Conditioned Pain Modulation Response Research Articles

Restoration of normal central pain processing following manual therapy in nonspecific chronic neck pain.

To determine if a 4-week manual therapy treatment restores normal functioning of central pain processing mechanisms in non-specific chronic neck pain (NSCNP), as well as the existence of a possible relationship between changes in pain processing mechanisms and clinical outcome. Cohort study. Sixty-three patients with NSCNP, comprising 79% female, with a mean age of 45.8 years (standard deviation: 14.3), received four treatment sessions (once a week) of manual therapy including articular passive mobilizations, soft tissue mobilization and trigger point treatment. Pressure pain thresholds (PPTs), conditioned pain modulation (CPM) and temporal summation of pain (TSP) were evaluated at baseline and after treatment completion. Therapy outcome was measured using the Global Rating of Change Scale (GROC), the Neck disability Index (NDI), intensity of pain during the last 24 hours, Tampa Scale of Kinesiophobia (TSK) and Pain Catastrophizing Scale (PCS). Two sets of generalized linear mixed models with Gaussian response and the identity link were employed to evaluate the effect of the intervention on clinical, psychological and psychophysical measures and the association between psychophysical and clinical outcomes. Following treatment, an increased CPM response (Coefficient: 0.89; 95% credibility interval = 0.14 to 1.65; P = .99) and attenuated TSP (Coefficient: -0.63; 95% credibility interval = -0.82 to -0.43; P = 1.00) were found, along with amelioration of pain and improved clinical status. PPTs at trapezius muscle on the side of neck pain were increased after therapy (Coefficient: 0.22; 95% credibility interval = 0.03 to 0.42; P = .98), but not those on the contralateral trapezius and tibialis anterior muscles. Only minor associations were found between normalization of TSP/CPM and measures of clinical outcome. Clinical improvement after manual therapy is accompanied by restoration of CPM and TSP responses to normal levels in NSCNP patients. The existence of only minor associations between changes in central pain processing and clinical outcome suggests multiple mechanisms of action of manual therapy in NSCNP.

The Effect of Myofascial Stretching on Mechanical Nociception and Contributing Neural Mechanisms

Myofascial stretching is often prescribed in the management of musculoskeletal pain. However, the neural mechanisms contributing to a decrease in pain are unknown. Stretching produces a sensation that may act as a conditioning stimulus in a conditioned pain modulation response. The purpose of this study was to compare immediate changes in pressure pain thresholds (PPTs) during a low-intensity stretch, moderate-intensity stretch, and cold water immersion task. A secondary purpose was to examine if personal pain sensitivity and psychological characteristics were associated with the responses to these interventions. Twenty-seven (27) healthy participants underwent a cross-over study design in which they completed a cold water immersion task, upper trapezius stretch to the onset of the stretch sensation, and a moderate-intensity stretch. A significant condition x time effect was observed (F (8,160) = 2.85, p < 0.01, partial eta2 = 0.13), indicating reductions in pain sensitivity were significantly greater during a cold water immersion task compared to moderate-intensity stretching at minutes two and four. Widespread increases in heat pain threshold and lower pain-related anxiety were moderately correlated with the response to the cold water immersion task but not stretching. Moderate-intensity stretching may not elicit a conditioned pain modulation response possibly because the stretch was not intense enough to be perceived as painful.

Abnormalities of the Descending Inhibitory Nociceptive Pathway in Functional Motor Disorders.

Pain is a common disabling non-motor symptom affecting patients with functional motor disorders (FMD). We aimed to explore ascending and descending nociceptive pathways with laser evoked potentials (LEPs) in FMD. We studied a "bottom-up and top-down" noxious paradigm applying a conditioned pain modulation (CPM) protocol and recorded N2/P2 amplitude in 21 FMD and 20 controls following stimulation of both right arm and leg at baseline (BS) (bottom-up), during heterotopic noxious conditioning stimulation (HNCS) with ice test (top-down) and post-HNCS. We found a normal ascending pathway, but reduced CPM response (lower reduction of the N2/P2 amplitude) in FMD patients, by stimulating both upper and lower limbs. The N2/P2 amplitude ratio*100 (between the HNCS and BS) was significantly higher in patients with FMD than HC. Our results suggest that pain in FMD possibly reflects a descending pain inhibitory control impairment, therefore, providing a novel venue to explore the pathophysiology of pain in FMD. © 2024 International Parkinson and Movement Disorder Society.

The association between conditioned pain modulation and psychological factors in people with chronic spinal pain: A systematic review

Chronic spinal pain has negative effects on physical and mental well-being. Psychological factors can influence pain tolerance. However, whether these factors influence descending modulatory control mechanisms measured by conditioned pain modulation (CPM) in people with chronic spinal pain is unclear. This systematic review investigated the association between CPM response and psychological factors in people with chronic spinal pain. Published and unpublished literature databases were searched from inception to 23rd October 2023 included MEDLINE, EMBASE, CINAHL, and PubMed. Studies assessing the association between CPM response and psychological factors in people with chronic spinal pain were eligible. Data were pooled through meta-analysis. Methodological quality was assessed using the AXIS tool and the certainty of evidence measured through GRADE. From 2172 records, seven studies ( n = 598) were eligible. Quality of included studies was moderate. There was very low certainty of evidence that depression ( r = 0.01 [95% CI −0.10 to 0.12], I2 = 0%), and anxiety ( r = −0.20 [95% CI −0.56 to 0.16], I2 = 84%), fear avoidance ( r = −0.10 [95% CI −0.30 to 0.10], I2 = 70%) had no statistical associations with CPM responder status. Higher pain catastrophising was associated with CPM non-responder status (r = −0.19; 95% CI: −0.37 to −0.02; n = 545; I2: 76%) based on a very low certainty of evidence measured by GRADE. There is currently limited available evidence demonstrating an association between CPM response and psychological factors for people with chronic pain. Managing an individual’s chronic pain symptoms irrespective of comorbid psychological distress, should continue until evidence offer insights that more targeted interventions are needed.

Subgrouping of facilitatory or inhibitory conditioned pain modulation responses in patients with chronic knee pain. Explorative analysis from a multicentre trial.

Facilitatory and inhibitory conditioned pain modulation (CPM) responses are observed in healthy volunteers and chronic pain patients, but the clinical implications for phenotyping are unknown. This study aimed to subgroup and compare chronic knee pain patients according to their CPM responses. This explorative, cross-sectional study included 127 patients with chronic knee pain (osteoarthritis or following total knee arthroplasty). Individual CPM responses were categorized as facilitatory (test stimuli pain intensity increased when conditioning stimuli were applied), as inhibitory (test stimuli pain intensity decreased) or as no change (defined as less than 5.3% change in pain intensity). Outcomes were clinical pain intensities, temporal summation, widespread pain, self-reported physical function, PainDETECT questionnaire and Pain Quality Assessment Scale. Data were analysed as comparisons between the inhibitory and the facilitatory groups and using multivariate linear regression models. Fifty-four patients had facilitatory CPM responses, 49 had inhibitory CPM responses, and 24 showed no change in CPM response. A between-group difference was observed for self-reported physical function, with the facilitatory CPM group reporting better function (54.4 vs. 46.0, p = 0.028) and the facilitatory CPM group reported more deep pain sensations (3.2 vs. 2.0, p = 0.021). The remaining outcomes showed no between-group differences. Higher clinical pain intensity and facilitated temporal summation were associated in the facilitated CPM group but not in the inhibitory CPM group. These explorative findings indicated that quantitative clinical and experimental differences exist between facilitatory or inhibitory CPM responses in a chronic knee pain patient population. Differences in patients' CPM responses should be further investigated to unravel possible clinical importance. Our findings confirm that conditioned pain modulation consist of inhibitory and facilitatory responders among a patient population with chronic knee pain. This explorative study indicates that patients with either facilitatory or inhibitory conditioned pain modulation could exhibit differences in pain outcomes. Subgrouping of chronic pain patients depending on individual conditioned pain modulation responses could be considered in phenotyping patients prior to inclusion in clinical trials or used for personalizing the management regime.

Harnessing the conditioned pain modulation response in migraine diagnosis, outcome prediction, and treatment-A narrative review.

To present the potential use and relevance of the conditioned pain modulation (CPM) response to migraine diagnosis, outcome prediction, and treatment. The CPM response is a widely used laboratory test to examine inhibitory pain modulation capabilities. This narrative review summarizes and synthesizes the findings on the CPM response in patients with migraine. For diagnosis, we summarized the studies comparing CPM responses between patients with migraine and individuals without migraine or with other headache syndromes, as well as between patients with subtypes of migraine. For prediction, we summarized the studies utilizing the CPM response to predict migraine outcome, such as response to interventions. For treatment, we described a device that utilizes the CPM response for acute and preventative migraine treatment. In addition, we suggest the requirements needed for the CPM response to be used for migraine diagnosis, outcome prediction, and treatment. Although more research is needed, the CPM response could be a useful tool for improving migraine management.

Does Exercise-Induced Hypoalgesia Depend on Exercise Duration?

Acute physical activity is assumed to lead to exercise-induced hypoalgesia (EIH). Yet, little research has been conducted dealing with the influence of exercise duration on EIH. The aim of this study was to investigate the effects of three different exercise durations using the same intensity compared to a control session on EIH. A total of 36 participants conducted three different exercise sessions on a bicycle ergometer for 30, 45, and 60 min, respectively, in addition to a passive control session. The intensity was set to 75% of the individual's VO2max. Pre and post exercise, pain sensitivity was measured employing pressure pain thresholds (PPT) at the elbow, knee, and ankle joints, as well as the sternum and forehead. In addition, the conditioned pain modulation (CPM) response was conducted pre and post exercise. The results reveal that the exercises neither led to any changes in PPT measured at any landmark nor induced any CPM response effects. These results do not confirm the hypoalgesic effects usually observed after exercise. The reasons explaining these results remain rather elusive but might be explained by the low intensities chosen leading to a milder release of pain inhibiting substances, the landmarks employed for PPT measurements, or potential non-responsiveness of participants.

Exercise-Induced Hypoalgesia Following Proprioceptive Neuromuscular Facilitation and Resistance Training Among Individuals With Shoulder Myofascial Pain: Randomized Controlled Trial.

Various exercises can attenuate pain perception in healthy individuals and may interact with the descending pain modulation in the central nervous system. However, the analgesic effects of exercise in patients with myofascial pain can be disrupted by the pathological changes during chronic pain conditions. Thus, the exercises targeted on the facilitation of the sensory-motor interaction may have a positive impact on the restoration of the descending pain modulation and the analgesia effects. This paper estimates the effect of proprioceptive neuromuscular facilitation (PNF) and resistance training on exercise-induced hypoalgesia (EIH) and conditioned pain modulation (CPM) among patients with myofascial pain syndrome. A total of 76 female patients with myofascial pain syndrome (aged 18-30 years), with the pain in the upper trapezius and a visual analog scale score of greater than 30/100 mm, were enrolled in the study. Participants were randomly assigned into 3 intervention groups, including isometric (n=18, 24%), isotonic (n=19, 25%), and PNF (n=20, 26%) exercises, as well as 1 control group (n=19, 25%) with no intervention. Pressure pain threshold and the CPM responses at the myofascial trigger point, arm, and leg sites were assessed before and after the exercise session. The effective EIH response was reflected in the improvement of pressure pain thresholds. There was an increase in pressure pain thresholds and CPM responses at trigger point (P<.001 and P<.001), arm (P<.001 and P<.001), and leg sites (P<.001 and P=.03) in participants who performed PNF and isotonic exercise, while the isometric exercise only increased pressure pain thresholds at leg sites (P=.03). Compared with the control group, both the isotonic (P=.02) and PNF (P<.001) groups showed greater EIH responses at the trigger points. In comparison to the control group, only the PNF exercise (P=.01) significantly improved pressure pain thresholds and CPM responses at arm and leg sites compared to the control group. PNF, isotonic, and isometric exercises could lead to local and global EIH effects. The improvement in CPM response following PNF and isotonic exercises suggested that the EIH mechanisms of different resistance exercises may be attributed to the enhancement of the endogenous pain modulation via the motor-sensory interaction from the additional eccentric and dynamic muscle contraction. Chinese Clinical Trial Registry ChiCtr202111090819166165; https://tinyurl.com/2ab93p7n.

Clusters of facilitatory and inhibitory conditioned pain modulation responses in a large sample of children, adolescents, and young adults with chronic pain.

When investigating the role of facilitatory and inhibitory pain mechanisms such as conditioned pain modulation (CPM) and temporal summation of pain (TSP), it is important to take both into consideration in a single experimental model to provide the most information on subgroups of patients. Therefore, the objective of this study was to identify subgroups in a large population of pediatric patients with chronic pain based on their facilitatory and inhibitory pain mechanisms and compare them with control subjects. Five hundred twenty-one female subjects and 147 male subjects between 8 and 21 years old underwent a CPM assessment using a 2-minute tonic noxious heat stimulation as the test stimulus and a 2-minute cold-pressor task (CPT) (12°C) as the conditioning stimulus. The best partition of clusters of patients was 3 clusters accounting for 27.15% of the total variation in the data. Cluster 1 (n = 271) was best characterized by high pain intensity during the CPT, lack of TSP during the test stimuli, and efficient inhibitory CPM. Cluster 2 (n = 186) was best characterized by low pain intensity during the CPT, lack of TSP during the test stimuli, and efficient inhibitory CPM. Cluster 3 (n = 151) was best characterized by high pain intensity during the CPT, presence of TSP during the test stimuli, and inefficient inhibitory CPM. A single thermal CPM experimental design can identify combinations of facilitatory and inhibitory pain modulation responses. Findings from the current study add to the literature by describing different clinical phenotypes of central pain mechanisms of youth with chronic pain.

Symptomatic but not Asymptomatic COVID-19 Impairs Conditioned Pain Modulation in Young Adults

Pain is a common symptom reported in COVID-19 patients. Impaired endogenous pain-modulatory mechanisms such as conditioned pain modulation (CPM), and exercise-induced hypoalgesia (EIH) have been found in chronic pain conditions but is often overlooked in acute conditions that evoke painful symptoms, such as COVID-19. The purpose was to compare pressure-pain sensitivity, CPM, and EIH function among individuals who previously had COVID-19, both symptomatically and asymptomatically, and a healthy control group. Pressure pain thresholds of 59 participants were assessed in the forearm and leg using a pressure algometer before and after 1) submersion of their dominant foot in cold water (2°C) for 1min; and 2) isometric knee extension performed to task-failure at 25% of their maximal contraction. The CPM response was attenuated in individuals who were infected with symptomatic COVID-19 (N = 26) compared to asymptomatic COVID-19 (N = 13) in arm (-1.0% ± 20.3 vs 33.3% ± 26.2; P < .001) and leg (12.8% ± 22.0 vs 33.8% ± 28.2; P = .014) and compared to controls (N = 20) in arm only (-1.0% ± 26.2 vs 23.4% ± 28.2; P = .004). The EIH response was not different between groups. CPM was impaired in individuals who had symptomatic COVID-19, which may have long-term implications on pain modulation. PerspectiveThis study reveals that CPM was impaired in individuals who had symptomatic COVID-19 during the first wave of COVID-19, pre vaccine. These findings present a preliminary motive to study the long-term implications of COVID-19 and its effects on pain modulation.

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?

Exploring pain mechanisms in hypermobile Ehlers-Danlos syndrome: A case-control study.

The hypermobile type of Ehlers-Danlos syndrome (hEDS) is a heritable connective tissue disorder, associated with joint hypermobility and prominent chronic pain. Because experimental pain testing in hEDS is scarce, the underlying mechanisms are still poorly understood. The present study assesses endogenous pain facilitation and pain inhibition in hEDS, using a protocol for temporal summation of pain (TSP), conditioned pain modulation (CPM) and exercise-induced hypoalgesia (EIH). Twenty women with hEDS and 20 age-matched healthy controls participated. After evaluating thermal and mechanical pain thresholds (PPT), TSP was assessed using 10 repetitive painful pressure stimuli. CPM was provoked using pressure as the test stimulus and hand immersion in hot water (46°) as the conditioning stimulus. EIH was assessed after a submaximal cycling protocol. The hEDS group demonstrated reduced PPTs and showed significantly more TSP after repeated painful stimuli than the control group. In comparison to the healthy control group, the hEDS group demonstrated significantly less EIH at the quadriceps test location. At the trapezius, EIH did not significantly differ between groups. No significant differences were found between the hEDS group and control group in the CPM response. The results demonstrate increased TSP in hEDS, suggesting increased central pain facilitation. EIH should be studied more extensively but may be disturbed when evaluated in the muscles that are activated during exercise. The CPM results are inconclusive and require more research. Studies regarding the mechanisms that underlie pain in hEDS are scarce, although it is the most prevalent and disabling symptom in this patient population. This study demonstrates increased temporal summation in hEDS and suggests that exercise-induced hypoalgesia may be reduced. Because exercise is a cornerstone in the multidisciplinary treatment of heritable connective tissue disorders, gaining knowledge in this field is important. Pressure stimuli were used to facilitate the international usability of the protocols, allowing for future data acquisition in large cohorts.

Conditioned Pain Modulation in Children: The Effects of Painful and Nonpainful Conditioning Stimuli

Conditioned pain modulation (CPM), a psychophysical measure in which 1 pain stimulus (conditioning stimulus) is used to inhibit another pain stimulus (test stimulus), is an important indicator of endogenous pain inhibition in adults, but is understudied in children. Preliminary evidence suggests that CPM effects are present in healthy children and are more robust in adolescents. However, developmental differences in younger children are not well documented and few studies control for potential distraction effects of the conditioning stimulus (CS). Participants were 54 healthy children aged 6 to 12 years. After a baseline pressure pain threshold (PPT) test, participants underwent 2 conditioning trials in which PPT was assessed while they placed their left hand in a water bath maintained at either 12 °C (painful CS) or 22 °C (nonpainful sham CS) in counterbalanced order. Results revealed a significant CPM effect. PPT values were significantly higher relative to baseline during the painful CS trial; PPT during the nonpainful CS trial did not differ from baseline. There were no significant age differences in magnitude of CPM effect. The results indicate that children as young as 6 years of age demonstrate CPM, suggesting that descending inhibitory pathways may be better developed in young children than previously thought. PerspectiveThis study was successful in producing inhibitory CPM effects in physically healthy children while controlling for sensory distraction. The findings provide strong evidence that the obtained CPM responses cannot be attributed to sensory distraction or other nonspecific effects. Future studies could utilize CPM paradigms to study various aspects of pediatric endogenous pain inhibition, in order to better predict pain responses and improve interventions.

Effects of neuroplasticity in people with knee osteoarthritis: A systematic review of the literature.

Background:Knee osteoarthritis (OA) is associated with chronic inflammation in somatic structures, which alters sensory afferents and leads to plastic changes in the nervous system.Methods:A systematic literature review was carried out, without language restrictions, period, or status of publication. The database used were Medline, EMBASE, Cochrane Library and clinicaltrials.gov. Extra bibliographic references were extracted through the discussion with specialists, and through scientific researches in conference papers.Results:The electronic search found 938 articles. When excluding duplicates and applying the inclusion/exclusion criteria, 5 studies were considered: 2 using EEG and 3 using TMS. Significant reduction of EEG activity in the cingulate medium cortex, reduction of conditioned pain modulation (CPM) in studies with EEG, as well as the occurrence of an association between pain and motor response threshold/intracortical pain facilitation in studies with TMS were observed.Conclusions:The study contributes to a better understanding of the neurophysiological changes seen in the cingulate medium cortex, decrease in CPM and motor response threshold/intracortical pain facilitation. Advances in neuroplasticity studies may aid in the screening for early diagnosis of knee OA in the future. However, more studies are necessary.

Exploring the relationship between meaningful conditioned pain modulation and stress system reactivity in healthy adults following exposure to the cold pressor task

BackgroundThe sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA) axis have been implicated in conditioned pain modulation (CPM). As there has recently been a push to identify meaningful CPM responses based on ± 2 SEM of the test stimulus, we sought to evaluate if meaningful CPM had relationships with both SNS and HPA axis reactivity. Methods50 university-aged healthy participants (25 males, 25 females) underwent evaluation of pressure pain detection threshold (PPDT), conditioned pain modulation (CPM), galvanic skin response (GSR) and salivary cortisol before and after a cold pressor test (CPT). Meaningful CPM was evaluated based on change ±2 SEM of baseline PPDT to classify participants as experiencing inhibition of pain, facilitation, or non-response. ResultsAs a group, there were no significant changes in PPDT or salivary cortisol after exposure to noxious cold. GSR was significantly elevated from baseline values during the CPT, and 10 min after (p < 0.001). When meaningful CPM was assessed, only 30% of participants experienced inhibitory CPM. Within this group, there was a large positive correlation ranging from r = 0.63 to 0.69 (p < 0.01) between CPM and the absolute change in GSR from baseline to immersion, and the immediate 5 min after immersion. ConclusionsThis work continues to support the growing body of literature suggesting that CPM is not universally experienced. Inhibitory CPM may be associated with an increase in SNS activity for healthy participants in reaction to noxious cold. Future work is required to ascertain individual characteristics (e.g., age, sex) that relate to CPM responses.

The association between pain-induced autonomic reactivity and descending pain control is mediated by the periaqueductal grey.

There is a strict interaction between the autonomic nervous system (ANS) and pain, which might involve descending pain modulatory mechanisms. The periaqueductal grey (PAG) is involved both in descending pain modulation and ANS, but its role in mediating this relationship has not yet been explored. Here, we sought to determine brain regions mediating ANS and descending pain control associations. Thirty participants underwent conditioned pain modulation (CPM) assessments, in which they rated painful pressure stimuli applied to their thumbnail, either alone or with a painful cold contralateral stimulation. Differences in pain ratings between 'pressure-only' and 'pressure+cold' stimuli provided a measure of descending pain control. In 18 of the 30 participants, structural scans and two functional MRI assessments, one pain-free and one during cold-pain were acquired. Heart rate variability (HRV) was simultaneously recorded. Normalised low-frequency HRV (LF-HRVnu) and the CPM score were negatively correlated; individuals with higher LF-HRVnu during pain reported reductions in pain during CPM. PAG-ventro-medial prefrontal cortex (vmPFC) and PAG-rostral ventromedial medulla (RVM) functional connectivity correlated negatively with the CPM. Importantly, PAG-vmPFC functional connectivity mediated the strength of the LF-HRVnu-CPM association. CPM response magnitude was also negatively correlated with vmPFC GM volume. Our multi-modal approach, using behavioural, physiological and MRI measures, provides important new evidence of interactions between ANS and descending pain mechanisms. ANS dysregulation and dysfunctional descending pain modulation are characteristics of chronic pain. We suggest that further investigation of body-brain interactions in chronic pain patients may catalyse the development of new treatments. KEY POINTS: Heart rate variability (HRV) is associated with descending pain modulation as measured by the conditioned pain modulation protocol (CPM). There is an association between CPM scores and the functional connectivity between the periaqueductal grey (PAG) and ventro-medial prefrontal cortex (vmPFC). CPM scores are also associated with vmPFC grey matter volume. The strength of functional connectivity between the PAG and vmPFC mediates the association between HRV and CPM. Our data provide new evidence of interactions between the autonomic nervous system and descending pain mechanisms.

Comparison of Thermal and Electrical Modalities in the Assessment of Temporal Summation of Pain and Conditioned Pain Modulation.

Temporal summation of pain (TSP) and conditioned pain modulation (CPM) can be measured using a thermode and a cold pressor test (CPT). Unfortunately, these tools are complex, expensive, and are ill-suited for routine clinical assessments. Building on the results from an exploratory study that attempted to use transcutaneous electrical nerve stimulation (TENS) to measure CPM and TSP, the present study assesses whether a “new” TENS protocol can be used instead of the thermode and CPT to measure CPM and TSP. The objective of this study was to compare the thermode/CPT protocol with the new TENS protocol, by (1) measuring the association between the TSP evoked by the two protocols; (2) measuring the association between the CPM evoked by the two protocols; and by (3) assessing whether the two protocols successfully trigger TSP and CPM in a similar number of participants. We assessed TSP and CPM in 50 healthy participants, using our new TENS protocol and a thermode/CPT protocol (repeated measures and randomized order). In the TENS protocol, both the test stimulus (TS) and the conditioning stimulus (CS) were delivered using TENS; in the thermode/CPT protocol, the TS was delivered using a thermode and the CS consisted of a CPT. There was no association between the response evoked by the two protocols, neither for TSP nor for CPM. The number of participants showing TSP [49 with TENS and 29 with thermode (p < 0.001)] and CPM [16 with TENS and 30 with thermode (p = 0.01)] was different in both protocols. Our results suggest that response to one modality does not predict response to the other; as such, TENS cannot be used instead of a thermode/CPT protocol to assess TSP and CPM without significantly affecting the results. Moreover, while at first glance it appears that TENS is more effective than the thermode/CPT protocol to induce TSP, but less so to induce CPM, these results should be interpreted carefully. Indeed, TSP and CPM response appear to be modality-dependent as opposed to an absolute phenomenon, and the two protocols may tap into entirely different mechanisms, especially in the case of TSP.

Changes in Pain Sensitivity and Conditioned Pain Modulation During Recovery From Whiplash-associated Disorders.

The objective of this study was to investigate the pain-sensory profile of patients with whiplash-associated disorders (WADs) prior and post 2 weeks of standardized rehabilitation and after a 6-month follow-up. Twenty-two WAD participants (grade II; 14 women) and 22 sex-matched and age-matched healthy pain-free controls were enrolled. Pressure pain thresholds (PPTs) were assessed at local and distal muscles. Conditioned pain modulation (CPM) of PPTs was assessed using cuff pressure around the upper arm. Referred area of pain following supra-threshold pressure stimulation of the infraspinatus muscle was recorded on a body chart. Psychometric variables (pain intensity, area of perceived pain, pain catastrophizing, kinesiophobia, sleep problems, and depression level) were assessed. WAD group additionally completed the Neck Disability Index. The WAD group demonstrated lower local PPTs compared with controls at all time points (P<0.05) and lower distal PPTs at baseline and at 2 weeks when compared with 6 months (within-group) (P<0.05). The WAD group had a reduced CPM response and larger induced referred pain areas compared with controls (P<0.05), while no within-group changes were observed at any time point. The WAD group reported higher pain intensity and perceived area of pain compared with controls at all time points (P<0.05) and a mean Neck Disability Index score of 41% at baseline, 16% at 2 weeks, and 4% at 6 months. Furthermore, the WAD group reported improvements in all other psychometric variables (P<0.05), although only pain catastrophizing levels were comparable to controls at 2 weeks. PPTs but not CPM improved in the WAD group and were comparable to controls following 2 weeks following standardized rehabilitation, indicating that normalization of CPM may not be required to recover from WAD.

Reduction in Pain Inhibitory Modulation and Cognitive-Behavioral Changes in Patients With Chronic Low Back Pain: A Case-Control Study

BackgroundRecent studies indicate that the assessment of conditioned pain modulation (CPM) responses and emotional factors can provide important information regarding chronification mechanisms, choices for more efficient therapeutic strategies, and clinical variables supporting a therapeutic prognosis. AimsTo investigate the impact of nonspecific chronic low back pain (NSCLBP) on CPM and psychosocial factors in individuals with NSCLBP compared with healthy controls. DesignCase-control study. MethodsEighteen patients with NSCLBP and 18 healthy controls were recruited for this study. Pain intensity and affective-emotional aspects of pain, functional disability, kinesiophobia, depression, anxiety, and catastrophizing pain were obtained using a questionnaire. A CPM protocol was established to assess the functioning of the descending inhibitory system, with a cold pressor test as a conditioning stimulus and pressure pain threshold as a test stimulus. The maximal isometric strength of the trunk extensors also was evaluated. ResultsHealthy participants demonstrated a greater CPM response than those with NSCLBP. Patients with NSCLBP exhibited significantly lower pressure pain threshold than healthy subjects. Moreover, patients with NSCLBP presented with a considerable exacerbation of cognitive-behavioral changes. NSCLBP patients showed diminished maximal isometric strength of the trunk extensor compared to healthy subjects. ConclusionsThe endogenous pain inhibition system is reduced in patients with NSCLBP, with significant cognitive-behavioral changes indicated by high levels of anxiety and moderate pain intensity. SettingClinical School of Physical Therapy of the Federal University of Delta of Parnaíba, Piauí - Brazil. Participants/Subjects36 subjects with and without NSCLBP.

A psychophysical study comparing massage to conditioned pain modulation: A single blind randomized controlled trial in healthy participants

IntroductionPain-inducing massage results in greater pain inhibition than pain free massage, suggesting a mechanism dependent on conditioned pain modulation (CPM). The purpose of this study was to test the hypothesis that pain inducing massage produces similar magnitude of reduction in pain sensitivity as a cold pressor task and that baseline conditioned pain modulation efficiency predicts pain inducing massage related hypoalgesia. MethodsSixty healthy participants were randomly assigned to receive either pain inducing massage to the neck, cold pressor task to the hand, or pain free massage to the neck. Participants also underwent pre and immediate post-intervention quantitative sensory testing. A repeated measures ANCOVA determined between group differences in pain sensitivity changes. ResultsPain inducing massage used as a conditioning stimulus resulted in comparable experimental pain sensitivity changes as a cold pressor task (p > 0.05). Pain intensity during the intervention demonstrated a weak correlation (r = 0.20, p = 0.12) with changes in pain sensitivity at a remote site. Individuals with an efficient CPM at baseline who received the pain inducing massage displayed greater increases in pressure pain threshold compared to individuals with a less efficient CPM indicating the potential benefit of treatment stratification by mechanism. ConclusionAlthough pain inducing massage resulted in less self-reported pain than a cold pressor task, both resulted in similar magnitude of the CPM response, suggesting shared underlying mechanisms. Understanding mechanisms of interventions can move us closer to mechanistic based treatments for pain which is consistent with a personalized medicine approach to care.