Pain Threshold Tolerance Research Articles

User-independent assessment of conditioning pain modulation by cuff pressure algometry.

The use of conditioning pain modulation (CPM) is hampered by poor reproducibility and lack of user-independent paradigms. This study refined the CPM paradigm by applying user-independent cuff algometry. In 20 subjects, the CPM effect of conditioning with cuff stimulation on the arm was investigated by pain test stimuli on the contralateral leg before and in parallel with different cuff conditionings (10, 30, 60kPa/60s; 30, 60kPa/10s). As test stimulus, another cuff was inflated (1kPa/s) until the subjects detected the pain tolerance threshold (PTT) during which the pain detection threshold (PDT) and the pressure at a pain intensity of 6 cm on a 10-cm visual analogue scale (PVAS6) were extracted. For comparison, pressure pain thresholds (PPTs) as test stimuli were recorded by the user-dependent handheld pressure algometry. Combinations of cuff locations for conditioning (pain intensity standardized) and contralateral test stimuli were additionally evaluated (leg-arm, leg-leg, arm-thigh). The test-retest reliability in two sessions 1month apart was assessed in five CPM protocols. In all protocols, the PDT, PVAS6 and PTT increased during conditioning compared with baseline (p<0.05). The CPM effect (i.e. conditioning minus baseline) for PVAS6, PTT and PPT increased for increasing conditioning intensities (p<0.05). The CPM effects were not significantly different for changes in conditioning durations or conditioning/test stimulus locations. In two sessions, the CPM effects for PVAS6 and PTT assessed after 60s of conditioning on the leg/thigh showed the highest intra-class correlations (0.47-0.73), where they were 0.04-0.6 for PPTs. The user-independent cuff algometry is reliable for CPM assessment and for supra-pain threshold test stimuli better than the user-dependent technology. A user-independent CPM technique where the conditioning is controlled by one cuff stimulation, and the test-stimulus is provided by another cuff stimulation. This study shows that cuff algometry is reliable for CPM assessment.

Physiological and Psychological Predictors of Short-Term Disability in Workers with a History of Low Back Pain: A Longitudinal Study.

Despite an elusive pathophysiology, common characteristics are often observed in individuals with chronic low back pain (LBP). These include psychological symptoms, altered pain perception, altered pain modulation and altered muscle activation. These factors have been explored as possible determinants of disability, either separately or in cross-sectional studies, but were never assessed in a single longitudinal study. Therefore, the objective was to determine the relative contribution of psychological and neurophysiological factors to future disability in individuals with past LBP. The study included two experimental sessions (baseline and six months later) to assess cutaneous heat pain and pain tolerance thresholds, pain inhibition, as well as trunk muscle activation. Both sessions included the completion of validated questionnaires to determine clinical pain, disability, pain catastrophizing, fear-avoidance beliefs and pain vigilance. One hundred workers with a history of LBP and 19 healthy individuals took part in the first experimental session. The second experimental session was exclusively conducted on workers with a history of LBP (77/100). Correlation analyses between initial measures and disability at six months were conducted, and measures significantly associated with disability were used in multiple regression analyses. A first regression analysis showed that psychological symptoms contributed unique variance to future disability (R2 = 0.093, p = .009). To control for the fluctuating nature of LBP, a hierarchical regression was conducted while controlling for clinical pain at six months (R2 = 0.213, p < .001) where pain inhibition contributed unique variance in the second step of the regression (R2 change = 0.094, p = .005). These results indicate that pain inhibition processes may constitute potential targets for treatment to alleviate future disability in individuals with past or present LBP. Then again, the link between psychological symptoms and pain inhibition needs to be clarified as both of these factors are linked together and influence disability in their own way.

Efficacy of Acupuncture Treatment on Myofascial Pain Syndrome in Upper Trapezius

Upper trapezius myofascial pain syndrome is one of the most common musculoskeletal impairments. Hyper-irritable pain can be intensified due to muscle contraction either at rest or during movement. In traditional Chinese medicine, the Jian Jing (GB21) acupoint is most commonly used to treat pain, neck stiffness, shoulder tension, and headaches. Subjects were recruited for this study at the local outpatient center and randomly assigned into an experimental group with 40-mm-long acupuncture needling or a placebo group with 2.5-mm-long auricular needling. A pressure pain algometer was used to measure the pressure pain threshold (PPT) before and after needling, and two sets of electromyography (EMG) electrodes were attached on both shoulders to measure the trapezius muscle activity during a shoulder shrug motion. The PPT and EMG data were recorded and analyzed to compare different needling depths in suppressing the muscular pain. Twenty-four participants completed the 3-week experiment. The outcomes indicated that there was no substantial difference in PPT pre- and post-treatment between groups. The root-mean-square and integrated EMG activities showed significant decreases during the shrugging motion after each 20-mm-deep acupuncture treatment for the experimental group, but not in the placebo group with the 2.5-mm-deep surface acupuncture. Although the pain tolerance threshold showed a tendency towards improvement, it was not statistically significant, while the placebo group showed almost no treatment effect. Comparing the effects of insertion depth i.e., acupuncture and auricular surface needling, the EMG data indicate that deep acupuncture is an effective treatment for the management of trapezium myofascial pain as it can ameliorate the muscle fatigue of the upper trapezius due to prolong unchanged posture.

Comparing test–retest reliability and magnitude of conditioned pain modulation using different combinations of test and conditioning stimuli

This study aimed to compare the reliability and magnitude of conditioned pain modulation (CPM) by applying different test stimuli (TS) and conditioning stimuli (CS). Twenty-six healthy male participants were recruited in the study of two identical sessions. In each session, four TS (electrical, heat, handheld, and cuff pressure algometry) were applied before and during CS (cold pressor test (CPT) or cuff algometry). The same procedure was repeated with 45-min intervals, but with the other CS. Five thresholds were measured including four pain detection thresholds from four TS and pain tolerance threshold from cuff TS (cuff PTT). Intraclass correlation coefficient (ICC (3,1)) and coefficient of variation (CV) were calculated as measures of reliability. The reliability of TS before and during CS was good for all combinations (ICC: 0.60–0.96, CV: 2.2–22.9%), but the reliability of the CPM effect varied (ICC: 0.04–0.53, CV: 63.6–503.9%). The most reliable combinations were considered to be the handheld pressure pain threshold with CPT (ICC: 0.49, CV: 63.6%) and the cuff pressure pain threshold with CPT (ICC: 0.44, CV: 107.6%). Significant CPM effects were found for all combinations, except the combinations of electrical and heat pain thresholds with cuff CS, which indicates the novel classification of the CPM mechanism. The combinations of handheld pressure and heat pain threshold with CPT would provide the minimum sample size to detect the significant CPM changes in further studies. It is beneficial to provide and compare both ICC and CV to design further clinical trials.

Pain Intensity and Opioid Utilization in Response to CPAP Therapy in Veterans with Obstructive Sleep Apnea on Chronic Opioid Treatment.

Sleep fragmentation has been linked to poor pain tolerance and lowered pain threshold. Little evidence exists on whether continuous positive airway pressure (CPAP) adherence in veterans with obstructive sleep apnea (OSA) who are taking opioids for non-malignant pain would ameliorate pain and reduce consumption of opioids. A retrospective case-control study was performed at a VA sleep center. Pain intensity was assessed using the Numerical Categorical Scale prior to CPAP treatment and 12-mo follow-up. Opioids intake was assessed using the morphine equivalent daily dose (MEDD). Adherence to CPAP was evaluated with the built-in meter. We reviewed 113 patients with OSA (apnea-hypopnea index [AHI] 35.9 ± 29.5) using a MEDD of 61.6 mg (range 5-980 mg) and a control group of 113 veterans with OSA (AHI 33.4 ± 27.3) on no opioids treatment. CPAP adherence was significantly lower at 12 mo in opioid-treated patients compared to controls (37% versus 55%; p = 0.01). Greater pain intensity was the only independent variable associated with CPAP non-adherence at 12-mo follow-up (p = 0.03). Compared to baseline, no significant difference was observed in pain intensity or consumption of opioids in CPAP adherent patients. CPAP treatment did not reduce pain intensity or consumption of opioids in veterans with chronic pain who have coexisting OSA. CPAP adherence was lower in opioid-treated veterans with OSA compared to opioid-free veterans with OSA. Pain intensity was the only determinant of CPAP adherence. Future studies are needed to evaluate pain management program on adherence to CPAP.

A randomized, double-blind, positive-controlled, 3-way cross-over human experimental pain study of a TRPV1 antagonist (V116517) in healthy volunteers and comparison with preclinical profile.

This experimental, translational, experimental pain, single-center, randomized, double-blind, single-dose, 3-treatment, 3-period cross-over proof-of-concept volunteer trial studied the efficacy of a novel TRPV1 antagonist (V116517) on capsaicin- and UV-B-induced hyperalgesia. Heat and pressure pain thresholds, von Frey stimulus-response functions, and neurogenic inflammation were assessed together with safety. Each treatment period was 4 days. The 3 single oral treatments were 300 mg V116517, 400 mg celecoxib (a COX-2 inhibitor), and placebo. The heat pain detection and tolerance thresholds were increased significantly (P < 0.0001) by V116517. Heat pain detection and tolerance thresholds showed significantly less capsaicin hyperalgesia after V116517 (P = 0.004 and P < 0.0001, respectively). Celecoxib reduced UV-B-provoked pressure pain sensitization (P = 0.01). Laser Doppler flowmetry and erythema index after UV-B were significantly (P < 0.0001) reduced by celecoxib. Stimulus-response function in capsaicin-treated areas showed significant differences between both celecoxib and placebo and between V116517 and placebo. The body temperature showed no change, and no side effects were reported for any of the treatments. The TRPV1 antagonists and the COX-2 inhibitor showed different antihyperalgesic profiles indicating different clinical targets. In addition, the preclinical profile of V116517 in rat models of UV-B and capsaicin-induced hypersensitivity was compared with the human experimental data and overall demonstrated an alignment between 2 of the 3 end points tested. The TRPV1 antagonist showed a potent antihyperalgesic action without changing the body temperature but heat analgesia may be a potential safety issue.

Association between Gene Polymorphisms and Pain Sensitivity Assessed in a Multi-Modal Multi-Tissue Human Experimental Model - An Explorative Study.

The genetic influence on sensitivity to noxious stimuli (pain sensitivity) remains controversial and needs further investigation. In the present study, the possible influence of polymorphisms in three opioid receptor (OPRM, OPRD and OPRK) genes and the catechol-O-methyltransferase (COMT) gene on pain sensitivity in healthy participants was investigated. Catechol-O-methyltransferase has an indirect effect on the mu opioid receptor by changing its activity through an altered endogenous ligand effect. Blood samples for genetic analysis were withdrawn in a multi-modal and multi-tissue experimental pain model in 40 healthy participants aged 20-65. Seventeen different single nucleotide polymorphisms in different genes (OPRM, OPRK, OPRD and COMT) were included in the analysis. Experimental pain tests included thermal skin stimulation, mechanical muscle and bone stimulation and mechanical, electrical and thermal visceral stimulations. A cold pressor test was also conducted. DNA was available from 38 of 40 participants. Compared to non-carriers of the COMT rs4680A allele, carriers reported higher bone pressure pain tolerance threshold (i.e. less pain) by up to 23.8% (p < 0.015). Additionally, carriers of the C allele (CC/CT) of OPRK rs6473799 reported a 30.4% higher mechanical visceral pain tolerance threshold than non-carriers (TT; p < 0.019). For the other polymorphisms and stimulations, no associations were found (all p > 0.05). In conclusion, COMT rs4680 and OPRK rs6473799 polymorphisms seem to be associated with pain sensitivity. Thus, the findings support a possible genetic influence on pain sensitivity.

Pain Tolerance and Pain Threshold According to Sport and Sex

Pain Tolerance and Pain Threshold According to Sport and Sex

Determining Pain Detection and Tolerance Thresholds Using an Integrated, Multi-Modal Pain Task Battery.

Human pain models are useful in the assessing the analgesic effect of drugs, providing information about a drug's pharmacology and identify potentially suitable therapeutic populations. The need to use a comprehensive battery of pain models is highlighted by studies whereby only a single pain model, thought to relate to the clinical situation, demonstrates lack of efficacy. No single experimental model can mimic the complex nature of clinical pain. The integrated, multi-modal pain task battery presented here encompasses the electrical stimulation task, pressure stimulation task, cold pressor task, the UVB inflammatory model which includes a thermal task and a paradigm for inhibitory conditioned pain modulation. These human pain models have been tested for predicative validity and reliability both in their own right and in combination, and can be used repeatedly, quickly, in short succession, with minimum burden for the subject and with a modest quantity of equipment. This allows a drug to be fully characterized and profiled for analgesic effect which is especially useful for drugs with a novel or untested mechanism of action.

(494) Optimizing resilience in orofacial pain and nociception (ORION): exploring the efficacy of a hope intervention for pain

Resilience is a dynamic process resulting in positive adjustment and adaptation after exposure to adversity. In recent years, there has been growing interest in the contribution of positive psychological factors to pain and pain-related coping; however, interventions built upon bolstering resilience have received less attention. Hope is a strength-based motivational state consisting of one’s belief in their ability to generate routes to achieve goals (pathways) and initiating directional activity towards attaining goals (agency). Emerging evidence supports the role of hope in psychosocial adjustment and adaptive pain coping, suggesting that approaches designed to foster hope and personal strengths may enhance pain adaptation. Therefore, the overall objective of this pilot study was to test the feasibility and efficacy of a resilience-oriented hope intervention for clinical pain, as well as psychosocial outcomes and experimental pain sensitivity in individuals with orofacial pain. Twenty-three participants (78% female) with temporomandibular disorder were randomized to a 3-session intervention intended to increase hope or a control intervention involving education about pain and stress. Prior to and after the intervention, participants attended two laboratory sessions whereby they completed psychosocial questionnaires and sensitivity to heat, cold, and pressure pain was assessed. Hope was measured by the Adult State Hope Scale. Results indicated that higher levels of hope were associated with greater pressure pain thresholds at all sites: temporalis, masseter, temporomandibular joint [TMJ], forearm, trapezius, tibialis anterior (r’s=.31-.49; p’s<.03). Compared to Pain Education, the Hope group exhibited an increase in hope, reductions in pain catastrophizing, as well as greater increases in heat pain tolerance and pressure pain thresholds at the tibialis anterior and TMJ. Although preliminary, these results suggest that resilience-oriented interventions may be beneficial in reducing pain and catastrophizing and could serve as a target for pain management. Funded by the APS Sharon S. Keller Chronic Pain Research grant.

Preoperative pain mechanisms assessed by cuff algometry are associated with chronic postoperative pain relief after total knee replacement.

Chronic postoperative pain after total knee replacement (TKR) in knee osteoarthritis (KOA) implies clinical challenges. Widespread hyperalgesia, facilitated temporal summation of pain (TSP), and impaired conditioned pain modulation (CPM) have been found in painful KOA. This exploratory study investigated postoperative pain relief 12 months after TKR in 4 subgroups of patients preoperatively profiled by mechanistic quantitative sensory testing. In 103 patients with KOA, pressure pain detection threshold (PDT) and tolerance thresholds (PTT) were assessed at the lower leg using cuff algometry. Temporal summation of pain was measured as an increase in pain intensity scores during 10 repeated (2 seconds intervals) painful cuff stimuli. Conditioned pain modulation was calculated as the relative increase in PDT during painful conditioning stimulation. The grand averages of TSP and CPM were calculated and values below or above were used for subgrouping: facilitated TSP/impaired CPM (group A, N = 16), facilitated TSP/normal CPM (group B, N = 15), normal TSP/impaired CPM (group C, N = 44), and normal TSP/normal CPM (group D, N = 28). Clinical VAS pain intensity scores were collected before and 12 months after TKR surgery and the pain relief calculated. Less pain relief was found in group A (52.0% ± 14.0% pain relief) than in group B (81.1% ± 3.5%, P = 0.023) and group C (79.6% ± 4.4%, P = 0.007), but not group D (69.4% ± 7.9%, P = 0.087). Low preoperative PDT was associated with a less postoperative pain relief (R = -0.222, P = 0.034), whereas TSP or CPM alone showed no associations with postoperative pain relief. This explorative study indicated that patients with osteoarthritis with facilitated TSP together with impaired CPM are more vulnerable to experience less pain relief after TKR.

Alterations in Pain Responsiveness and Serum Biomarkers in Juvenile Myoclonic Epilepsy: an Age- and Gender-Matched Controlled Pilot Study

Introduction: Serum levels of several biomarkers along with sensory responsiveness were investigated in juvenile myoclonic epilepsy patients in comparison with healthy controls. Methods: Ten epileptic patients (36.1 ± 3.4 years) and ten gender- and age-matched healthy controls were recruited. Mechanical sensitivity, cold pressor tolerance and serum levels of BDNF, CGRP, PGE2, S100B and TNF-α were investigated. Results: Mechanical sensitivity to pinprick was lower in patients (p &lt; 0.05) while cold pain tolerance threshold was higher. Serum level of BDNF was higher in patients compared with controls (p &lt; 0.01). The same pattern was evident for CGRP (p &lt; 0.05). Serum level of PGE2 was lower in patients (p &lt; 0.01). Conclusion: Juvenile myoclonic epilepsy patients had an altered serum biomarker pattern and sensory perception in comparison with controls.

Influência da neuropatia diabética no comportamento de respostas biomecânicas e sensorials no andar em esteira rolante

Biomechanical investigation of the human movement has been bringing important discussions about the musculoskeletal system functions and the control of movement. The human walking is one of the most studied motor behaviors and its mechanical aspects contribute to characterize, identify, and intervene in pathological conditions. Dynamic, kinematic, and electromyographic analyses of pathological gait can significantly help the comprehension of the control mechanism of gait and its compensatory alterations. These analyses can also contribute to therapeutic and preventive interventions in patients whose walking behavior is altered due to some disease that accomplish the neuromotor system. In the present study, we described and interpreted self-cadence walking in a treadmill of neuropathic diabetic subjects under biomechanical considerations, such as dynamic, temporal, spatial, and electromyographic analysis during stance phase. We also studied sensorial and motor aspects in order to characterize the neuropathic and control subjects. The somatossensorial responses and pain tolerance threshold in the neuropathic subjects were significantly higher and considered away from the normal patterns. The self-cadence and the treadmill velocity were significantly lower in neuropathic gait. Single and double stance time, stride and step length were significantly higher during neuropathic gait. The neuropathic subjects showed lower vertical force peaks and lower deflections of vertical force and those findings were secondary consequences of the conservative strategy of lowering the gait velocity adopted by the neuropathic in order to reach a more stable locomotor pattern. The electromyographic responses of the thigh and leg muscles in neuropathic subjects showed lower magnitudes and were delayed paring to the normal recruitment pattern, specially the anteriortibialis muscle right and left. These findings lead us to conclude that probably central and/or peripheral control mechanisms of the gait of neuropathic diabetic patients are altered due to somatossensorial and motor deficits. The mechanism of load reduction during walking was considered inefficient because of the activation delay of the lateral vastus and anterior tibialis muscles. We conclude that the peripheral diabetic neuropathy damages not only somatossensorial and motor sources but also intrinsic mechanisms of motor control leading to alterations in the ankle efficiency in gait. This resulting distal inefficiency compromises some of the principal requirements to gait, which are progression and balance.

Validation of simple and inexpensive algometry using sphygmomanometer cuff and neuromuscular junction monitor with standardized laboratory algometer.

Background and Aims:The availability, ergonomics and economics prohibit the routine use of algometers in clinical practice and research by the anesthesiologists. A simple bedside technique of quantitative pain measurement would enable the routine use of algometry. We proposed to validate simple pain provocation using sphygmomanometer cuff and the electric stimulation of neuromuscular junction monitor (TOF-guard, Organon Teknika) to measure pain against a standardized laboratory pressure algometer.Material and Methods:Pain detection threshold (Pdt) and pain tolerance threshold (Ptt) were measured in forty healthy volunteers of both genders, using the above three techniques. All measurements were repeated three times. The co-efficient of inter-rater reliability (or consistency) between three independent measurements obtained from each of the techniques was determined by Cronbach's co-efficient alpha (α C). The correlation between the mean Pdt and Ptt values recorded by standardized algometer and the sphygmomanometer technique and nerve stimulator technique was performed using Pearson Correlation. An r >0.5 and a two-tailed significance of <0.05 were considered as good correlation between the standardized algometer and the tested techniques.Results:There was a good inter-rater reliability (α C > 0.7) for the three techniques. There was a good correlation with r >0.65 (P < 0.001) between the measurements of standardized pressure algometer and the two techniques being tested as alternatives for algometer to measure pain.Conclusion:The sphygmomanometer cuff technique and electrical stimulation with the peripheral nerve stimulator to measure pain threshold and tolerance provide a simple, efficient, repeatable measure of pain intensity and can be used as suitable alternatives to standard algometers.

Sickle Cell Disease Patients Show Sensitization of Myelinated Sensory Nerve Fibers

There is increasing evidence that many patients with sickle cell disease (SCD) develop chronic pain in addition to experiencing acute pain secondary to vaso-occlusive episodes (VOE). Those patients who develop chronic pain often exhibit features suggestive of neuropathic processes such as allodynia and pain "shooting" or "tingling" in character. Using electrophysiologic techniques in ex-vivo nerve-skin preparations and nocifensive behavior studies in sickle cell mouse models, we and others have shown that SCD is associated with sensitization of light touch cutaneous sensory fibers, and decreased threshold in response to 2000Hz and 250 Hz electrical sine wave stimulation. These findings are indicative of Aβ and Ad fibers sensitization and in turn compatible with neuropathic process.We hypothesized that the same phenomena of nerve fiber sensitization in the mouse model would be observed in SCD patients. This hypothesis was tested using an experimental paradigm with sine-wave electrical stimulation delivered at three different frequencies: 2000, 250, and 5 Hz, which preferentially stimulate Aβ, Ad, and C fibers, respectively. Thermal and mechanical sensory testing was also performed. After IRB approval, SCD subjects with high (≥ than 3 ER visits or admissions for VOEs per year) or low (< 2 ER visits or admissions per year) pain frequency, and age- and sex-matched African-American healthy controls were recruited at baseline states during routine clinic visits. After informed consent (and/or assent) was obtained, patients underwent quantitative sensory testing (QST) that included heat and cold perception and tolerance (with a TSA II-Sensory Analyzer), mechanical (using a Wagner FDIX Force One) and current perception and pain tolerance thresholds (using the Neurometer).We enrolled 19 SCD subjects with high and 4 with low pain frequency (total 23 SCD participants), and 11 African-American non-SCD subjects who tolerated and completed all QSTs. As there was no difference between QST responses in patients with high and low pain frequency, these two groups were combined as the SCD group. We found that SCD subjects had significantly decreased cold tolerance threshold (p=0.034) and a trend towards lower thresholds for cold perception and heat tolerance, which is in concert with previously reported findings. Expanding upon these findings, SCD patients had a significantly reduced pain tolerance threshold in response to 2000 Hz stimulation (p=0.005), which preferentially stimulates Aβ fibers (see figure). These results suggest that adolescents with SCD have sensitization of myelinated Aβ fibers. Interrogation of the Ad and C fibers with 250 and 5 Hz stimulation, respectively, revealed no significant differences in tolerance thresholds among the groups, however SCD patients showed a trend toward lower thresholds in both frequencies (see figure). Combined, these findings support the use of sine-wave stimulation on the evaluation of pain phenotype in SCD and the notion that SCD subjects may have neuropathic processes contributing to their pain phenotype. TableDemographics, thermal and mechanical sensory testing in SCD and control subjects.VariableSCD (n=23)Control (n=11)Age (years)16 (15-18.8)19 (14-21)Male (%)3 (30%)11 (48%)Cold Perception (°C)29.8 (28.5-30.5)30.4 (29.9-30.9)Cold Tolerance (°C)8.5 (2.0-17.0) *0.9 (0.0-6.9)Heat Perception (°C)34.4 (33.5-35.2) *33.6 (33.2-34.1)Heat Tolerance (°C)48.9 (47.5-49.8)50.0 (45.3-50.1)Mechanical Tolerance (lbF)7.7 (5.9-9.7)9.5 (7.7-10.8)*p < 0.05. Values are shown as median and interquartile range. SCD subjects reached cold tolerance and heat perception at significantly higher temperatures as compared to controls; p=0.034 and p= 0.035, respectively. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Characteristics of the pain tolerance threshold induced by electrical stimulation of the alveolar ridge.

The purpose of this study was to determine the characteristics of the pain tolerance threshold (PTT) induced by electrical stimulation of the alveolar ridge. A total of 100 healthy volunteers studying or working at Nihon University School of Dentistry at Matsudo and patients from Nihon University School of Dentistry at Matsudo Affiliated Hospital, including 51 men (58.7 ± 17.6 years old) and 49 women (60.7 ± 17.1 years old), participated in this study. The volunteers were enrolled after obtaining written informed consent. PTT measurements were obtained using a Neurometer CPT/C® device to deliver electrical stimulation around the left greater palatine foramen at frequencies of 5 and 250 Hz. When the stimulus could no longer be tolerated, the participant released a button to automatically discontinue the stimulus. After the distribution of the PTT values was analyzed, the influence of gender, age, and Eichner index on PTT was analyzed. The Eichner index values were divided into three categories: group A (four supporting zones), group B (less than four supporting zones but with anterior tooth contact), and group C (no occlusal contact). The PTT values did not show a normal distribution. There were no significant differences in PTT between men and women. PTT was significantly associated with age (P = 0.017) at 5 Hz in men. There were no significant differences in PTT among the Eichner index groups. The characteristics of the PTT of the alveolar ridge are as follows: (1) age and PTT at 5 Hz are significantly associated with men but not with women, and (2) the Eichner index has no influence on the PTT.

The pain of a heart being broken: pain experience and use of analgesics by caregivers of patients with Alzheimer's disease.

BackgroundIt has been observed that psychical suffering (e.g. the feeling of losing a significant person) tends to reduce the physical pain tolerance threshold, as well as to increase the subjective sense of painfulness. The purpose of this study was to assess pain sensation among a group of caregivers of patients with Alzheimer’s disease, and to determine the psychological factors (emotional and relational) that contribute to both pain perception and coping with pain via the use of analgesics.MethodsThe study comprised 127 caregivers of patients with Alzheimer’s disease. Questionnaires were used to elicit pain intensity, strength of emotional relationship between caregiver and patient, sense of painfulness of the loss experienced, depression level, and somatic ailments.ResultsA large majority (87.4 %) of participants reported pain complaints, while 93 % took analgesics without a doctor’s recommendation at least once a week; 8 % took painkillers daily. The strongest predictors of both perceived pain and tendency to use analgesics were sense of loss and painfulness of loss in relation to the patient’s deteriorating condition.ConclusionsThe pain experienced by caregivers may be connected to social pain resulting from the experience of losing someone they are close to. Caregivers may resort to excessive use of analgesics as a pain-coping strategy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12888-015-0571-1) contains supplementary material, which is available to authorized users.

The genetic influences on oxycodone response characteristics in human experimental pain.

Human experimental pain studies are of value to study basic pain mechanisms under controlled conditions. The aim of this study was to investigate whether genetic variation across selected mu-, kappa- and delta-opioid receptor genes (OPRM1, OPRK1and OPRD1, respectively) influenced analgesic response to oxycodone in healthy volunteers. Experimental multimodal, multitissue pain data from previously published studies carried out in Caucasian volunteers were used. Data on thermal skin pain tolerance threshold (PTT) (n=37), muscle pressure PTT (n=31), mechanical visceral PTT (n=43) and thermal visceral PTT (n=41) were included. Genetic associations with pain outcomes were explored. Nineteen opioid receptor genetic polymorphisms were included in this study. Variability in oxycodone response to skin heat was associated with OPRM1 single-nucleotide polymorphisms (SNPs) rs589046 (P<0.0001) and rs563649 (P<0.0001). Variability in oxycodone response to visceral pressure was associated with four OPRM1 SNPs: rs589046 (P=0.015), rs1799971 (P=0.045), rs9479757 (P=0.009) and rs533586 (P=0.046). OPRM1 SNPs were not associated with oxycodone visceral heat threshold, however, one OPRD1 rs419335 reached significance (P=0.015). Another OPRD1 SNP rs2234918 (P=0.041) was associated with muscle pressure. There were no associations with OPRK1 SNPs and oxycodone response for any of the pain modalities. Associations were found between analgesic effects of oxycodone and OPRM1 and OPRD1 SNPs; therefore, variation in opioid receptor genes may partly explain responder characteristics to oxycodone.

Effect of Hydroethanolic Extract of Rubus fruticosus on Neuropathic Pain in Wistar Diabetic Rats

Article type: Original Article Background: Diabetes mellitus is the most common metabolic disorder with many complications such as neuropathic pain which relief from it is a dilemma. Objectives: To investigate the effect of hydroethanolic extract of Rubus fruticosus on neuropathic pain in diabetic rats. Materials and Methods: In this experimental case –control study, forty eight male Wistar rats (250±20 g) were divided randomly to non-diabetic and diabetic groups. Streptozotocin (60 mg/kg, intra-peritoneal) was used to induce experimental diabetes. Each group was divided into three groups: receiving orally normal saline, 100 and 200 mg/kg doses of Rubus fruticosus extract for 30 days. At the end; the rats were subjected to Tail-Flick test. The data were analyzed by one-way and two-way ANOVA followed by Tukey’s test in SPSS 21. Results: In a paired comparison, all diabetic groups had shorter latency of tailflicking time (p < 0.01) and lower pain tolerance threshold. Also among diabetic rats, significant differences existed between saline group and group receiving the extract at a dose of 100 mg/Kg (p < 0.01), between saline group and the group receiving the extract at a dose of 200 mg/Kg (p < 0.001) and also between the groups receiving extract at two different doses (p < 0.001). But, only diabetic group receiving the extract at a dose of 200 mg/Kg showed positive significant difference with non-diabetic control group (p < 0.01). Conclusions: The hydroethanolic extract of Rubus fruticosus can heighten the pain tolerance threshold and reduce the neuropathic pain induced by diabetes mellitus.

Comparison of Pain Tolerance Thresholds of Upper Limb to Identify the Most Appropriate Venipuncture Site

Venipuncture is often accompanied by pain, which can compromise dental care and foment distrust toward dental care providers. The aim of the present study was to identify sites on the forearm and hand that have the greatest pain tolerance threshold (PTT) during venipuncture. The PTT was estimated in 20 healthy volunteers using a noninvasive nerve conduction threshold device. The subjects self-stimulated 5 sites (median cubital vein, cephalic vein at the cubitus, basilic vein, cephalic vein at the carpus, and superficial dorsal vein) at 2 kHz, 250 Hz, and 5 Hz. We measured the stimulation intensity before the subject deactivated the device. Differences in the average PTT values at each site were compared using the Kruskal-Wallis and Scheffé tests. P <.05 was considered to indicate statistical significance. The PTT was significantly greater at the superficial dorsal vein than at the basilic vein for all 3 noninvasive nerve conduction threshold frequencies (P < .05). The estimated PTT was significantly greater at the superficial dorsal vein than at the median cubital vein and cephalic vein at the carpus in response to 250-Hz stimulation (P < .05). The greater PTT of the superficial dorsal vein suggests that venipuncture at this site should result in the lowest pain intensity among all upper limb sites.