Lower Heat Pain Thresholds Research Articles

Phantom limb pain after unilateral arm amputation is associated with decreased heat pain thresholds in the face

AbstractBackgroundThe mechanisms underlying chronic phantom limb pain (PLP) are complex and insufficiently understood. Altered sensory thresholds are often associated with chronic pain but quantitative sensory testing (QST) in PLP has so far been inconclusive due to large methodological variation between studies and small sample sizes.MethodsIn this study, we applied QST in 37 unilateral upper‐limb amputees (23 with and 14 without PLP) and 19 healthy controls. We assessed heat pain (HPT), pressure pain, warmth detection and two‐point discrimination thresholds at the residual limb, a homologous point and the thenar of the intact limb as well as both corners of the mouth.ResultsWe did not find significant differences in any of the thresholds between the groups. However, PLP intensity was negatively associated with HPT at all measured body sites except for the residual limb, indicating lower pain thresholds with higher PLP levels. Correlations between HPT and PLP were strongest in the contralateral face (r = −0.65, p < 0.001). Facial HPT were specifically associated with PLP, independent of residual limb pain (RLP) and various other covariates. HPT at the residual limb, however, were significantly associated with RLP, but not with PLP.ConclusionWe conclude that the association between PLP and, especially facial, HPT could be related to central mechanisms.SignificancePhantom limb pain (PLP) is still poorly understood. We show that PLP intensity is associated with lower heat pain thresholds, especially in the face. This finding could be related to central nervous changes in PLP.

During capsaicin-induced central sensitization, brush allodynia is associated with baseline warmth sensitivity, whereas mechanical hyperalgesia is associated with painful mechanical sensibility, anxiety and somatization.

Mechanical hyperalgesia and allodynia incidence varies considerably amongst neuropathic pain patients. This study explored whether sensory or psychological factors associate with mechanical hyperalgesia and brush allodynia in a human experimental model. Sixty-six healthy volunteers (29 male) completed psychological questionnaires and participated in two quantitative sensory testing (QST) sessions. Warmth detection threshold (WDT), heat pain threshold (HPT) and suprathreshold mechanical pain (STMP) ratings were measured before exposure to a capsaicin-heat pain model (C-HP). After C-HP exposure, brush allodynia and STMP were measured in one session, whilst mechanical hyperalgesia was measured in another session. WDT and HPT measured in sessions separated by 1month demonstrated significant but moderate levels of reliability (WDT: ICC=0.5, 95%CI [0.28, 0.77]; HPT: ICC=0.62, 95%CI [0.40, 0.77]). Brush allodynia associated with lower WDT (z=-3.06, p=0.002; ϕ=0.27). Those with allodynia showed greater hyperalgesia intensity (F=7.044, p=0.010, ηp 2 =0.107) and area (F=9.319, p=0.004, ηp 2 =0.163) than those without allodynia. No psychological self-report measures were significantly different between allodynic and nonallodynic groups. Intensity of hyperalgesia in response to lighter mechanical stimuli was associated with lower HPT, higher STMP ratings and higher Pain Sensitivity Questionnaire scores at baseline. Hyperalgesia to heavier probe stimuli associated with state anxiety and to a lesser extent somatic awareness. Hyperalgesic area associated with lower baseline HPT and higher STMP ratings. Hyperalgesic area was not correlated with allodynic area across individuals. These findings support research in neuropathic pain patients and human experimental models that peripheral sensory input and individual sensibility are related to development of mechanical allodynia and hyperalgesia during central sensitization, whilst psychological factors play a lesser role. We evaluated differential relationships of psychological and perceptual sensitivity to the development of capsaicin-induced mechanical allodynia and hyperalgesia. Fifty percent of healthy volunteers failed to develop mechanical allodynia. Baseline pain sensitivity was greater in those developing allodynia and was related to the magnitude and area of hyperalgesia. State psychological factors, whilst unrelated to allodynia, were related to mechanical hyperalgesia. This supports that the intensity of peripheral sensory input and individual sensibility are related to development of mechanical allodynia and hyperalgesia during central sensitization, whilst psychological factors play a lesser role.

Central pain modulatory mechanisms of attentional analgesia are preserved in fibromyalgia.

Fibromyalgia is a prevalent pain condition that is associated with cognitive impairments including in attention, memory, and executive processing. It has been proposed that fibromyalgia may be caused by altered central pain processing characterised by a loss of endogenous pain modulation. We tested whether attentional analgesia, where cognitive engagement diminishes pain percept, was attenuated in patients with fibromyalgia (n = 20) compared with matched healthy controls (n = 20). An individually calibrated, attentional analgesia paradigm with a 2 × 2 factorial design was used with brain and brainstem-focussed functional magnetic resonance imaging. Patients with fibromyalgia had both lower heat pain thresholds and speeds in a visual attention task. When this was taken into account for both attentional task and thermal stimulation, both groups exhibited an equivalent degree of attentional analgesia. Functional magnetic resonance imaging analysis showed similar patterns of activation in the main effects of pain and attention in the brain and brainstem (with the sole exceptions of increased activation in the control group in the frontopolar cortex and the ipsilateral locus coeruleus). The attentional analgesic effect correlated with activity in the periaqueductal gray and rostral ventromedial medulla. These findings indicate that patients with fibromyalgia can engage the descending pain modulatory system if the attentional task and noxious stimulus intensity are appropriately titrated.

Quantitative sensory testing to evaluate and compare the results after epidural injection and simple discectomy, in patients with radiculopathy secondary to lumbar disc herniation

The objective assessment of the radiculopathy secondary to lumbar disc herniation is essential to optimize treatment. The quantitative sensory test (QST) is a useful tool to evaluate somatosensory nerves. The aim of our study is quantifying by QST the alterations of patients treated by epidural injections (EI) or surgical lumbar decompression (LD). A prospective, cohort study has done in Hospital Universitario Rio Hortega, Valladolid, Spain, between January 2014 and December 2016.The study includes 74 patients (40 men) who underwent EI (50) or LD (24) with lumbar disc herniation and treated by EI or LD. Participants underwent a brief battery of QST at baseline and after 1, 3 and 6months of follow-up. QST threshold were measured in three series of five warm and cold stimuli (cold detection threshold, warm detection threshold, cold pain threshold, heat pain threshold) bilateral. Additionally, pain assessment (Visual Analogue Scale) and neurological examination was performed. Thermal thresholds were analysed and compared. In the EI group, warm detection threshold (WDT) measurements were significantly lower after 3 and 6months of follow-up (40.44 ± 3.42°C vs. 38.30 ± 3.73°C and 37.48 ± 4.58°C respectively, p = 0.031 and p = 0.043). LD group showed lower WDT measurements at 1, 3 and 6months of follow up (40.20 ± 2.97°C vs., 37.98 ± 2.04°C, 37.43 ± 3.80°C and 36.55 ± 2.77°C respectively, p = 0.049, p = 0.032 and p = 0.024) and lower heat pain threshold (HPT) levels after 3 and 6months of follow-up (48.75 ± 1.37°C vs. 43.26 ± 0.60°C and 42.06 ± 1.37°C respectively, p = 0.037 and p = 0.021). QST explorations were compared between both groups. At 1-month follow-up only the WDT parameter was different, higher in EI group (40.98 ± 4.04°C vs. 37.98 ± 2.04°C, p = 0.043). There were no differences in any parameter measured by QST after 3 and 6-months follow-up between both groups. Epidural injection should be considered the first-step of treatment.

Structural alterations of the brainstem in migraine.

Atypical brainstem modulation of pain might contribute to changes in sensory processing typical of migraine. The study objective was to investigate whether migraine is associated with brainstem structural alterations that correlate with this altered pain processing.MRI T1-weighted images of 55 migraine patients and 58 healthy controls were used to: (1) create deformable mesh models of the brainstem that allow for shape analyses; (2) calculate volumes of the midbrain, pons, medulla and the superior cerebellar peduncles; (3) interrogate correlations between regional brainstem volumes, cutaneous heat pain thresholds, and allodynia symptoms.Migraineurs had smaller midbrain volumes (healthy controls = 61.28 mm3, SD = 5.89; migraineurs = 58.80 mm3, SD = 6.64; p = 0.038), and significant (p < 0.05) inward deformations in the ventral midbrain and pons, and outward deformations in the lateral medulla and dorsolateral pons relative to healthy controls. Migraineurs had a negative correlation between ASC-12 allodynia symptom severity with midbrain volume (r = − 0.32; p = 0.019) and a positive correlation between cutaneous heat pain thresholds with medulla (r = 0.337; p = 0.012) and cerebellar peduncle volumes (r = 0.435; p = 0.001).Migraineurs with greater symptoms of allodynia have smaller midbrain volumes and migraineurs with lower heat pain thresholds have smaller medulla and cerebellar peduncles. The brainstem likely plays a role in altered sensory processing in migraine and brainstem structure might reflect severity of allodynia and hypersensitivity to pain in migraine.

Pain Catastrophizing and Anxiety are Associated With Heat Pain Perception in a Community Sample of Adults With Chronic Pain.

The principle aim of this study was to investigate the associations between heat pain (HP) perception, pain catastrophizing, and pain-related anxiety in a heterogenous cohort of community-dwelling adults with chronic pain admitted to a 3-week outpatient pain rehabilitation program. All adults consecutively admitted to an outpatient pain rehabilitation program from July 2009 through January 2011 were eligible for study recruitment (n=574). Upon admission, patients completed the Pain Catastrophizing Scale (PCS), the short version of the Pain Anxiety Symptoms Scale (PASS-20), and HP perception was assessed using a standardized quantitative sensory testing (QST) method of levels. Greater PCS scores were significantly correlated with lower standardized values of HP threshold (HP 0.5) (P=0.006) and tolerance (HP 5) (P=0.003). In a multiple variable model adjusted for demographic and clinical factors known to influence HP perception, every 10-point increase in the PCS was associated with a -0.124 point change in HP 0.5 (P=0.014) and a -0.142 change in HP 5 (P=0.014) indicating that participants with higher PCS scores had lower HP thresholds and tolerances, respectively. Similarly, greater PASS-20 scores significantly correlated with lower standardized values of HP 0.5 and HP 5. In a multiple variable model, every 10-point increase in the PASS-20 was associated with a -0.084 point change in HP 0.5 (P=0.005) and a -0.116 point change in HP 5 (P=0.001) indicating that participants with higher PASS-20 scores had lower HP thresholds and tolerances, respectively. The findings of this study extend the use of a standardized method for assessing HP in a heterogenous sample of adults with chronic pain. Although pain catastrophizing shares significant variance with pain-related anxiety, our findings suggest that either measure would be appropriate for use in future studies that incorporate the QST method of levels.

Pain modulatory phenotypes differentiate subgroups with different clinical and experimental pain sensitivity.

Pain biomarkers are warranted for individualized pain management. Based on different pain modulatory phenotypes, the objectives of this study were to explore the existence of subgroups within patients with nonmalignant chronic pain and to investigate differences in clinical pain and pain hypersensitivity between subgroups. Cuff algometry was performed on lower legs in 400 patients with chronic pain to assess pressure pain threshold, pressure pain tolerance, temporal summation of pain (TSP: increase in pain scores to 10 repeated stimulations), and conditioned pain modulation (CPM: increase in cuff pressure pain threshold during cuff pain conditioning on the contralateral leg). Heat detection and heat pain thresholds at clinical painful and nonpainful body areas were assessed. Based on TSP and CPM, 4 distinct groups were formed: group 1 (n = 85) had impaired CPM and facilitated TSP; group 2 (n = 148) had impaired CPM and normal TSP; group 3 (n = 45) had normal CPM and facilitated TSP; and group 4 (n = 122) had normal CPM and normal TSP. Group 1 showed more pain regions than the other 3 groups (P < 0.001), indicating that impaired CPM and facilitated TSP play an important role in widespread pain. Groups 1 and 2 compared with group 4 had lower heat pain threshold at nonpainful areas and lower cuff pressure pain tolerance (P < 0.02), indicating that CPM plays a role for widespread hyperalgesia. Moreover, group 1 demonstrated higher clinical pain scores than group 4 (P < 0.05). Although not different between subgroups, patients were profiled on demographics, disability, pain catastrophizing, and fear of movement. Future research should investigate interventions tailored towards these subgroups.

Structural Brain Alterations in Community Dwelling Individuals with Chronic Joint Pain.

Central sensitization in chronic pain involves structural brain changes that influence vulnerability to pain. Identifying brain regions involved in pain processing and sensitization can provide more insight into chronic pain. This study examines structural brain changes in chronic pain and experimental pain in a large population-based study. For 3892 participants in the Rotterdam study, global and regional MR imaging brain volumes were automatically segmented and quantified. Chronic joint pain was defined as pain for more than half of all days during the past 6 weeks. Heat pain thresholds were measured in a subset of 1538 individuals. The association between the presence of chronic joint pain and global and lobar brain volumes was studied. Subsequently, literature was reviewed and the association of chronic pain and heat pain thresholds with 11 brain regions associated with musculoskeletal pain in previous publications was studied. Total gray matter volume was smaller in women with chronic pain (β = -0.066, P = .016). This effect was primarily driven by lower gray matter volume in the temporal lobe (β = 0.086, P = .005), the frontal lobe (β = -0.060, P = .039), and the hippocampus (β = -0.099, P = .002). In addition, we observed that a lower heat pain threshold was associated with smaller volumes of the hippocampus (β = 0.017, P = .048), the thalamus (β = 0.018, P = .009), and the anterior cingulate cortex (β = -0.016, P = .037). In men, no significant associations were observed. The primary identified brain areas, the temporal and frontal lobes and the hippocampus, indicated involvement of emotional processing. The volumetric differences found indicated a sex-specific neuroplasticity in chronic pain. These results emphasized sex-specific and multidisciplinary pain treatment.

Hypersensitivity to pain in congenital blindness

Vision is important for avoiding encounters with objects in the environment that may imperil physical integrity. We tested whether, in the absence of vision, a lower pain threshold would arise from an adaptive shift to other sensory channels. We therefore measured heat and cold pain thresholds and responses to suprathreshold heat stimuli in 2 groups of congenitally blind and matched normal-sighted participants. We also assessed detection thresholds for innocuous warmth and cold, and participants’ attitude toward painful encounters in daily life. Our results show that, compared to sighted subjects, congenitally blind subjects have lower heat pain thresholds, rate suprathreshold heat pain stimuli as more painful, and have increased sensitivity for cold pain stimuli. Thresholds for nonpainful thermal stimulation did not differ between groups. The results of the pain questionnaires further indicated that blind subjects are more attentive to signals of external threats. These findings indicate that the absence of vision from birth induces a hypersensitivity to painful stimuli, lending new support to a model of sensory integration of vision and pain processing.

Sexual and Relationship Satisfaction and Vestibular Pain Sensitivity Among Women with Provoked Vestibulodynia

Provoked vestibulodynia (PVD) is a common cause of painful intercourse. Despite the fact that PVD is associated with high levels of pain and negative impact on women's sexuality, research has not examined associations between affected women's pain sensitivity and their sexual and relationship satisfaction. This study aimed to examine sexual and relationship functioning/satisfaction and vestibular pain sensitivity among PVD-affected women, and potential associations between these variables. Participants were 17 women with PVD and 17 matched controls. Women were assessed via a gynecological examination, structured interview, and the Female Sexual Function Index (FSFI), Golombok Rust Inventory of Sexual Satisfaction (GRISS), and Dyadic Adjustment Scale (DAS). Additionally, women completed a quantitative sensory testing session to assess vestibular pain thresholds and associated pain ratings; specifically, vestibular pressure-pain and heat pain thresholds were measured. Gynecological and intercourse pain ratings; FSFI; GRISS; DAS; vestibular pressure-pain threshold; and vestibular heat pain thresholds. PVD-affected women reported significantly decreased sexual function in comparison with controls. While no differences in relationship satisfaction were found between groups, women with PVD did report less sexual satisfaction on the FSFI. PVD-affected women also reported significantly higher vestibular pain ratings associated with the gynecological examination and heat pain tolerance procedures, and lower pressure-pain threshold, heat pain threshold, and heat pain tolerance at the vestibule in comparison with controls. Among women with PVD, lower heat pain threshold was associated with less sexual satisfaction, and higher pain ratings related to intercourse and heat pain tolerance, respectively, were associated with lower sexual function and satisfaction. The results indicate that women with PVD experience negative sexual effects and increased pain sensitivity. This study also suggests that some aspects of pain may be related to lower levels of sexual function and satisfaction among affected women.

Increased pain sensitivity among adults reporting irritable bowel syndrome symptoms in a large population-based study

The aim of this study was to examine whether irritable bowel syndrome (IBS) is associated with increased somatic pain sensitivity in a large population-based sample and to test whether this association was independent of sex, age, comorbid chronic pain, and psychological distress. Pain sensitivity tests included assessment of heat-pain threshold (N=4054) and pressure-pain threshold (N=4689) and of cold-pressor pain intensity and tolerance (N=10,487). Cox regression and analysis of variance (ANOVA) were used to assess the relationship between IBS and pain sensitivity in stepwise multivariate models. The prevalence of IBS symptoms meeting the ROME II criteria was 5.3%. Compared with control subjects, IBS cases had reduced cold-pressor tolerance (hazard ratio=1.4, P<.01), increased cold-pressor pain intensity ratings (z-score=+0.20, P<0.01), and lower heat-pain thresholds (z-score=–0.20, P<0.01), after adjusting for sex and age. These results were only slightly attenuated and remained significant when controlling for comorbid chronic pain and psychological distress. Results for pressure-pain threshold were not significant. Heat- and cold-pressor pain sensitivity was greatest for the IBS reporting severe chronic abdominal pain, indicating that hyperalgesia in IBS is related to degree of clinical pain rather than to the diagnosis per se. Because all pain tests were all carried out on the upper extremities, our findings indicate the presence of widespread hyperalgesia in IBS, which may be a contributing factor to the high rate of comorbid pain seen in this patient group.

A Preliminary Study on the Effects of Self-Reported Dietary Caffeine on Pain Experience and Postoperative Analgesia.

Caffeine reduces the amount of analgesic medications necessary to provide postoperative pain (POP) relief and augments treatments for headaches and dental pain. Despite considerable evidence of its beneficial effects, little is understood about the role of dietary caffeine consumption on baseline pain sensitivity or POP following oral surgery. Baseline experimental pain testing (quantitative sensory testing [QST]) using four stimulus modalities was conducted on 30 healthy adults (53% females) before surgical extraction of four third molars. Self-reported caffeine ingestion was reported before QST, and on the day of surgery, preoperative and postoperative caffeine plasma concentrations (CPC) were measured by mass spectrometry. POP ratings were obtained at timed intervals. In QST, compared to subjects who self-reported no caffeine intake, those who self-reported caffeine ingestion demonstrated a higher pain sensitivity, particularly, on ramp and hold sustained heat at 44°C and 46°C, as well as a lower heat pain threshold and tolerance (p=0.05). Differences approached significance (p=0.06) in POP between subjects with CPC above 300 ng/mL and those with CPC below 300 ng/mL. Specifically, those with >300 ng/mL CPC had a slightly lower POP (mean 2.43, range 0-5) compared to those with <300 ng/mL CPC whose POP ratings were slightly higher (mean 2.89) with a greater variability (range 0-9.5). Self-reported, dietary caffeine intake was associated with higher QST ratings with lower threshold and tolerance particularly on heat pain modalities. External factors (i.e., analgesic dosage) may have played a role in the analgesic effects of caffeine on POP in oral surgery, especially in individuals with CPC exceeding 300 ng/mL who reported lower pain.

Patients with Sickle Cell Disease Have Increased Sensitivity to Cold and Heat Stimuli, 2

Abstract 2116Sickle Cell Disease (SCD) pain is associated with colder temperatures, touch, and increased wind speed and barometric pressure. The specific array of associated factors suggests hypersensitivity to tactile stimuli, a characteristic of neuropathic pain. Sickle mice exhibit hypersensitivity at baseline compared to controls to cold, heat, and mechanical stimuli via a TRPV1 mediated pathway. However, it is not known whether humans experience this same hypersensitivity. Thus, the objective of this study was to quantify sensitivity differences to thermal (heat, cold) and mechanical stimuli between SCD patients and healthy African American controls. We hypothesized SCD patients will exhibit hypersensitivity to thermal and mechanical stimuli compared to controls and this hypersensitivity will worsen with age and frequency of pain.We conducted a cross-sectional study of SCD patients in baseline health and race-matched controls age ≥ 7 yrs. Our primary outcome was detection of hypersensitivity to thermal and mechanical stimuli. We excluded those with a pain phenotype other than SCD, overt stroke, analgesics within 24 hrs of testing, or acute SCD pain event within 2 weeks of testing. Subjects underwent quantitative sensory testing (QST) to thermal and mechanical stimuli. QST evaluates the somatosensory system detecting sensory loss (hyposensitivity) or gain (hypersensitivity). Thermal stimulation was performed with a Thermal Sensory Analyzer (Medoc;Israel), an FDA approved computer-assisted device that delivers cold and warm stimuli via a thermode attached to the skin (baseline temperature, 32°C; stimulus range, 0–50°C). Mechanical testing was performed using graded vonFrey monofilaments (force range 0.255 mN to 1078.731 mN). Testing was done on the thenar eminence of the non-dominant hand. Primary outcomes included: 1) Cold Pain Threshold (°C), 2) Heat Pain Threshold (°C), 3) Mechanical Pain Threshold (mN) as reported by “method of limits” where subjects pushed a button (thermal) or spoke (mechanical) when the progressive stimulus was painful. The final outcome was the computed mean of 3 tests (thermal) and 5 tests (mechanical).Independent samples t-tests were used to compare outcomes between SCD patients and controls. Linear regression was used to evaluate the impact of age and gender on pain thresholds in both groups and the impact of lifetime history of pain, defined as total number of emergency department visits or hospitalizations for pain, on pain thresholds in SCD patients.55 SCD patients and 57 controls were recruited (Jan 2010-June 2011). There were no differences in mean age (15.4 yrs vs.16.3 yrs; p=0.59, t-test) or gender (SCD=60% female vs. Controls=56% female; p=0.70, Pearson Chi-Square). SCD genotypes were 67% (n=37) HbSS, 18% (n=10) HbSC, 11% (n=6), HbSβ+thal, and 4% (n=2) other. SCD patients had significantly lower cold pain thresholds (p=0.008) and heat pain thresholds (p=0.04) compared to controls (Table 1). There were no differences in mechanical pain thresholds (p=0.38) (Table 1). Older age was associated with lower cold pain thresholds (parameter estimate=0.19°C; p=0.05), lower heat pain thresholds (parameter estimate=0.13°C; p=0.0069), and lower mechanical pain thresholds (parameter estimate=0.11mN; p=0.02) in both groups. Gender had no effect on the outcomes (cold pain threshold, p=0.15; heat pain threshold, p=0.07; mechanical pain threshold, p=0.29). Total number of lifetime SCD pain events had no effect on the outcomes (cold pain threshold, p=0.91; heat pain threshold, p=0.65, mechanical pain threshold, p=0.77).SCD patients in baseline health experience increased sensitivity to cold and heat stimuli compared to race-matched controls and this sensitivity worsens with older age. These findings suggest peripheral sensitization may exist in SCD. Further research into how cold and heat sensing receptors and pathways contribute to SCD pain is warranted. Ultimately, this may lead to the development of novel therapeutics targeted to the specific underlying neurobiology of SCD pain that aids in the treatment or prevention of SCD pain.Table 1Pain Thresholds of SCD Patients and Healthy Controls.OutcomeSCD Patients (Mean ± SD)Controls (Mean ± SD)P-valueCold Pain Threshold (°C)18.5 (7.7)14.1 (9.4)0.008Heat Pain Threshold (°C)42.5 (4.4)44.3 (4.6)0.04Mechanical Pain Threshold (mN)303.9 (409.6)375.6 (451.2)0.38 Disclosures:No relevant conflicts of interest to declare.

Analysis of thermal pain sensitivity and psychological profiles in different subgroups of TMD patients

This study evaluated differences in pain sensitivities and psychological profiles among different temporomandibular disorder (TMD) pain subtypes. Evaluation was done on 36 normal subjects and 39 TMD patients with high Graded Chronic Pain scale scores. TMD patients were placed in three pain subgroups (myogenous, arthrogenous, mixed) using the Research Diagnostic Criteria for TMD (RDC/TMD) axis I guidelines. RDC/TMD axis II profiles including depression and somatization were analysed. Cold pain threshold (CPT), heat pain threshold (HPT), and heat pain tolerance threshold (HPTT) were measured on three facial regions (anterior temporalis, masseter, TMJ) and a leg region (anterior tibialis). The arthrogenous pain subgroup showed significantly higher CPT and lower HPT and HPTT in the facial region, and lower HPTT in the anterior tibialis region compared with normal and myogenous pain subgroups. The myogenous pain subgroup had significantly higher somatization scores than normal and arthrogenous pain subgroups, and higher depression scores than normal subjects. The results suggest that peripheral and/or central sensitization are present in chronic arthrogenous pain more so than in myogenous pain, and this phenomenon appears to take place regardless of the patient's psychological profiles. These results may explain the underlying mechanism that aggravates TMD pain.