Painful cold-heat segmental pulse stimulation provokes the thermal pain illusion.

PURPOSE/AIM: The thermal grill illusion is a paradoxical pain sensation induced by simultaneous exposure to spatially separated, non-painful, cold, and warm stimuli. This study aimed to determine whether paradoxical sensations are also evoked by simultaneous exposure to painful cold-heat stimuli and whether the mechanism involves modulation by segmental and extra-segmental spatial integration. MATERIALS AND METHODS: Sensory perceptions were triggered by simultaneous application of painful cold-heat pulse stimuli using a developed bedside tool equipped with quantitative thermal stimulator devices. Four conditions were investigated: (1) one device placed on the forearm (condition 1, control); (2) two devices placed on the forearm (condition 2, ipsilateral segmental integration); (3) two devices placed on the forearm and ipsilateral thigh (condition 3, extra-segmental integration); and (4) two devices placed bilaterally on the forearms (condition 4, contralateral segmental integration). The evoked perceptions of paradoxical heat sensation and the loss of cold or heat sensation were evaluated. RESULTS: The aforementioned phenomena were experienced by 11(35.4%), 3(9.7%), 3(9.7%), and 0(0.0%) subjects for conditions 1-4, respectively. Fisher's exact test revealed significant differences (p=.001) among the four conditions. However, Bonferroni post hoc analysis revealed significant differences only between conditions 1 and 4 (p=.005). CONCLUSIONS: Simultaneous painful cold-heat pulse stimulation can induce paradoxical sensations similar to those shown for non-painful thermal (cold and heat) stimuli. They were predominantly evoked by ipsilateral integration. Paradoxical sensations have diagnostic value, and quantifying them using a simple bedside tool may be useful in the clinical setting.

Photobiomodulation enhanced endogenous pain modulation in healthy volunteers.

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

Effects of exercise therapy on painful temporomandibular disorders.

Temporomandibular disorders (TMD) are common chronic musculoskeletal pain conditions among orofacial pain. Painful TMD condition such as myalgia and arthralgia can be managed by exercise therapy. However, as it is hard to access actual effect of each modality that is included in an exercise therapy programme due to multiple choice of the management modality, their efficacy remains controversial. Therefore, this review focused on the effects of exercise therapy for the management of painful TMD. The aims of this review were to summarise the effects of exercise therapy for major symptoms of painful TMD and to establish a guideline for the management of painful TMD, resulting in higher quality and reliability of dental treatment. In this review, exercise modalities are clearly defined as follows: mobilisation exercise, muscle strengthening exercise (resistance training), coordination exercise and postural exercise. Furthermore, pain intensity and range of movements were focused as outcome parameters in this review. Mobilisation exercise including manual therapy, passive jaw mobilisation with oral appliances and voluntary jaw exercise appeared to be a promising option for painful TMD conditions such as myalgia and arthralgia. This review addressed not only the effects of exercise therapy on various clinical conditions of painful TMD shown in the past, but also an urgent need for consensus among dentists and clinicians in terms of the management of each condition, as well as terminology.

Conditioned pain modulation in temporomandibular disorders (TMD) pain patients.

The aims were to investigate (1) if temporomandibular disorders (TMD) patients with temporomandibular joint (TMJ) pain had different conditioned pain modulation (CPM) compared with healthy subjects and, (2) if clinical pain characteristics influenced CPM. Sixteen TMD pain patients and 16 age-matched healthy subjects were participated. A mechanical conditioning stimulus (CS) was applied to pericranial muscles provoking a pain intensity of 5/10 on a visual analogue scale. Pressure pain thresholds (PPT) and pressure pain tolerance thresholds (PPTol) were assessed at masseter, forearm and painful TMJ (only PPT) before, during, and 20 min after CS. Data were analyzed with ANOVAs. The correlations between CPM effect and ratings of TMD pain intensity on a numerical rating scale (NRS) or the pain duration were calculated (correlation coefficient; R). The relative PPT and PPTol increases (mean for the three assessment sites) during CS were significantly higher than baseline in healthy subjects (43.0 ± 3.6, 33.0 ± 4.0 %; P < 0.001, P < 0.001) but not in the TMD pain patients (4.9 ± 2.7, -1.4 ± 4.1 %; P = 0.492, P = 1.000) with significant differences between groups (P < 0.001). In the patients, the relative PPT changes during CS were not significantly higher than baseline at TMJ (5.3 ± 3.8 %, P = 0.981) and masseter (-2.8 ± 4.8 %, P = 1.000) but significantly higher at forearm (12.3 ± 4.7 %, P = 0.039). No correlation was detected between TMD pain intensity and CPM effect (R = -0.261; P = 0.337) or between pain duration and CPM effect (R = -0.423; P = 0.103) at painful TMJ. These findings indicate that CPM is impaired in TMD pain patients especially at sites with chronic pain but not at pain-free sites and that the clinical pain characteristics do not influence CPM.

SARS-CoV-2 detection in pediatric dental clinic wastewater reflects the number of local COVID-19 cases in children under 10 years old.

This was the first longitudinal study to analyze dental clinic wastewater to estimate asymptomatic SARS-CoV-2 infection trends in children. We monitored wastewater over a 14-month period, spanning three major COVID-19 waves driven by the Alpha, Delta, and Omicron variants. Each Saturday, wastewater was sampled at the Pediatric Dental Clinic of the only dental hospital in Japan's Saitama Prefecture. The relationship between the weekly number of cases in Saitama Prefecture among residents aged < 10 years (exposure) and wastewater SARS-CoV-2 RNA detection (outcome) was examined. The number of cases was significantly associated with wastewater SARS-CoV-2 RNA positivity (risk ratio, 5.36; 95% confidence interval, 1.72-16.67; Fisher's exact test, p = 0.0005). A sample from Week 8 of 2022 harbored the Omicron variant. Compared to sporadic individual testing, this approach allows continuous population-level surveillance, which is less affected by healthcare seeking and test availability. Since wastewater from pediatric dental clinics originates from the oral cavities of asymptomatic children, such testing can provide important information regarding asymptomatic COVID-19 in children, complementing clinical pediatric data.

Perioperative Nerve Blockade Reduces Acute Postoperative Pain after Orthognathic Surgery.

Background: The role of perioperative pain management is not only to reduce acute postoperative pain (POP) but also to prevent chronic POP. It would be important to know the usefulness of nerve blockade for perioperative management. However, it has not been extensively studied in orofacial surgery. The objective of the study was to investigate whether perioperative nerve blockade reduces acute POP after orthognathic surgery. Methods: Patients scheduled for orthognathic surgery were retrospectively reviewed ("preblock group": the nerve blockade was performed before emergence from general anesthesia, and "no preblock group": the nerve blockade was not performed before emergence from general anesthesia). The visual analog scale (VAS; 0-100 mm)-POP intensity, the VAS-POP areas under the curves (VASAUCs (mm × day)) in addition to VASAUCs for postoperative hours 6 (VASAUC_6), 12 (VASAUC_12), 18 (VASAUC_18), and 24 (VASAUC_24), the analgesic requirement period (day), and the number of days with pain (day) were analyzed. Data are presented as median (interquartile range) values. Results: Fifty-six patients (preblock group, 22; no preblock group, 34) were included (21 males, 35 females; age: 22.0 [21.0-28.0] years). VASAUC_6, VASAUC_12, VASAUC_18, and VASAUC_24 in the preblock group were significantly smaller than those in the no preblock group (3.5 [2.0-7.2] vs. 7.4 [5.1-10.0], p = 0.0007; 9.5 [6.4-13.7] vs. 15.0 [7.2-22.9], p = 0.042; 15.7 [10.3-23.1] vs. 29.3 [18.9-37.2], p = 0.0002; and 17.6 [12.7-27.2] vs. 39.5 [22.9-46.9], p = 0.001, respectively). There were no significant differences between the 2 groups in VASAUC, the analgesic requirement period, and the number of days with pain (p > 0.05). Conclusions: Perioperative nerve blockade reduces POP after orthognathic surgery, especially for the acute postoperative period.

Conditioned pain modulation is not associated with thermal pain illusion.

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

Preoperatively assessed offset analgesia predicts acute postoperative pain following orthognathic surgery.

OBJECTIVES: High intensity and longer duration of acute postoperative pain are generally associated with a higher risk of developing chronic postoperative pain. Therefore, it is important to identify the preoperative predictors for acute postoperative pain. Preoperative evaluation of offset analgesia (OA) and the Pain Catastrophising Scale (PCS) may be potential predictors for acute postoperative pain. This study aimed to investigate the relationship between preoperative OA, PCS, and acute postoperative pain following orthognathic surgery. METHODS: Thirty patients (19 females) scheduled to undergo orthognathic surgery were included in this study. OA and PCS were evaluated preoperatively, and the patients reported their postoperative pain intensity using the visual analogue scale [0-100 mm] until it reached zero (number of days with pain). OA was induced on the dominant forearm via three consecutive painful heat pulses delivered for 5 s (T1=46 °C), 5 s (T2=47 °C), and 20 s (T3=46 °C). Subsequently, the associations between OA, PCS, and the number of days with pain were analysed. RESULTS: The median duration of postoperative pain was 10.3 days. Multiple linear regression analysis showed a significant (p=0.0019) predictive value of OA (p=0.008) for the number of days with pain. The PCS-magnification component was positively correlated with the number of days with pain (R=0.369, p=0.045), with no predictive values of PCS-total and PCS-subscale scores observed. CONCLUSIONS: Preoperative evaluation of OA may be a new individualised, predictive tool for the number of days with acute postoperative pain following orthognathic surgery; hence, a possible biomarker for the patient's vulnerability to developing chronic postoperative pain. ETHICAL COMMITTEE NUMBER: The study was approved by the Ethics Committee of Meikai University (A1624, A2113). TRIAL REGISTRY NUMBER: This study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) Clinical Trial (Unique ID: UMIN000026719, UMIN000046957).

Conditioned pain modulation evoked by a mechanical craniofacial stimulus is not influenced by noxious stimulation of the temporomandibular joint.

AIMS: To investigate the influence of noxious stimulation of the temporomandibular joint (TMJ) on conditioned pain modulation (CPM) and the possible influence of gender on such CPM effects in the craniofacial region of humans. METHODS: Twenty healthy men and 20 healthy women participated in two sessions. Conditioning stimulation (CS) was standardized mechanical stimulation of pericranial muscles at a pain level of 5 on a 0 to 10 visual analog scale (VAS). Intra-articular electrical stimuli were applied to the left TMJ with an intensity around VAS = 5 (painful session). No electrical stimulation was applied in the control session. Pressure pain threshold (PPT) and pressure pain tolerance threshold (PPTol) were used as responses to pressure (test) stimuli and were assessed in the right masseter muscle and left forearm before and during TMJ stimulation in addition to the CS (during, immediately after, and 10 minutes after CS). PPT and PPTol were analyzed by multilevel analysis of variance. RESULTS: The parameters were not dependent on gender, assessment site, or session, but were dependent on time (PPT, PPTol: P < .001) with session-time interactions (PPT: P < .001, PPTol: P = .002). CS triggered increases in PPT and PPTol (hypoalgesia) in both sessions and without significant differences between sessions or assessment sites during CS (painful session: 49.2 ± 3.7%, control session: 46.0 ± 3.4% for PPT and painful session: 17.7 ± 3.2%, control session: 21.4 ± 3.5% for PPTol). CONCLUSION: Acute noxious stimulation of the TMJ does not alter the magnitude of CPM effects on masseter muscle pain in either gender. It is suggested that deficiencies in CPM in persistent pain conditions are most likely more related to the duration of clinical pain than the pain per se.

Methemoglobinemia Induced by Prilocaine in a Child With Noonan Syndrome.

Limited information is currently available on methemoglobinemia caused by the administration of prilocaine in children undergoing dental procedures in Japan. This case report presents the development of methemoglobinemia due to prilocaine overdose. The patient was a female aged 5 years 8 months with Noonan syndrome who also had pulmonary valve stenosis and hypertrophic cardiomyopathy. She presented with severe dental caries affecting 12 total teeth and required general anesthesia due to a lack of cooperation during dental treatment. General anesthesia was performed, during which 3% prilocaine with 0.03 IU/mL felypressin was administered intraoperatively via infiltration. Her SpO2 gradually decreased after 30 minutes, and cyanosis was observed postoperatively. Several assessments including a 12-lead electrocardiogram, an anteroposterior chest radiograph, and venous blood gas analysis were performed to identify potential causes. However, there were no indications of acute respiratory or cardiovascular abnormalities. It was noted that a total of 192 mg prilocaine was administered during the procedure, and methemoglobinemia was suspected to have developed because of overdose. Further testing revealed an elevated serum methemoglobin of 6.9%, supporting methemoglobinemia as the cause of her decreased SpO2. In dental procedures that require the use of prilocaine to treat multiple teeth, particularly for pediatric patients, it is important to carefully manage prilocaine dosing, as an overdose may lead to methemoglobinemia.

Acute postoperative pain after orthognathic surgery can be predicted by the preoperative evaluation of conditioned pain modulation and pain catastrophizing.

INTRODUCTION: The incidence and severity of chronic postoperative pain (POP) are major clinical challenges, and presurgical conditioned pain modulation (CPM) and pain catastrophizing scale (PCS) assessments have exhibited predictive values for POP. However, whether CPM and PCS assessments are also predictive of acute POP is unknown. OBJECTIVES: We aimed to investigate the relationship between preoperative CPM and PCS and acute POP severity after orthognathic surgery by assessing preoperative CPM and PCS in 43 patients. METHODS: The pressure pain threshold and tonic painful cold-heat pulse stimulation (applied with a pain intensity score of 70 on a visual analogue scale [VAS 0-100]) were used as the test and conditioning stimuli, respectively. The pain area under the postoperative VAS area under the curve (VASAUC) was estimated. The associations between CPM, PCS, and VASAUC were also analyzed. RESULTS: No patient experienced chronic POP after 1 month. Negative and positive CPM effects (test stimulus threshold was 0% > and 0% ≤ during conditioning stimulation, respectively) were detected in 36 and 7 patients, respectively. For patients with negative CPM effects (CPM responders), multiple regression analysis revealed a prediction formula of log (VASAUC) = (-0.02 × CPM effect) + (0.13 × PCS-magnification) + 5.10 (adjusted R 2 = 0.4578, P = 0.00002, CPM effect; P = 0.002, PCS-magnification; P = 0.0004), indicating that a weaker CPM and higher PCS scores were associated with more acute POP after surgery. CONCLUSION: CPM and PCS can predict acute POP after orthognathic surgery.

Conditioned pain modulation evoked by different intensities of mechanical stimuli applied to the craniofacial region in healthy men and women.

AIMS: To investigate systematically whether conditioned pain modulation (CPM) evoked by tonic mechanical stimuli applied to the craniofacial region is intensity-, assessment site-, and gender-dependent. METHODS: Twenty healthy men and 20 women participated in four sessions. Tonic painful mechanical stimulation was applied to pericranial muscles by a mechanical headband pressure device. The pressures applied to four probes were adjusted via pain feedback from a 0 to 10 electronic visual analog scale (VAS) to generate different pain levels (VAS0, VAS1, VAS3, or VAS5) for 10 minutes. Pressure pain thresholds (PPTs) and pressure pain tolerance thresholds (PPTols) were assessed from right masseter muscle and left forearm by pressure algometry before, during, immediately after, 10 minutes after, and 20 minutes after the conditioning stimulus (CS). Data were analyzed with multilevel ANOVAs. RESULTS: PPT values normalized to baseline recordings were not dependent on gender or assessment site, but dependent on intensity (P < .001) and time (P < .001). The most painful CS (VAS5) was associated with the highest PPT increases (32.6% ± 3.3%, mean value for the two assessment sites and two genders) during CS compared to all other intensities of CS (P < .001). PPTol values normalized to baseline recordings were also not dependent on gender or assessment site, but dependent on intensity (P < .001) and time (P < .001). The most painful CS (VAS5) was associated with higher PPTol increases (11.2% ± 2.8%, mean value for the two assessment sites and two genders) during CS (P < .001). CONCLUSION: CPM evoked by mechanical stimulation of the craniofacial region is intensity-dependent but not assessment site- or gender-dependent.

Heterotopic CO2 laser stimulation inhibits tooth-related somatosensory evoked potentials.

BACKGROUND: The diffuse noxious inhibitory control (DNIC) effect is the neurophysiological basis for the phenomenon that heterotopic "pain inhibits pain" in remote areas of the body. The effect of DNIC is mediated by spino-bulbo-spinal loops and a final postsynaptic inhibitory mechanism. The DNIC effect depends on intensity, duration, quality, and application site of conditioning stimulation and stimulated nerve fiber-type. DNIC induced by CO(2) laser conditioning stimulation has, however, not yet been investigated, and the present study was designed to examine this. METHODS: As the indicator of test stimulation, the late component of somatosensory evoked potentials (SEPs) induced by electrical tooth stimulation and pain intensity were examined under CO(2) laser conditioning stimulation. As the conditioning stimuli, CO(2) laser energy (lambda = 10.6 microm, spot size Ø = 2 mm) was applied to the dorsum of the left hand. RESULTS: The maximum reductions in SEP amplitude and pain intensity evaluated using a visual analog scale were 34.7% and 28.7%, respectively during CO(2) laser conditioning stimulation. No aftereffect was observed. CONCLUSION: The present study revealed that CO(2) laser radiation attenuated the late component of SEPs induced by electrical tooth stimulation, triggering the DNIC effect but with no aftereffect.

Effects of cognitive behavioral therapy on orofacial pain conditions.

Numerous studies have confirmed the effectiveness of cognitive behavioral therapy (CBT) for chronic pain, and it is generally regarded as an appropriate intervention. However, it may not be effective for some pain sites, and the duration of the effect may be limited. In addition, some studies of CBT lacked a comparison group. This review summarizes evidence for the effectiveness of CBT for orofacial pain and assists in the development of guidelines for orofacial pain management. A literature search in PubMed was performed for studies published from April 1990 through March 2020. The search keywords were "burning mouth syndrome," "temporomandibular disorders," "myofascial pain syndrome,""chronic orofacial pain conditions," "cognitive behavioral therapy," and "non-pharmacological therapy." The results indicate that CBT alone or in combination with other treatments, such as intraoral appliance, stress management, or biofeedback, is effective for the vast majority of orofacial pain cases. Therefore, dentists should consider using CBT to manage orofacial pain in their patients.

The relation between epinephrine concentration and the anesthetic effect of lidocaine iontophoresis.

We assessed the effect of epinephrine at various concentrations on the anesthetic effect during lidocaine iontophoresis. A solution of 2% lidocaine with epinephrine in concentration of 1:80,000, 1:160,000, 1:320,000, 2% lidocaine plain and normal saline control was delivered to the medial antecubital skin for 10 minutes by iontophoresis with 1.0 mA of direct current. The pinprick test and the von Frey test were conducted to evaluate anesthetic effect. Pricking pain using visual analogue scale was significantly lower throughout the entire experiment compared with the baseline values and lasted for 60 minutes in groups with 1:80,000 and 1:160,000 epinephrine. The pressure pain thresholds (PPT) and the touch thresholds (TT) were significantly elevated in groups with 1:80,000 and 1:160,000 epinephrine compared with the baseline values. No significant elevations in the PPT and TT values were observed in the other groups. The present study revealed that the anesthetic effect was significantly enhanced in an epinephrine dose-related manner and the anesthetic effect of 2% lidocaine with 1:160,000 epinephrine was equivalent to the same anesthetic with 1:80,000 epinephrine.

Somatosensory assessment and conditioned pain modulation in temporomandibular disorders pain patients.

The pathophysiology and underlying pain mechanisms of temporomandibular disorders (TMD) are poorly understood. The aims were to assess somatosensory function at the temporomandibular joints (TMJs) and to examine whether conditioned pain modulation (CPM) differs between TMD pain patients (n = 34) and healthy controls (n = 34). Quantitative sensory testing was used to assess the somatosensory function. Z-scores were calculated for patients based on reference data. Conditioned pain modulation was tested by comparing pressure pain thresholds (PPTs) before, during, and after the application of painful and nonpainful cold stimuli. Pressure pain thresholds were measured at the most painful TMJ and thenar muscle (control). Data were analyzed with analyses of variance. Most (85.3%) of the patients exhibited at least 1 or more somatosensory abnormalities at the most painful TMJ with somatosensory gain with regard to PPT and punctate mechanical pain stimuli, and somatosensory loss with regard to mechanical detection and vibration detection stimuli as the most frequent abnormalities. There was a significant CPM effect (increased PPT) at both test sites during painful cold application in healthy controls and patients (P < 0.001). There was no significant difference in the relative CPM effect during painful cold application between groups (P = 0.227). In conclusion, somatosensory abnormalities were commonly detected in TMD pain patients and CPM effects were similar in TMD pain patients and healthy controls.

Thermal application modulates orofacial somatosensory perception in healthy men and women.

OBJECTIVE: To test if orofacial somatosensory perception can be modulated by experimental thermal application in healthy human. METHODS: Twelve men and twelve age-matched women participated. In each session thermal application with 10, 42 or 32°C (cooling, warming, control) was applied to the skin over the right masseter using a thermode. Quantitative sensory testing was performed at the skin over the right (testing side) and left (contralateral side) masseter before, during, after the thermal application. RESULTS: During the cooling, mechanical detection threshold (MDT), mechanical pain threshold (MPT) and pressure pain threshold (PPT) were increased, and mechanical pain sensitivity was decreased at testing side compared with baseline (P<0.005). The MPT and PPT at the contralateral side were also increased (P<0.004). During the warming and control, the MDT was increased at the testing side compared with baseline (P=0.002). The somatosensory sensitivity was decreased during cooling compared to warming and control (P<0.05). No gender differences were found. CONCLUSIONS: This study shows an ipsilateral decrease of cutaneous sensation or pain sensitivity during cooling without gender differences. In addition, hypoalgesia on the contralateral side suggests a central mode of action. SIGNIFICANCE: The results support clinical experiences that cooling may alleviates pain both locally and generally.

Effect of conditioned pain modulation on trigeminal somatosensory function evaluated by quantitative sensory testing.

The aim of the study was to systematically investigate the effect of craniofacially evoked conditioned pain modulation on somatosensory function using a quantitative sensory testing (QST) protocol applied to the trigeminal area in healthy humans. Pressure pain evoked by a mechanical compressive device was applied as conditioning stimulus (CS) in the craniofacial region, with a pain intensity of 5 on a visual analogue scale (VAS: 0-10 cm) (painful session) or with VAS score of 0 (control session). A full QST battery of 13 parameters was performed as test stimuli on the dominant-side cheek. The individual QST data from 11 men and 12 women were transformed into z scores, and the QST data and z scores were tested using analyses of variance. Analyses of variance of pressure pain threshold (PPT) data (log-transformed values and z scores) indicated significant session (P ≤ .003) and time (P < .001) effects with a session-time interaction (P < .001), but no main effect of sex (P ≥ .053, effect size ≥ .166). The session-time interaction showed that the PPTs in the painful session were associated with significantly higher log-transformed PPT values and significantly lower z scores compared with the control session at the time point during CS (hypoalgesia) (P < .001). No other QST parameters were significantly modulated by the CS. Sex differences were not detected in this study; a larger sample size may be needed to further explore this possibility. However, the findings indicate that when extensive QST protocols are applied, PPT may be the most sensitive measure to detect endogenous pain inhibitory mechanisms.

The inter- and intra-individual variance in descending pain modulation evoked by different conditioning stimuli in healthy men.

Background and purpose Conditioned pain modulation (CPM) is a phenomenon in which pain is inhibited by heterotopic noxious stimulation. It is not known how the experimental condition affects the magnitude of the CPM response and the inter-and intra-individual variations. It is important to get the information of the test-retest reliability and inter-individual variations of CPM to apply CPM as a diagnostic tool or for screening analgesic compounds. This study evaluated (1) the magnitude of CPM, (2) the inter-individual coefficient of variation (inter-CV) and (3) the intra-individual coefficient of variation (intra-CV) to (A) different stimulus modalities to evoke CPM and (B) different assessment sites. Methods Twelve healthy men (age 19-38 years) participated in this study. Cold pressor pain (CPP) (immersing the hand into cold water), tourniquet pain (cuff around the upper arm) and mechanical pressure pain (craniofacial region) were used in randomized order as conditioning stimuli (CS). The test stimulus (TS) was pressure pain applied to the right masseter muscle, left forearm and leg (bilateral tibialis anterior: TA). The responses were pressure pain thresholds (PPT), pressure pain tolerance (PPTol) thresholds and the pain intensity which was assessed on a visual analogue scale (VAS, 0-10 cm) following 1.4 and 1.6 × PPT applied to TA. The TS was applied before, during and 10 min after the CS. The intra-individual CV was estimated between different days. Results CPP induced the most powerful CPM on PPT (66.3 ± 10.0% increase), VAS ratings (41.5 ± 5.3% reduction) and PPTol (32.6±4.6% increase), especially at TA, and resulted in the smallest inter-CV (41.4-60.1%). Independently of the CS, the inter-CV in general showed that the recordings from the orofacial region and the forearm had smaller values than from the leg. The smallest intra-CV value was obtained in pain ratings with CPP (27.0%). Conclusions This study suggests that (1) the CPP evokes the largest CPM, (2) the leg as the assessment site results in the largest CPM responses and (3) the CPP causes the smallest inter- and intra-CV. Implication The present investigation implicates that the CPP is the most efficient conditioning stimulus to induce CPM when assessed by pressure pain thresholds.

Diffuse noxious inhibitory controls triggered by heterotopic CO2 laser conditioning stimulation decreased the SEP amplitudes induced by electrical tooth stimulation with different intensity at an equally inhibitory rate.

The purpose of this study was to investigate (1) whether selective Adelta-fiber stimulation with CO(2) laser produces a diffuse noxious inhibitory controls (DNIC) effect in the trigeminal nerve territory; and (2) whether the DNIC effect differs depending on test stimulus intensities under constant conditioning stimuli. To examine whether the CO(2) laser radiation on the dorsum of the hand selectively stimulates Adelta-fibers, laser evoked potentials (LEP) were recorded. The mean peak latency of LEP was 381.4 ms. The findings revealed that the CO(2) laser selectively stimulated Adelta-fibers. Electrical tooth stimuli with 3 levels of intensities (1.2, 1.4, 1.6 times the pain threshold) were applied to subjects as test stimulation in randomized order, with a CO(2) laser stimulus of 18 mJ/mm(2) applied to the dorsum of the hand for 4 min as the noxious conditioning stimulus. Somatosensory evoked potentials (SEP) induced by electrical tooth stimulation were recorded and tooth pain intensity was evaluated using a visual analogue scale (VAS). The amplitudes of the SEP late component and VAS values were significantly decreased only during the conditioning stimuli without aftereffect. The inhibitory rates of the amplitudes ranged from 31.3% to 34.6% and the VAS values from 29.0% to 31.2%. There were no significant differences in their inhibitory rates between the 3 test stimulus intensities. The result indicated that selective Adelta-fiber stimulation with the CO(2) laser produces a DNIC effect in the trigeminal nerve territory and suggested that the DNIC effect does not depend on the intensity of the test stimuli.