Measurement Of Pain Threshold Research Articles

Pain sensitivity as a state marker and predictor for adolescent non-suicidal self-injury.

The pain analgesia hypothesis suggests that reduced pain sensitivity (PS) is a specific risk factor for the engagement in non-suicidal self-injury (NSSI). Consistent with this, several studies found reduced PS in adults as well as adolescents with NSSI. Cross-sectional studies in adults with borderline personality disorder (BPD) suggest that PS may (partially) normalize after remission or reduction of BPD symptoms. The objective of the present study was to investigate the development of PS over 1 year in a sample of adolescents with NSSI and to investigate whether PS at baseline predicts longitudinal change in NSSI. N = 66 adolescents who underwent specialized treatment for NSSI disorder participated in baseline and 1-year follow-up assessments, including heat pain stimulation for the measurement of pain threshold and tolerance. Associations between PS and NSSI as well as BPD and depressive symptoms were examined using negative binomial, logistic, and linear regression analyses. We found that a decrease in pain threshold over time was associated with reduced NSSI (incident rate ratio = 2.04, p = 0.047) and that higher pain tolerance at baseline predicted lower probability for NSSI (odds ratio = 0.42, p = 0.016) 1 year later. However, the latter effect did not survive Holm correction (p = 0.059). No associations between PS and BPD or depressive symptoms were observed. Our findings suggest that pain threshold might normalize with a decrease in NSSI frequency and could thus serve as a state marker for NSSI.

Evaluation of the segmental distribution of pain sensitivity among patients with central sensitization associated with chronic subacromial pain syndrome: A cross-sectional study

IntroductionPain sensitivity is the main finding of central sensitization (CS) and can occur in patients with chronic shoulder pain. However, there is limited evidence concerning the distribution of pain sensitivity in shoulders, forearms, and legs in patients with CS associated with chronic shoulder pain. The present study aimed to determine the distribution of pain sensitivity in patients with CS associated with chronic subacromial pain syndrome (SPS). MethodThis cross-sectional study included 58 patients with chronic SPS and CS (patient group) and 58 healthy participants (control group). The presence of CS was determined using the Central Sensitization Inventory (CSI). To determine the distribution of pain sensitivity, pressure pain threshold (PPT) measurements were performed from the shoulders, forearms, and legs. ResultsThere was no significant difference between the two groups in terms of sociodemographic data (p > 0.05). The patient group had a significantly higher CSI score (p < 0.001) and lower PPTs in all regions (p < 0.05) than the control group. Unlike the control group, the patient group had lower PPTs on the affected side for the shoulder [mean difference (MD) 95% confidence interval (CI): 1.2 (−1.7 to −0.6)], forearm [MD 95% CI: 1.1 (−1.7 to −0.6)], and leg [MD 95% CI: 0.9 (−1.4 to −0.3)] compared with the contralateral side (p < 0.001). ConclusionPain sensitivity is more pronounced in the affected shoulder and the forearm and leg located on this side than in those on the contralateral side in patients with CS associated with chronic SPS.

Efficacy of Dry Needling Therapy Versus IASTM on Myofascial Trigger Point in Patient with Neck Pain

Background: The background of the study is soft tissue mobilization and dry needling among neck pain subjects,which indirectly affect functional activity and pressure threshold for pain over the neck area.Purpose: To evaluate the effects of IASTM and dry needling therapy on myofascial trigger points in individualswith neck pain. And assess the effect of pain and functional outcomes by pressure algometer and NDI.Methods: Thirty participants were randomly assigned to the two groups the dry needling therapy (DNT)Group and Instrument assisted soft tissue mobilization (IASTM) Group. The pretest measures of pressure painthreshold and functional activity of the neck were assessed by the pressure algometer and the neck disabilityindex, respectively. The intervention DNT Group received dry-needling therapy, whereas the intervention IASTMGroup received IASTM for a duration of 4 weeks. The same tests were measured after 4 weeks of treatment aspost-test values.Result: A substantial difference between the NDT group and the IASTM group was also discovered (p = 0.001).The study showed that dry needling significantly impacts pressure pain threshold and functional activity in neckpain participants. Conclusion: The dry needling therapy effectively improved functional activity and reducedpressure and pain thresholds.&#x0D; Conclusion: Dry needling therapy has emerged as an effective therapeutic option for treating trigger points in theneck and relieving pain associated with them.

Association between central sensitivity syndrome and psychophysical factors in patients with masticatory myofascial pain.

This study explored the relationship between central sensitization symptoms, assessed using the Central Sensitization Inventory (CSI), and psychophysical factors in patients with chronic masticatory myofascial pain (MMP) transitioning from the acute to chronic stages. In this study, 23 patients with MMP and 22 healthy volunteers were assessed using psychophysical tests, including measurements of pressure pain threshold (PPT) and temporal summation of pain (TSP). Additionally, CSI scores were recorded to evaluate central sensitization symptoms. Patients with chronic MMP showed significantly lower PPT in all masticatory muscles and extratrigeminal areas compared with controls. However, there was no significant correlation between CSI scores and psychophysical test results in patients with MMP. The significant enhancement of TSP in patients with subchronic MMP suggests a potential role in the onset of myofascial pain. The main finding suggests that sub-chronic symptom patients show higher CSI scores despite no sensory testing changes, indicating that central sensitization possibly precedes observable symptoms.

Effect of spinal cord stimulation for thermal noxious stimulus pain threshold in Parkinson's disease

BackgroundParkinson's disease (PD)-related pain or PD pain is a frequent non-motor symptom and is treated with pharmacotherapy and non-pharmacologic therapies such as deep brain stimulation (DBS) and spinal cord stimulation (SCS). The mechanism of PD pain relief by DBS is thought to involve increased pain threshold to nociceptive stimulation, whereas the mechanism of SCS has not been elucidated. ObjectivePD pain relief by SCS may involve modulation of the pain thresholds in the spinal cord segments and supra-spinal actions. Therefore, we investigated the effect of SCS in patients who underwent SCS for intractable PD pain in the lower extremities by measuring pain thresholds to thermal nociceptive stimulation of the lower (leg) and upper (hand) parts of the stimulated spinal segment during SCS-off and SCS-on using quantitative sensory testing to determine the pain threshold. MethodsSeven PD patients with SCS in the lower thoracic spinal cord underwent measurements of cold sensory threshold, warm sensory threshold, cold pain threshold (CPT), and heat pain threshold (HPT). ResultsIn upper part of the stimulated spinal segment, CPT was significantly decreased during SCS-on compared to SCS-off (p < 0.01); whereas HPT was not significantly different. In lower part of the stimulated spinal segment, CPT was significantly increased during SCS-on compared to SCS-off (p < 0.05); and HPT was also increased (p < 0.05). ConclusionThis study shows that SCS raises the pain threshold to thermal nociception in PD patients. The primary mechanism of pain relief by SCS is thought to be segmental inhibition at the level of the stimulated spinal segments.

Further evaluation of inflammatory and non-inflammatory aspects of pain in rheumatoid arthritis patients.

A high discrepancy between the number of tender and swollen joints (e.g. ΔTSJ ≥ 7) has previously been used as an indication for the presence of changes in central mechanisms in patients with moderate-to-high disease activity. In this study, we explored whether the ΔTSJ can also be used to obtain insights into the underlying pain mechanisms in patients with on average well-controlled disease activity. A 2 year retrospective analysis of routinely obtained 28-joint DAS (DAS28) components was performed on 45 patients with low inflammatory activity at the group level. All patients underwent pressure pain threshold (PPT) and electrical pain threshold (EPT) measurements and completed four self-report questionnaires [short-form 36 (SF-36v2); central sensitization inventory (CSI); generalized pain questionnaire (GPQ); and the pain catastrophizing scale (PCS)]. Patients with a ΔTSJ ≥ 3 at least once in the past 2 years showed significantly lower EPT and PPT values and higher levels of pain and disability on the SF-36v2 compared with the ΔTSJ < 3 group. Furthermore, GPQ scores were significantly higher in those with ΔTSJ ≥ 3, while CSI and PCS scores were similar. These findings suggest that in patients in the ΔTSJ ≥ 3 group, mechanisms other than inflammation (only) underlie the pain. Moreover, our findings suggest that among the multiple potential underlying psychological mechanisms, pain catastrophizing (as measured by the PCS) and psychological hypervigilance (as measured by the CSI) do not play an important role. These findings could be useful in the clinical management of the patient. Depending on the dominant mechanism underlying the (persistent) pain, patients might respond differently to treatment.

The reliability of pressure pain threshold in individuals with low back or neck pain: a systematic review.

Low-back and neck pain affect a great number of individuals worldwide. The pressure pain threshold has the potential to be a useful quantitative measure of mechanical pain in a clinical setting, if it proves to be reliable in this population. The objectives of this systematic review are to: (1) analyze the literature evaluating the reliability of pressure pain threshold (PPT) measurements in the assessment of neck and low-back pain, (2) summarize the evidence from these studies, and (3) characterize the limitations of PPT measurement. Relevant literature from PubMed and the Web of Science electronic databases were screened in a 3-step process according to inclusion/exclusion criteria. Relevant studies were assessed for risk of bias using the Quality Appraisal of Reliability Studies (QAREL) tool, and results of all studies were summarized and tabulated. Of 922 citations identified, 11 studies were deemed relevant for critical appraisal, and 8 studies were deemed to have low risk-of bias. Intra-rater reliability, reported in all studies (n = 637) and inter-rater reliability, reported in 2 studies (n = 200) were consistently reported to be good to excellent (ICC 0.75-0.99 and ICC 0.81-0.90, respectively). Studies were also found to have significant variation in PPT measurement procedures. Though intra- and inter-rater reliability was found to be high in all studies, the variation in PPT measurement protocols could affect validity and absolute reliability. As such, it is recommended that standard guidelines be developed for clinical use.

The Relationship between Nociceptive Detection Thresholds and Pressure- and Electrical Pain Thresholds: An Explorative Study in Rheumatoid Arthritis Patients.

Recently, methods have been developed enabling the characterization of the nociceptive function at the detection threshold level by measuring nociceptive detection thresholds (NDTs), rather than at the level of the pain threshold via pain threshold (PT) measurements. Both NDT and PT measurements aim to characterize (parts of) the nociceptive system. To date it is unclear if, and if so to what extent, the two outcomes relate to one another. In this study, the primary aim is to explore the relationship between the two measures in patients with rheumatoid arthritis (RA). As secondary aim, we explore differences in NDT between these RA patients with age- and sex-matched healthy controls (HC) from a readily existing dataset. In total 46 RA patients have been recruited, whereby the pressure- (PPT; bilaterally at two locations) and electrical (EPT) pain threshold were evaluated, as well as the NDTs. Significant, positive correlations were found between the EPT and PPT (R=0.54-0.60), but not with the NDTs (R≤0.25). As compared to HC, higher NDTs were found in the RA group. As the presence of a statistically significant weak relationship can only be evaluated using a larger sample size, our results indicate that there is no moderate or stronger relation between PT and NDT outcomes. This implicates that the two outcomes are not strongly driven by the same (nociceptive) mechanism(s). Future research into NDTs and what factors and/or mechanisms affect the outcome, could yield relevant insights into how to use and interpret the results of this relatively new method.Clinical Relevance - The evaluation of nociceptive detection thresholds, in isolation or together with conventionally evaluated pain thresholds, might provide valuable and complementary insights into nociceptive (dis)function in man.

Pain intensity and pain sensitivity are not increased by a single session of high-intensity interval aerobic exercise in individuals with chronic low back pain: A randomized and controlled trial

BackgroundEvidence on the acute impact of high-intensity interval aerobic exercise on pain is scarce. This type of exercise might be perceived as increasing pain intensity and pain sensitivity negatively impacting adherence. More evidence on the acute effects of high-intensity interval aerobic exercise in individuals with low back pain (LBP) is needed. ObjectivesTo compare the acute effects of a single session of high-intensity interval aerobic exercise, continuous moderate-intensity aerobic exercise, and no exercise on pain intensity and pain sensitivity in patients with chronic non-specific LBP. DesignRandomized controlled trial with three arms. MethodParticipants were randomly assigned to one of three groups (i) continuous moderate-intensity aerobic exercise, ii) high-intensity interval aerobic exercise, and iii) no intervention. Measures of pain intensity and pressure pain threshold (PPT) at the lower back and at a distant body site (upper limb) were taken before and after 15 min of exercise. ResultsSixty-nine participants were randomized. A significant main effect of time was found for pain intensity (p = 0.011; η2p = 0.095) and for PPT at the lower back (p < 0.001; η2p = 0.280), but not a time versus group interaction (p > 0.05). For PPT at the upper limb, no main effect of time or interaction was found (p > 0.5). ConclusionsFifteen minutes of high-intensity interval aerobic exercise does not increase pain intensity or pain sensitivity compared to both moderate-intensity continuous aerobic exercise and no exercise, suggesting that high-intensity interval aerobic exercise can be used in clinical practice and patients reassured that it is unlikely to increase pain.

Preoperative pain sensitivity predicts postoperative pain severity and analgesics requirement in lumbar fusion surgery – a prospective observational study

BACKGROUND CONTENTThe goal of postoperative pain management is to facilitate the patient's return to normal activity and decrease the detrimental effects of acute postsurgical pain. In order to provide more tailored and successful pain treatment, it is necessary to identify individuals who are at a high risk of experiencing severe postoperative pain. The most precise way to assess pain sensitivity is by determining the pressure pain threshold and heat pain threshold by objective methods using a digital algometer and neurotouch respectively. PURPOSEThe primary aim of the study is to assess the preoperative pain threshold and its influence on postoperative pain severity and analgesics requirements in patients undergoing lumbar fusion surgeries. STUDY DESIGNProspective, observational study. PATIENT SAMPLESixty patients requiring a single-level lumbar fusion surgery. OUTCOME MEASURESPostoperative pain intensity and the amount of postoperative analgesics consumption. METHODSIn our patients, preoperative pain sensitivity was assessed by pressure pain threshold measurements with the help of a digital algometer, and heat pain threshold using a neurotouch instrument. In addition, pain sensitivity questionnaires (PSQ) were used in all our patients to determine pain sensitivity. Preoperative psychosocial and functional assessments were performed by Hospital anxiety-depression scores (HADS), and Oswestry disability index (ODI) respectively. Preoperative visual analog scale (VAS) score was determined at three instances of needle prick (phlebotomy, glucometer blood sugar, and intradermal antibiotic test dose) and during the range of movements of the lumbar spine region. Postoperative VAS score and postoperative breakthrough analgesic requirements were recorded in all of these patients from day 0 to day 3. RESULTSThe average age of the patients was 51.11±13.467 years and 70% were females. Females had lower mean algometry values (72.14±7.56) compared to males (77.34±6.33). Patients with higher HADS (p<.0016), higher PSQ (p<.001), higher ODI scores(p<.001), and female gender significantly correlated with a lower algometer average indicating high pain sensitivity. Patients with lower preoperative VAS scores and with higher neurotouch scores showed lower postoperative VAS scores at different time periods. Preoperative VAS scores, algometer average scores, neurotouch scores, and HADS scores were considered as independent variables (predictors) for postoperative VAS at 6 hours period. By the multivariate analysis, factors like preoperative VAS scores, algometer average scores, and HADS scores were statistically significant (p<.05). There was a significant correlation between algometer average scores (p<.001) with the breakthrough analgesics. CONCLUSIONPreoperative assessment of pain sensitivity can predict postoperative analgesic requirements and aid in recovery. Patients with a lower pain threshold should be counseled preoperatively and also receive a better titration of analgesics perioperatively.

Comparison of the Nerve Regeneration Capacity and Characteristics between Sciatic Nerve Crush and Transection Injury Models in Rats

ObjectiveTo provide useful information for selecting the most appropriate peripheral nerve injury model for different research purposes in nerve injury and repair studies, and to compare nerve regeneration capacity and characteristics between them. MethodsSixty adult SD rats were randomly divided into two groups and underwent crush injury alone (group A, n = 30) or transection injury followed by surgical repair (group B, n = 30) of the right hind paw. Each group was subjected to the CatWalk test, gastrocnemius muscle evaluation, pain threshold measurement, electrophysiological examination, retrograde neuronal labeling, and quantification of nerve regeneration before and 7, 14, 21, and 28 days after injury. ResultsGait analysis showed that the recovery speed in group A was significantly faster than that in group B at 14 days. At 21 days, the compound muscle action potential of the gastrocnemius muscle in group A was significantly higher than that in group B, and the number of labeled motor neurons in group B was lower than that in group A. The number of new myelin sheaths and the g-ratio were higher in group A than in group B. There was a 7-day time difference in the regeneration rate between the two injury groups. ConclusionThe regeneration of nerve fibers was rapid after crush nerve injury, whereas the transection injury was relatively slow, which provides some ideas for the selection of clinical research models.

Resting-state neural mechanisms of capability for suicide and their interaction with pain – A CAN-BIND-05 Study

BackgroundSuicidal ideation is highly prevalent in Major Depressive Disorder (MDD). However, the factors determining who will transition from ideation to attempt are not established. Emerging research points to suicide capability (SC), which reflects fearlessness of death and increased pain tolerance, as a construct mediating this transition. This Canadian Biomarker Integration Network in Depression study (CANBIND-5) aimed to identify the neural basis of SC and its interaction with pain as a marker of suicide attempt. MethodsMDD patients (n = 20) with suicide risk and healthy controls (n = 21) completed a self-report SC scale and a cold pressor task measuring pain threshold, tolerance, endurance, and intensity at threshold and tolerance. All participants underwent a resting-state brain scan and functional connectivity was examined for 4 regions: anterior insula (aIC), posterior insula (pIC), anterior mid-cingulate cortex (aMCC) and subgenual anterior cingulate cortex (sgACC). ResultsIn MDD, SC correlated positively with pain endurance and negatively with threshold intensity. Furthermore, SC correlated with the connectivity of aIC to the supramarginal gyrus, pIC to the paracingulate gyrus, aMCC to the paracingulate gyrus, and sgACC to the dorsolateral prefrontal cortex. These correlations were stronger in MDD compared to controls. Only threshold intensity mediated the correlation between SC and connectivity strength. LimitationsResting-state scans provided an indirect assessment of SC and the pain network. ConclusionsThese findings highlight point to a neural network underlying SC that is associated with pain processing. This supports the potential clinical utility of pain response measurement as a method to investigate markers of suicide risk.

The effects of high-definition transcranial direct current stimulation on pain modulation and stress-induced hyperalgesia.

The dorsolateral prefrontal cortex (DLPFC) has been implicated in the modulation of pain-related signals. Given this involvement, manipulation of the DLPFC through transcranial direct current stimulation (tDCS) may influence internal pain modulation and decrease pain sensitivity. Acute stress is also thought to affect pain, with increased pain sensitivity observed following the presentation of an acute stressor. A total of 40 healthy adults (50% male), ranging in age from 19 to 28 years (M = 22.13, SD = 1.92), were randomly allocated to one of two stimulation conditions (active and sham). High-definition tDCS (HD-tDCS) was applied for 10min at 2mA, with the anode placed over the left DLPFC. Stress was induced after HD-tDCS administration using a modified version of the Trier Social Stress Test. Pain modulation and sensitivity were assessed through the conditioned pain modulation paradigm and pressure pain threshold measurements, respectively. Compared to sham stimulation, active stimulation produced a significant increase in pain modulation capacity. No significant change in pain sensitivity and stress-induced hyperalgesia was observed following active tDCS. This research shows novel evidence that anodal HD-tDCS over the DLPFC significantly enhances pain modulation. However, HD-tDCS had no effect on pain sensitivity or stress-induced hyperalgesia. The observed effect on pain modulation after a single dose of HD-tDCS over the DLPFC is a novel finding that informs further research into the utility of HD-tDCS in the treatment of chronic pain by presenting the DLPFC as an alternative target site for tDCS-induced analgesia.

The Importance of Personality Traits, Optimism and Quality of Life for Pain Threshold and Pain Tolerance in the Elderly

With increasing age, the frequency of chronic pain increases compared to acute pain. This is due to structural and functional changes caused by ageing of the nervous system. The aim of this study was to investigate relationships between personality traits, optimism, quality of life, and subjective assessment of pain measured experimentally with an algometer and clinically with the Visual Analoque Scale (VAS). In the group of 133 seniors (61-86 years; 78% women), we used an algometer to measure pain threshold and tolerance, the VAS scale to assess subjective intensity, and standardized questionnaires (EPQ-R(s), LOTR, SWLS) to measure psychological variables. Extraversion was found to promote both higher pain threshold and higher pain tolerance, whereas pain tolerance was negatively correlated with neuroticism. Higher severity of the psychotic trait was associated with more intense subjective pain experience. Optimism and overall quality of life were not associated with any pain measures. A better understanding of the personality correlates of pain perception could support a more accurate tailoring of pain management in elderly patients.

A novel thermoelectric device integrated with a psychophysical paradigm to study pain processing in human subjects

IntroductionCerebral projections of nociceptive stimuli are of great interest as targets for neuromodulation in chronic pain. To study cerebral networks involved in processing noxious stimuli, researchers often rely on thermo-nociception to induce pain. However, various limitations exist in many pain-inducing techniques, such as not accounting for individual variations in pain and trial structure predictability. MethodsWe propose an improved and reliable psychometric experimental method to evaluate human nociceptive processing to overcome some of these limitations. The developed testing paradigm leverages a custom-built, open-source, thermoelectric device (TED). The device construction and hardware are described. A maximum-likelihood adaptive algorithm is integrated into the TED software, facilitating individual psychometric functions representative of both hot and cold pain perception. In addition to testing only hot or cold thresholds, the TED may also be used to induce the thermal grill illusion (TGI), where the bars are set to alternating warm and cool temperatures. ResultsHere, we validated the TED's capability to adjust between different temperatures and showed that the device quickly and automatically changes temperature without any experimenter input. We also validated the device and integrated psychometric pain task in 21 healthy human subjects. Hot and cold pain thresholds (HPT, CPT) were determined in human subjects with <1 °C of variation. Thresholds were anticorrelated, meaning a volunteer with a low CPT likely had a high HPT. We also showed how the TED can be used to induce the TGI. ConclusionThe TED can induce thermo-nociception and provide probabilistic measures of hot and cold pain thresholds. Based on the findings presented, we discuss how the TED could be used to study thermo-nociceptive cerebral projections if paired with intracranial electrode monitoring.

Dominance-submissiveness cues modulate pain threshold for mechanical pressure.

Acute pain sensation is an inherently negative but adaptive experience; however, research on pain sensitivity shows that simple contextual cues can effectively attenuate the pain. In this study, we sought to investigate how dominance cues, manipulated as vertical spatial (i.e., height) distance between participants and experimenter, affect participants' pain sensitivity. Positioning participants in a spatially higher position relative to the experimenter was aimed to induce a feeling of dominance in participants. Conversely, a feeling of submissiveness was induced by placing the experimenter in a spatially higher position. In addition, we examined the role of dominance cues with respect to participants' and experimenters' gender. Two separate studies were conducted-Study 1 with a male experimenter measuring pain threshold in female and male participants (N = 137), and Study 2 with a female experimenter conducting pain measurement in a new sample of female and male participants (N = 122). The results of both studies demonstrated that participants in a dominant position reported a higher pain threshold relative to participants in a submissive position. Male participants had a higher pain threshold in both studies; however, Study 1 revealed a significant interaction of dominance manipulation and participant's gender, with the effect of dominance cues being larger in men.

Central sensitization in osteoarthritic knee pain: A cross-sectional study.

The aim of this study was to investigate central sensitization and associated factors in knee osteoarthritis (OA) patients and compare them with rheumatoid arthritis (RA) patients and healthy controls. This cross-sectional study was conducted with 125 participants (7 males, 118 females; mean age: 57.2±8.2 years; range, 45 to 75 years) between January 2017 and December 2018. Sixty-two patients with symptomatic knee OA, 32 RA patients with knee pain, and 31 healthy controls constituted the participants. Central sensitization was investigated with the Central Sensitization Inventory (CSI) and pressure pain threshold (PPT) measurements. Pain, functional status, and psychosocial features were assessed with self-reported questionnaires. The OA and RA groups had significantly lower PPT values at local, peripheral, and remote regions compared to the healthy controls. Pressure hyperalgesia was shown at the knee with a 43.5% prevalence, 27.4% at the leg, and 8.1% at the forearm of OA patients. Pressure hyperalgesia was present at the knee, leg, and forearm in 37.5%, 25%, and 9.4% of RA patients, respectively. Pressure pain threshold values, CSI scores, frequency of pressure hyperalgesia, and frequency of central sensitization according to the CSI were not statistically different between the OA and RA groups. Psychosocial features and structural damage were not correlated with PPT values in the OA group. The severity of chronic pain and functional status may be the clinical clues to recognizing patients with central sensitization since local joint damage does not play a direct role in the etiopathogenesis of central sensitization in OA patients and severe pain persisting in the chronic process is associated with central sensitization regardless of the pathogenesis.

Advanced glycation end-products are associated with diabetic neuropathy in young adults with type 1 diabetes.

Aims/hypothesisAdvanced glycation end-products (AGEs) may contribute to the development of diabetic neuropathy. In young adults with type 1 diabetes, we aimed to investigate the association between AGEs and cardiovascular autonomic neuropathy (CAN) and distal symmetric polyneuropathy (DSPN).MethodsThis cross-sectional study comprised 151 young adults. CAN was assessed by cardiovascular autonomic reflex tests; lying-to-standing test, deep breathing test (E/I), Valsalva manoeuvre, and heart rate variability indices; and the mean square of the sum of the squares of differences between consecutive R-R intervals and standard deviation of normal-to-normal intervals (SDNN), high- (HF) and low-frequency (LF) power, total frequency power, and the LF/HF ratio. DSPN was assessed by light touch, pain and vibration perception threshold (VPT), neuropathy questionnaires, and objective measures. AGEs were analysed in four groups using z-scores adjusted for relevant confounders and multiple testing: i) “glycolytic dysfunction”, ii) “lipid peroxidation”, iii) “oxidative stress”, and iv) “glucotoxicity”.ResultsA higher z-score of “glycolytic dysfunction” was associated with higher VPT (4.14% (95% CI 1.31; 7.04), p = 0.004) and E/I (0.03% (95% CI 0.01; 0.05), p = 0.005), “lipid peroxidation” was associated with higher LF/HF ratio (37.72% (95% CI 1.12; 87.57), p = 0.044), and “glucotoxicity” was associated with lower SDNN (−4.20% (95% CI −8.1416; −0.0896), p = 0.047). No significance remained after adjustment for multiple testing.Conclusions/interpretationsIn young adults with type 1 diabetes, increased levels of AGEs involving different metabolic pathways were associated with several measures of CAN and DSPN, suggesting that AGEs may play a diverse role in the pathogeneses of diabetic neuropathy.

Effect of single end-range and not end-range Maitland mobilization on pressure pain threshold and functional measures in knee osteoarthritis: randomised, controlled clinical trial.

Hyperalgesia is attributed to peripheral and central sensitization in knee osteoarthritis (OA). Pressure pain threshold (PPT) is a relevant method for evaluating pain sensitivity in knee OA. The effect of end-range and not end-range Maitland mobilization for certain time-period on pain sensitivity has not been investigated in knee OA. The aim of this study was to investigate the effect of end-range and not end-range Maitland mobilization compared to sham manual therapy technique on PPT and functional measures. Randomised, controlled clinical trial. Outpatient setting. Sixty-six patients with mild-to-severe knee OA. Twenty-one patients (N.=21) received end-range Maitland mobilization (EMGr), twenty patients (N.=20) received not end-range Maitland mobilization (nEMGr) and twenty-two patients (N.=22) received sham manual therapy technique (CG). All interventions were performed once. Evaluation was conducted pre-, postintervention and on the following consecutive second days within a 6-day period. Outcomes were local and distant PPT, Timed Up and Go Test (TUG) and strength of passive resistance of knee at onset of pain. Local and distant PPT increased, TUG time and strength of passive resistance decreased immediately, local and distant PPT remained decreased in 6-day and 4-day period, TUG time remained decreased in 6-day period in EMGr (all changes P≤0.017). Local PPT increased immediately compared to baseline in nEMGr. In between group comparison, increase of local, distant PPT and strength of passive resistance endures on 2nd day, 4th day and postintervention, respectively, in EMGr compared to CG. EMGr compared to nEMGr presented significant difference on 6th day and 4th day in local and distant PPT, respectively (all changes P≤0.021). NEMGr presented no significant difference compared to CG on either follow-up. Single end-range Maitland mobilization is effective immediately and in 4-day period on pain sensitization and immediately on physical function compared to not end-range Maitland mobilization and sham manual therapy technique in knee OA. Based on the present results, applying end-range Maitland mobilization is suggested on every second day to maintain alleviation of pain sensitization and increasing passive knee joint mobility effectively in knee OA.

Thermal grill illusion of pain in patients with chronic pain: a clinical marker of central sensitization?

The thermal grill illusion of pain (TGIP) is a paradoxical burning pain sensation elicited by the simultaneous application of innocuous cutaneous warm and cold stimuli with a thermode ("thermal grill") consisting of interlaced heated and cooled bars. Its neurophysiological mechanisms are unclear, but TGIP may have some mechanisms in common with pathological pain, including central sensitization in particular, through the involvement of N-methyl- d -aspartate receptors. However, few studies have investigated TGIP in patients with chronic pain and its clinical relevance is uncertain. We hypothesized that the TGIP would be increased in comparison with controls in patients with fibromyalgia or irritable bowel syndrome, which are regarded as typical "nociplastic" primary pain syndromes related to changes in central pain processing. We compared the sensations elicited by a large range of combinations of temperature differentials between the warm and cold bars of a thermal grill applied to the hand between patients with fibromyalgia (n = 30) or irritable bowel syndrome (n= 30) and controls (n = 30). The percentage of TGIP responses and the intensity and unpleasantness of TGIP were significantly greater in patients than controls. Furthermore, positive correlations were found between TGIP intensity and clinical pain intensity and between TGIP intensity and the cold pain threshold measured on the hand. These results are consistent with our working hypothesis of shared mechanisms between TGIP and clinical pain mechanisms in patients with nociplastic chronic pain syndromes and suggest that TGIP might represent a clinical marker of central sensitization in these patients.