy and non-tendinopathy controls: a systematic review with individual participant data meta-analysis.

OBJECTIVE: To explore whether people with lower-limb tendinopathy have reduced relative conditioned pain modulation (CPM) when compared to non-tendinopathy controls. DESIGN: Systematic review with individual participant data (IPD) meta-analysis. LITERATURE SEARCH: Eight databases were searched until 29 August 2022. STUDY SELECTION CRITERIA: Cross-sectional studies comparing the magnitude of the CPM effect in people with lower-limb tendinopathy to non-tendinopathy controls in a case-control design. DATA SYNTHESIS: Included studies provided IPD, which was reported using descriptive statistics. Generalised estimating equations (GEE) determined between-group differences in the relative CPM effect, when adjusting for co-variables. Study quality was assessed using a Joanna Briggs Institute checklist and certainty of the evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations. RESULTS: Five records were included, IPD were provided for four studies (n=219 with tendinopathy, n=226 controls). The principal GEE (model one) found no significant relative CPM effects for tendinopathy versus controls (B=-1.73, p=0.481). Sex (B=4.11, p=0.160), age (B=-0.20, p=0.109) and body mass index (B=0.28, p=0.442) did not influence relative CPM effect. The Achilles region had a reduced CPM effect (B=-22.01, p=0.009). In model two (adjusting for temperature), temperature (B=-2.86, p=0.035) and female sex (B=21.01, p=0.047) were associated with the size of the relative CPM effect. All studies were low-quality, and the certainty of the evidence was moderate. CONCLUSION: There were no between-group differences in the magnitude of the CPM effect, suggesting clinicians should manage lower-limb tendinopathy using interventions appropriate for peripherally-dominant pain (e.g., tendon loading exercises such as heavy slow resistance). Based on the 'moderate' certainty evidence, future studies are unlikely to substantially change these findings.

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.

Effects of conditioned pain modulation on Capsaicin-induced spreading muscle hyperalgesia in humans.

Muscle pain can be associated with hyperalgesia that may spread outside the area of primary injury due to both peripheral and central sensitization. However, the influence of endogenous pain inhibition is yet unknown. This study investigated how endogenous pain inhibition might influence spreading hyperalgesia in experimental muscle pain. Conditioned pain modulation (CPM) was assessed in 30 male volunteers by cold pressor test at the non-dominant hand as conditioning and pressure pain thresholds (PPT) at the dominant 2nd toe as test stimuli. Subjects were classified as having inhibitory or facilitating CPM based on published reference values. Subsequently, muscle pain and hyperalgesia were induced by capsaicin injection into the non-dominant supraspinatus muscle. Before and 5, 10, 15, 20, 30, 40, 50 and 60 min later, PPTs were recorded at the supraspinatus, infraspinatus and deltoid muscle, ring finger and toe. Compared to baseline, PPTs decreased at the supraspinatus, infraspinatus and deltoid muscle (p≤0.03), and increased at the finger and toe (p<0.001). In facilitating CPM (n=10), hyperalgesia occurred at 5, 10, 15, 20 and 40 min (p≤0.026). In inhibitory CPM (n=20), hyperalgesia only occurred after 10 and 15 min (p≤0.03). At the infraspinatus muscle, groups differed after 5 and 40 min (p≤0.008). The results suggest that facilitating CPM is associated with more spreading hyperalgesia than inhibitory CPM. This implies that poor endogenous pain modulation may predispose to muscle pain and spreading hyperalgesia after injury, and suggest that strategies to enhance endogenous pain modulation may provide clinical benefits.

Pain-related cognitions and emotional distress are not associated with conditioned pain modulation: an explorative analysis of 1142 participants with acute, subacute, and chronic pain.

Reduced conditioned pain modulation (CPM) and psychological distress co-occur frequently in many pain conditions. This study explored whether common negative pain cognitions and emotional factors were related to lower CPM in individuals across the spectrum from acute to chronic pain. Previously collected data on the CPM effect, pain-related cognitions (fear of movement, pain catastrophizing), and emotional distress (depression, anxiety) through questionnaires from 1142 individuals with acute, subacute, or chronic pain were used. The presence of negative psychological factors was dichotomized according to cutoff values for questionnaires. Associations between the presence of each negative psychological factor and the amplitude of pain reduction in the CPM paradigm was explored with Generalized Linear Models adjusted for sex, age, body mass index, and pain duration. A secondary analysis explored the cumulative effect of psychological factors on CPM. When dichotomized according to cutoff scores, 20% of participants were classified with anxiety, 19% with depression, 36% with pain catastrophizing, and 48% with fear of movement. The presence of any negative psychological factor or the cumulative sum of negative psychological factors was associated with lower CPM (individual factor: β between -0.15 and 0.11, P ≥ 0.08; total: β between -0.27 and -0.12, P ≥ 0.06). Despite the common observation of psychological factors and reduced CPM in musculoskeletal pain, these data challenge the assumption of a linear relationship between these variables across individuals with acute, subacute, and chronic pain. Arguably, there was a nonsignificant tendency for associations in nonexpected directions, which should be studied in a more homogenous population.

Immediate effects of dry needling on pain sensitivity and pain modulation in patients with chronic idiopathic neck pain: a single-blinded randomized clinical trial

BackgroundDry needling is frequently used for the treatment of neck pain but knowledge about its neurophysiological central effects is scarce. ObjectivesTo compare the immediate effects of a single session of dry needling (DN) and sham needling (SN) on local and distant pressure pain thresholds and conditioned pain modulation in patients with chronic idiopathic neck pain. MethodParticipants with chronic idiopathic neck pain were randomly allocated to a DN or SN group. The primary outcome measure was the pressure pain threshold (PPT) at one peripheral location: quadriceps muscle (Q). Secondary outcome measures were local PPTs at the treated (most painful) (tUT) and non-treated upper trapezius muscle (ntUT), absolute and relative conditioned pain modulation (CPM) effects and pain during hot water immersion. Patients were assessed at baseline and immediately post intervention. Linear mixed models were used to examine interaction effects as well as between- and within-group differences. ResultsFifty-four participants were included for statistical analysis. Linear mixed model analyses showed no significant “group X time” interaction effects for any of the outcome measures. The relative CPM effect at the Q was significantly higher post-intervention, compared to baseline within the DN group (mean difference= 13.52%; 95% CI: 0.46, 26.59). ConclusionThe present study shows no superior effect of DN, compared to SN, in the immediate effect on local and distant PPTs and CPM in patients with chronic idiopathic neck pain.

Photobiomodulation enhanced endogenous pain modulation in healthy volunteers

To examine the effects of photobiomodulation (PBM) in healthy volunteers using photonic stimulation of acupuncture points on conditioned pain modulation (CPM), temporal summation of pain (TSP), and offset analgesia (OA), which reflect some aspects of endogenous pain modulation. We included 15 men and 15 women (age, 31.5 [27.3–37.0], body mass index, 25.7 [24.4–27.1], Fitzpatrick skin typing, II: 20, III: 8, IV: 2). CPM, TSP, and OA were evaluated after a sham procedure (control session) and after acupuncture point stimulation (LI4 and LI10 on the non-dominant forearm) using linear polarized near-infrared light irradiation (LPNILI; wavelengths peaked at approximately 1000 nm, output: 1.4 W/cm2, spot diameter: 10 mm, spot size: 1.02 cm2, maximum temperature: 40.5 °C, pulse width: 1 s, frequency: 0.2 Hz) (PBM session). Differences in CPM, TSP, and OA between the two sessions were evaluated by the paired t-test and Fisher’s exact test (statistical significance: p < 0.05). Values indicate median [interquartile range]. LPNILI significantly increased CPM in all participants (control session: 12.1 [−4.5–37.4], PBM session: 23.9 [8.3–44.8], p < 0.05) and women (control session: 16.7 [−3.4–36.6], PBM session: 38.7 [24.6–52.1], p < 0.05). The CPM effect increment was significantly higher in women than in men (p = 0.0253). LPNILI decreased TSP in participants with higher TSP ratios (p = 0.0219) and increased OA in participants with lower OA scores (p = 0.0021). LPNILI enhanced endogenous pain modulation in healthy volunteers, particularly in women, as evaluated using CPM. CPM, TSP, and OA evaluations are potentially useful for discriminating PBM responders from non-responders.

Efficiency of pain inhibition and facilitation of fibromyalgia patients is not different from healthy controls: Relevance of sensitivity-adjusted test stimuli.

Pain is a dynamic phenomenon dependent on the balance of endogenous excitatory and inhibitory systems, which can be characterized by quantitative sensory testing. Many previous studies of pain modulatory capacity of patients with fibromyalgia syndrome (FM) have reported decreased pain inhibition or increased pain facilitation. This is the first study to assess pain modulation, including conditioned pain modulation (CPM) and temporal pain summation, in the same healthy control (HC) and FM participants. Only sensitivity-adjusted stimuli were utilized for testing of conditioned pain modulation (CPM) and temporal pain summation in 23 FM patients and 28 HC. All subjects received sensitivity-adjusted ramp-hold (sRH) during testing of pain facilitation (temporal summation) and pain inhibition (CPM). CPM efficacy was evaluated with test stimuli applied either concurrently or after application of the conditioning stimulus. Finally, the effects of CPM on pressure pain thresholds were tested. FM subjects required significantly less intense test and conditioning stimuli than HC participants to achieve standardized pain ratings of 50 ± 10 numerical rating scale (NRS) (p = 0.03). Using such stimuli, FM subjects' temporal pain summation and CPM efficacy was not significantly different from HC (all p > 0.05), suggesting similar pain facilitation and inhibition. Furthermore, the CPM efficacy of FM and HC participants was similar regardless of whether the test stimuli were applied during or after the conditioning stimulus (p > 0.05). Similar to previous studies, FM participants demonstrated hyperalgesia to heat, cold, and mechanical stimuli. However, using only sensitivity-adjusted stimuli during CPM and temporal summation testing, FM patients demonstrated similarly effective pain inhibition and facilitation than HC, suggesting that their pain modulation is not abnormal.

Sex-related differences in experimental pain sensitivity in subjects with painful or painless neuropathy after surgical repair of traumatic nerve injuries.

Sex-related influences represent a contributor to greater pain sensitivity and have a higher prevalence of many chronic pain conditions, including neuropathic pain (NP), among women. The aim was to analyze how differences in ongoing pain, experimental pain intensity, and conditioned pain modulation (CPM) relate to sex in subjects with neuropathy after traumatic nerve injuries. Endogenous pain modulation was compared between male (n = 77) and female (n = 55) subjects and between subjects with NP (female = 31, male = 39) and pain-free subjects with posttraumatic neuropathy (female = 24, male = 38). Conditioned pain modulation was assessed by pain ratings to pressure stimuli before and after a noxious conditioning stimulus (CS) conducted with one arm submerged in cold water (4°C) for 1 minute. Time of recovery (Time off) of pain intensity from peak VASmaxc after CS was recorded and compared between male and female patients. Greater ongoing pain intensity was found among female patients compared with male patients and more experimental pain after pressure and cold induced pain. Summing all groups together, women had 0.8 times higher odds (20%) of recovering sooner than men after CS (95% CI = 0.65-2.9). No differences in CPM, time off, and psychosocial variables were seen between female and male patients (P < 0.05). Our hypothesis for sex differences in endogenous pain modulation was only supported by a shorter after-sensation time after cold CS in female patients. No sex differences in the magnitude of CPM effect were identified. Increased pain intensity for experimental pain, in both neuropathic pain and neuropathy without pain, was found in female patients.

Allodynia, Hyperalgesia, (Quantitative) Sensory Testing and Conditioned Pain Modulation in Patients With Complex Regional Pain Syndrome Before and After Spinal Cord Stimulation Therapy

ObjectivesComplex regional pain syndrome (CRPS) is a chronic debilitating disease characterized by sensory abnormalities. Spinal cord stimulation (SCS) is an effective therapy for CRPS, but few studies have investigated the effects of SCS therapy on sensory characteristics. Therefore, this study investigated the effect of SCS on allodynia, hyperalgesia, electrical quantitative sensory testing (QST) parameters, and conditioned pain modulation (CPM) effect. Materials and MethodsThis study is part of a multicenter randomized controlled trial (ISRCTN 36655259). Patients with CRPS in one extremity and eligible for SCS were included. The outcome parameters allodynia (symptom and sign), hyperalgesia (symptom), sensory thresholds with QST, CPM effect, and pain scores were tested before and after three months of SCS (40-Hz tonic SCS). Both the CRPS-affected extremity and the contralateral, clinically unaffected extremity were used to test three sensory thresholds with electrical QST: current perception threshold (CPT), pain perception threshold (PPT), and pain tolerance threshold (PTT). The PTT also was used as a test stimulus for the CPM paradigm both before and after the conditioning ice-water test. Nonparametric testing was used for all statistical analyses. ResultsIn total, 31 patients were included for analysis. Pain, allodynia (sign and symptom), and hyperalgesia (symptom) were all significantly reduced after SCS therapy. On the unaffected side, none of the QST thresholds (CPT, PPT, and PTT) was significantly altered after SCS therapy. However, the CPT on the CRPS-affected side was significantly increased after SCS therapy. A CPM effect was present both before and after SCS. ConclusionsStandard 40-Hz tonic SCS significantly reduces pain, hyperalgesia, and allodynia in patients with CRPS. These findings suggest that SCS therapy should not be withheld from patients who suffer from allodynia and hyperalgesia, which contradicts previous findings derived from retrospective analysis and animal research.ISRCTN Registry: The ISRCTN registration number for the study is ISRCTN 36655259.

Mechanisms of chronic pain in inflammatory rheumatism: the role of descending modulation.

Persistent pain despite satisfactory disease treatment is frequent in rheumatoid arthritis (RA) and spondyloarthritis (Spa) and may result from specific changes in central pain processing. We assessed these mechanisms further by systematically comparing thermal pain thresholds and conditioned pain modulation (CPM) between patients with active RA or Spa and healthy controls. We included 50 patients with RA and 50 patients with Spa and 100 age-matched and sex-matched controls. Heat and cold pain thresholds (HPT-CPT) were measured on the dominant forearm, and CPM was assessed by applying conditioning stimuli (immersion in a cold-water bath) to one foot and the nondominant hand in 2 successive randomized sequences. Descending pain modulation was assessed as the difference in HPTs (in °C) before and after conditioning. Larger HPT differences (ie, a larger CPM effect) reflected more efficient descending inhibition. Potential associations between changes in CPM and clinical data, including disease activity, pain intensity, and psychological and functional variables, were systematically assessed. Heat pain threshold and cold pain threshold were similar in patients and controls. The mean CPM effect was significantly weaker in patients than that in controls for conditioning applied to either the foot (0.25°C ±2.57 vs 2.79°C ±2.31; P < 0.001) or the nondominant hand (0.57°C ±2.74 vs 2.68°C ±2.12; P < 0.001). The smaller CPM effect in patients was correlated with average pain intensity, but not with disease activity or other clinical characteristics, suggesting a significant pathophysiological role for changes in endogenous pain modulation in the mechanisms of chronic pain associated with inflammatory rheumatism.

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.

Diffuse noxious inhibitory controls and conditioned pain modulation: a shared neurobiology within the descending pain inhibitory system?

Diffuse noxious inhibitory controls and conditioned pain modulation: a shared neurobiology within the descending pain inhibitory system?

Conditioned pain modulation is not associated with thermal pain illusion.

Paradoxical sensations, known as thermal pain illusions, can be evoked by painful cold-heat pulse stimulation. They may provide diagnostic value; however, the possible interaction between conditioned pain modulation and thermal pain illusions has not been explored. The present study examined: (1) whether conditioned pain modulation could be induced by alternating tonic painful cold-heat pulse stimulation; and (2) whether the presence of thermal pain illusions during the conditioning stimulus influences the degree of conditioned pain modulation. This study was approved by the Ethics Committee of Meikai University (A1507). Conditioned pain modulation was provoked using alternating painful cold-heat pulses delivered at 20-s intervals applied to the forearm. Thermal pain illusions were qualitatively evaluated, and conditioned pain modulation was assessed quantitatively using the pressure pain threshold as a test stimulus. Differences in the conditioned pain modulation effect between the participants who experienced thermal pain illusions and those who did not were analysed using Student's t-test. A significant positive conditioned pain modulation effect (51.0±4.7%, overall effect) was detected. There was no significant difference in conditioned pain modulation between the participants who experienced thermal pain illusions and those who did not (44.3±6.0% and 55.5±6.8%, respectively; p=0.255). Conditioned pain modulation induced by alternating painful conditioning cold-heat pulse stimulation was identical during the conditioning stimulation in volunteers with and without thermal pain illusions. Conditioning cold-heat pulse stimulation is useful to evaluate conditioned pain modulation. Moreover, conditioned pain modulation is not influenced by the presence of thermal pain illusions, indicating partially different underlying supraspinal, neuronal networks.