Measurement Of Thermal Thresholds Research Articles

Intravenous Magnesium Sulphate in Standing Horses: Effects on Physiological Parameters, Plasma Concentration of Magnesium and Nociceptive Threshold Tests☆

A bolus of 50 mg kg −1 MgSO4 (treatment Mg) or the same volume of saline (treatment S) was infused over 15 minutes in 5 adult healthy horses. T0 was the end of the infusion. Physiological parameters were recorded throughout the study period. Measurements of electrical, thermal, and mechanical nociceptive thresholds were performed at the pelvic limbs at baseline (before T0), and at specific timepoints. Blood samples were taken at fixed timepoints before, during and until 12 hours after the infusion. For statistical analysis, the 95% confidence intervals (CI's) for the differences in nociceptive thresholds between treatments were calculated. Physiological parameters were compared using a linear mixed model (global α = 0.05, with Bonferroni correction α = 0.0125). The concentrations of ions were also compared with the baseline values at specific timepoints, using a linear mixed model. The Pearson's correlation coefficient was derived between the ion concentrations. The 95% CI's of thermal, mechanical and electrical thresholds were [-1; +2]°C, [0; +3] N and [-1; +1] mA (positive differences indicate higher thresholds for treatment Mg), respectively. Heart rate was significantly higher (P < .0001) and non-invasive systolic arterial pressure (P < .0001) and respiratory rate (P = .0002) significantly lower after treatment Mg compared to treatment S. Additionally, non-invasive systolic arterial pressure was significantly different at T45 (P < .001). Although mild changes in cardiovascular parameters and plasma concentrations were seen with intravenous administration of MgSO4, no changes in nociceptive thresholds were detected in standing non-sedated horses.

Quantitative Sensory Testing in Children with Sickle Cell Disease

▪Background: Quantitative Sensory Testing (QST) is used in a variety of pain disorders such as arthritis and neuropathic pain syndromes, to characterize pain and predict prognosis and response to specific therapies. QST evaluates sensory function using a set of psychophysical procedures to measure subjective somatosensory responses to various physical stimuli. In Sickle Cell Disease (SCD) the painful vasoocclusive crisis is the most difficult management challenge and factors underlying the transition from acute to chronic pain and the wide interpatient variability in the pain experience are poorly understood. Optimal management for this complex pain syndrome remains unclear despite over three decades of basic and clinical research in the field.In this study, we aimed to duplicate results in the literature documenting altered QST thresholds in SCD and test the reproducibility of results over time to validate QST as a therapeutic endpoint for use in clinical trials evaluating novel preventative pain therapies.Objectives: Primary objectives were to test thermal thresholds in children with SCD versus African American controls and determine consistency over 6 months. Exploratory objectives were to correlate QST with clinical factors and select biomarkers and assess pressure pain thresholds (PPTs).Methods: Fifty-seven SCD and 60 control subjects aged 8-20 years underwent heat (wdt) and cold (cdt) detection and pain (hpt and cpt) threshold testing using a Medoc TSAII. A thermal composite score (TCS) was constructed by averaging the wdt, cdt, hpt, and cpt threshold responses from the testing instrument's starting temperature of 32°C. All participants were tested at baseline and 3 months; SCD subjects were additionally tested at 6 months and blood collected for future biomarker assessment. PPTs were performed using an SBMedic algometer. A single individual performed all QST. Descriptive statistics were computed and covariate-adjusted differences in thresholds within and between groups evaluated over time by mixed effects regression models with random intercepts and linear contrast tests. The intraclass correlation coefficient (ICC) from these models was used to assess within-subject consistency and Spearman's correlation was used to evaluate associations between thresholds and biomarkers. In addition, as a nested pseudo-intervention study, we analyzed a subset of “new” hydroxyurea (HU) users consisting of SCD subjects in whom HU was initiated within a few weeks prior to, or shortly after baseline testing. Significance was set at 0.05.Results: There were no significant differences in mean thermal or PPTs between SCD and control participants at baseline (Table 1) or month 3. QST measurements were consistent in SCD and control subjects for cpt, wdt, hpt and TCS (each ICC>0.55), but not necessarily for cdt (ICC = 0.37). Although generally internally consistent, there was some variability in mean thermal thresholds among SCD subjects over time, but the only significant difference between the 3 and 6 month means was for hpt (+0.67°C; 95% CI 1.15, 0.19). There was no association between mean thermal thresholds and chronic transfusion therapy. The group in whom HU was initiated shortly after baseline testing (n=6) demonstrated significant reductions in all thermal sensitivity and pain threshold measurements following HU initiation (Table 2).Conclusions: In contrast to Brandow's study (Brandow, American Journal Hematology, 2012), which documented thermal hypersensitivity in SCD, we have not demonstrated significant differences in thermal thresholds between SCD and control subjects. This could be due, in part, to differences in body sites used for testing. Results between second and third test sessions were highly consistent, indicating that reliability may improve once subjects have experience with QST. Subjects on whom HU was initiated shortly after baseline testing (new HU users) exhibited progressive and significant decreases in both cold and heat sensitivity from baseline to 6 months, suggesting that thermal testing is sensitive to effective therapy to prevent vasoocclusive pain. These findings are of critical importance to inform the planning of future SCD related clinical trials using QST as an endpoint in the evaluation of preventative pain therapies.Supported by National Institute of General Medical Sciences National Institutes of Health Award P20GM109021 and U54GM104941 [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Differing thermal sensitivities in a host–parasitoid interaction: High, fluctuating developmental temperatures produce dead wasps and giant caterpillars

Abstract Insect parasitoids, and the arthropod hosts they consume during development, are important ecological players in almost all environments across the globe. As ectothermic organisms, both parasitoid and host are strongly impacted by environmental temperature. If thermal tolerances differ between host insect and parasitoid, then the outcome of their interaction will be determined by the ambient temperature. As mean temperatures continue to rise and extreme temperatures become more frequent, we must determine the effect of high temperature stress on host–parasitoid systems to predict how they will fare in the face of climate change. The majority of studies conducted on host–parasitoid systems focus on either performance under constant temperature or a fixed metric of thermal tolerance (CTmax) for individual organisms. However, performance at constant temperatures is not predictive of performance under ecologically relevant, fluctuating temperatures and measurements of thermal thresholds provide little information regarding the effects of temperature throughout development. We address this by testing the effects of increasing mean temperature in both constant and fluctuating (±10°C) environments throughout development on the performance of the parasitoid wasp Cotesia congregata and its lepidopteran larval host, Manduca sexta. The growth of M. sexta was influenced by mean temperature, diurnal fluctuations and parasitization status. Caterpillar growth rate increased with increasing mean temperature, but decreased in response to diurnal fluctuations and parasitization by C. congregata wasps. Wasp survival decreased with increasing mean temperature and with diurnal fluctuations. The effect of diurnal fluctuations was stronger at higher mean temperatures. Diurnal fluctuations at our highest mean temperature treatment (30 ± 10°C) resulted in complete wasp mortality, and parasitized hosts displayed abnormal physiology, wherein they failed to exhibit wasp emergence, did not enter the prepupal stage, continued to feed and grew up to twofold larger than a normal, unparasitized caterpillar. Our results indicate hosts and parasitoids in this system have different thermal tolerances during development; the parasitoid wasp suffered complete mortality at a temperature regime that is mildly stressful for the unparasitized caterpillar host species. Our findings suggest C. congregata will suffer more severely under increasing temperatures than M. sexta, with cascading trophic and ecological effects. A free Plain Language Summary can be found within the Supporting Information of this article.

Somatosensory profiles in patients with non-specific neck-arm pain with and without positive neurodynamic tests

Despite normal neurological integrity tests, some patients with non-specific neck-arm pain (NSNAP) have heightened nerve mechanosensitivity upon neurodynamic testing. The aim of this study was to determine whether or not a nerve dysfunction is present in patients with positive neurodynamic tests compared to those with negative neurodynamic tests or healthy controls. Somatosensory profiling using quantitative sensory testing (QST) was established in 40 consecutive patients with unilateral NSNAP; 23 had positive upper limb neurodynamic tests (ULNTPOS) and 17 had negative neurodynamic tests (ULNTNEG) and in 26 healthy controls. QST included measurement of thermal and mechanical detection and pain thresholds in the maximal pain area on the symptomatic side as well as the corresponding contralateral area.Fifty-seven percent of patients with NSNAP had positive neurodynamic tests. Somatosensory profiling revealed a loss of function phenotype in NSNAP patients compared to healthy controls both in the maximal pain area and asymptomatic side. Hyperalgesia (cold, heat and pressure) was present bilaterally in both NSNAP groups. Direct comparison between the patient groups revealed no significant differences in somatosensory profiles. However, the ULNTPOS group demonstrated sensory loss compared to healthy controls in more parameters than the ULNTNEG group. The ULNTNEG subgroup represented an intermediate phenotype between ULNTPOS patients and healthy controls in most detection thresholds as well as thermal and pressure pain thresholds.Even though patients with NSNAP present as a spectrum, it remains unclear whether the sensory changes are indicative of a nerve dysfunction/lesion or rather a marker of altered central pain processing.

Pain and small-fiber affection in hereditary neuropathy with liability to pressure palsies (HNPP).

Background and aims Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal - dominant hereditary neuropathy caused by a deficiency in the peripheral protein PMP-22, due to deletion on chromosome 17p11,2 or in some rare cases point mutations in the PMP-22 gene. The clinical picture is characterized by recurrent mononeuropathies in nerves which frequently may be exposed to pressure, such as the median, ulnar, radial and peroneal nerves or also a more general neuropathy. Although pain is reported to be an unusual clinical symptom, there have been reports of pain in a surprisingly high proportion of these patients. Since pain may be explained by mechanisms in afferent small unmyelinated C- nerve fibers, an assessment of the function of small nerve fibers has been requested. The purpose of the present study was to investigate the presence of pain and the possible affection of afferent small nerve-fibers, A-δ and C-fibers, by quantitative sensory testing (QST)-assessment of thermal thresholds, as well as quantitative sudomotor axon reflex (QSART), a quantitative, validated assessment of efferent postganglionic sumodotor function. QST values were compared to values of age- and sex matched healthy subjects. Methods The 19 patients were investigated clinically, with an emphasis on pain characteristics, with nerve conduction studies (NCS) of major nerves in upper- and lower extremity, small fiber testing (QST, measurement of thermal thresholds) and with QSART. Results A total of 10 patients reported numbness in some extremity, suggesting entrapment of individual nerves as well as a general neuropathy, as verified by NCS in nine patients. A total of 15 patients had findings compatible with a general polyneuropathy. A total of eight patients reported pain, seven patients with pain in the feet, described as burning, aching, shooting and six with severe pathological QST values, mainly cold detection, but also four patients with elevated thresholds to warmth. Four of the patients had signs of a severe sensory neuropathy on NCS, with no sural findings. One patient had only pain in the arms, with only minor changes on NCS and with normal QST-values. Cold detection thresholds (CD) were significantly elevated (reduced sensibility) on the dorsum of the foot (mean of two feet), in patients [26.0 °C (19.7-28.0)] as compared with healthy subjects [28.6 °C (27.4-29.6) p = 0.000]. There were also significantly elevated warmth detection thresholds (WD) in feet in patients 39.5 °C (36.4-42.9) compared to healthy subjects [37.7 °C (36.1-39.4) p = 0.048]. However, there were no significant differences in QST values between patients with and without pain. Conclusions Of a total of 19 patients with verified HNPP, eight patients (42.1%) suffered from neuropathic pain, mainly in both feet. Implications Due to the high percentage of pain in HNPP, it is important not to disregard this diagnosis in a patient presenting with pain. Since there are no significant differences in QST values in patients with and without pain, routine QST studies in HNPP do not seem necessary.

A 4-year follow-up of non-freezing cold injury with cold allodynia and neuropathy in 26 naval soldiers.

Background and aims Non-freezing cold injuries (NFCI), which typically may occur in military personnel, may result from exposure to cold, at temperatures around 0 °C or above, and worsened by wind and moisture. The injury is due to cooling but not freezing of tissue like in frostbite. NFCI may result in in chronic neuropathy and cold hypersensitivity. A recent retrospective study of small-and large fibres has suggested that NFCI results in neuropathic pain due to a sensory neuropathy and question a longitudinal study to verify a possible observation of improvement of NFCI over time. The present study is a 4-year follow-up investigation of large - and small-fibre function in 26 naval cadets and officers who were exposed to cold injury during the same military expedition. Methods The 26 soldiers were investigated clinically (with investigation of motor function, reflexes, sensibility), with nerve conduction studies (NCS) of major nerves in upper- and lower extremity, small fibre testing (QST, measurement of thermal thresholds), measurements of subcutaneous fat tissue and maximal O2 uptake. Investigations found place 2 months following the actual military expedition, with follow-up investigations of affected soldiers at 6-12 months and up to 3-4 years. In order to elucidate possible mechanisms (disinhibition of cold pain by myelinated nerve fibres) of cold allodynia, cold pain thresholds were measured following an ischemic block of conduction of large and small myelinated nerve fibres. Results Of 26 soldiers, 19 complained of numbness in feet and a large majority of 16 of cold hypersensitivity 2 months following injury. There were significant alterations of both large- and small-fibre function, indicating a general large- and small-fibre neuropathy. The most prominent finding was a pronounced cold allodynia, inversely correlated with the amount of subcutaneous fat. During the first year, results of NCS and thermal testing gradually normalized in most. Seven soldiers developed chronic symptoms in the form of cold hypersensitivity and with findings of cold allodynia, which was not further enhanced, but abolished following block of conduction of myelinated nerve fibres. Seven soldiers were free of symptoms from that start of the investigation, probably because they had been more eager to keep their legs moving during the exposure to cold. Conclusions Of a total of 26 soldiers, only seven developed chronic symptoms of cold hypersensitivity, corresponding to the finding of cold allodynia by thermal testing. The cold allodynia may not be explained by disinhibition of cold pain by myelinated fibres as in healthy subjects. A large majority recovered from an initial large-and small fibre neuropathy, demonstrating that recovery from NFCI may occur. Implications Although large-and small fibre neuropathy may be restored following cold injury, there is a risk of a permanent and disabling cold hypersensitivity, corresponding to the findings of cold allodynia. It is of uttermost importance to secure military personnel from the risk of cold injuries. It seems important to avoid immobilisation of extremities during exposure to cold.

Nanoscale Wetting and Energy Transmission at Solid/Liquid Interfaces.

Understanding the effects and limitations of solid/liquid interfaces on energy transport is crucial to applications ranging from nanoscale thermal engineering to chemical synthesis. Until now, the majority of experimental evidence regarding solid/liquid interactions has been limited to macroscale observations and experiments. The lack of experimental works exploring nanoscale solid/liquid interactions has been accentuated as the body of knowledge from theory and simulations at these scales has exploded in recent years. In this study, we expand on current nanoscale thermal measurement techniques in order to more fully understand solid/liquid interfacial energy transport. We use thermal ablation threshold measurements on thick Au films in various liquids as a metric to describe thermal transport at the Au/liquid interface. Furthermore, using ultrafast pump-probe experiments, we gain insight into this transport through picosecond ultrasonic coupling at solid/liquid interfaces with known macroscopic observations. We find significant variations in both the ablation threshold and the damping of the acoustic modes within the Au films depending on nanoscopic interactions at the solid/liquid interface rather than typical macroscale metrics such as acoustic mismatch, measured contact angle, and work of adhesion.

Thermal perception thresholds among workers in a cold climate

PurposeTo investigate whether exposure to cold could influence the thermal perception thresholds in a working population.MethodsThis cross-sectional study was comprised of 251 males and females and was carried out at two mines in the northern part of Norway and Sweden. The testing included a baseline questionnaire, a clinical examination and measurements of thermal perception thresholds, on both hands, the index (Digit 2) and little (Digit 5) fingers, for heat and cold.ResultsThe thermal perception thresholds were affected by age, gender and test site. The thresholds were impaired by experiences of frostbite in the fingers and the use of medication that potentially could affect neurosensory functions. No differences were found between the calculated normative values for these workers and those in other comparative investigations conducted in warmer climates.ConclusionsThe study provided no support for the hypothesis that living and working in cold climate will lead to impaired thermal perception thresholds. Exposure to cold that had caused localized damage in the form of frostbite was shown to lead to impaired thermal perception.

Assessment of a carbon dioxide laser for the measurement of thermal nociceptive thresholds following intramuscular administration of analgesic drugs in pain-free female cats

ObjectiveTo assess the potential of a thermal carbon dioxide (CO2) laser to explore antinociception in pain-free cats. Study designExperimental, prospective, blinded, randomized study. AnimalsSixty healthy adult female cats with a (mean ± standard deviation) weight of 3.3 ± 0.6 kg. MethodsCats were systematically allocated to one of six treatments: saline 0.2 mL per cat; morphine 0.5 mg kg−1; buprenorphine 20 μg kg−1; medetomidine 2 μg kg−1; tramadol 2 mg kg−1, and ketoprofen 2 mg kg−1. Latency to respond to thermal stimulation was assessed at baseline and at intervals of 15–30, 30–45, 45–60, 60–75, 90–105 and 120–135 minutes. Thermal thresholds were assessed using time to respond behaviourally to stimulation with a 500 mW CO2 laser. Within-treatment differences in response latency were assessed using Friedman’s test. Differences amongst treatments were assessed using independent Kruskal–Wallis tests. Where significant effects were identified, pairwise comparisons were conducted to elucidate the direction of the effect. ResultsCats treated with morphine (X2 = 12.90, df = 6, p = 0.045) and tramadol (X2 = 20.28, df = 6, p = 0.002) showed significant increases in latency to respond. However, subsequent pairwise comparisons indicated that differences in latencies at specific time-points were significant (p < 0.05) only for tramadol at 60–75 and 90–105 minutes after administration (21.9 and 43.6 seconds, respectively) in comparison with baseline (11.0 seconds). No significant pairwise comparisons were found within the morphine treatment. Injections of saline, ketoprofen, medetomidine or buprenorphine showed no significant effect on latency to respond. Conclusions and clinical relevanceThe CO2 laser technique may have utility in the assessment of thermal nociceptive thresholds in pain-free cats after analgesic administration and may provide a simpler alternative to existing systems. Further exploration is required to examine its sensitivity and comparative utility.

Complex regional pain syndrome following viper-bite

BackgroundComplex regional pain syndrome (CRPS) may occur following fractures, surgery or different trauma. Development of CRPS following snake-bite has only been published in three reports (from Turkey, Nepal and Korea), although snake bites occur frequently world-wide. There has been no report from Western Europe. Vipera Berus is a common snake in European countries and the only venomous snake in Norway. We here describe the development of CRPS in a young woman as a consequence of a viper bite (Vipera Berus) in the right arm. MethodsWe performed a clinical investigation (inspection, measurement of skin temperatures, sensory and motor evaluation) of the patient six months following the viper-bite, measurement of thermal thresholds (quantitative sensory testing, QST), measurement of resting sweat output (RSO) and quantitative sudomotor axon reflex (QSART) from both arms. ResultsThe patient fulfilled the Budapest criteria for a CRPS-condition, with continuous pain and symptoms and findings of autonomic dysfunction. In addition, we found elevated thresholds of warmth and cold, evidence of an affection of afferent A-delta and C-fibres as well as an affection of the efferent sympathetic sudomotor C-fibres by QSART. An increased RSO-volume was in inverse relationship to the decreased QSART result. Conclusion and ImplicationsIt is important to be aware of viper-bite as a possible eliciting event for CRPS for early diagnosis and treatment of a patient. As long-lasting pain and oedema are known complications, it is probable that CRPS after viper-bites previously may have been underdiagnosed. As many patients are unaware of being bit, viper bite should be considered in cases of unexplained sudden pain and swelling of a limb.

Changes of voltage-gated sodium channels in sensory nerve regeneration and neuropathic pain models.

The present study was conducted to determine changes in the expression of voltage-gated sodium channels (VGSCs) α-subunits after nerve injury and their relation with development of neuropathic pain. We used the crush injury model of regeneration of the sciatic nerve (Crush) and the spared nerve injury (SNI) model of neuropathic pain in the rat. Measurements of thermal and mechanical pain thresholds were performed until 3 months after injury. Real-time PCR and immunohistochemistry of VGSC α-subunits were used to evaluate the mRNA and protein expression in the DRG. Both nerve injuries induced similar alterations in the VGSCs expression at 7 dpi, with upregulation of Nav1.3, and downregulation of Nav1.7, Nav1.8 and Nav1.9. These changes persisted until 28 days, when hyperalgesia was still present in SNI but not in Crush rats. At 90 days, mRNA expression of all analyzed α-subunits returned to basal levels in the Crush group. However, SNI rats still showed altered expression of VGSCs, and neuropathic pain responses. Immunohistochemical staining revealed that Nav1.8 and Nav1.9 were widely expressed in IB4-positive neurons of the DRG, relevant in pain processing. The population of neurons coexpressing each α-subunit and IB4 was also affected by the injury, more markedly after the Crush. Shifts in VGSCs expression occur in parallel to neuropathic pain behavior in rats early after injury, while at later times they appear to be more related to sensory nerve degeneration and regeneration processes.

No Evidence for the Development of Acute Analgesic Tolerance during and Hyperalgesia after Prolonged Remifentanil Administration in Mice

BackgroundAcute opioid tolerance (AOT) and opioid-induced hyperalgesia (OIH) are undesirable effects of opioids that have been reported in both animals and humans. However, the development of AOT and OIH in cases of potent, short-acting μ-opioid receptor agonist remifentanil administration remains controversial. It has been suggested that the emergence of AOT and OIH by remifentanil could be dose and infusion duration dependent, i.e., low dose and short infusions may lead to negative results. In this study, we determined whether AOT and OIH could be elicited by prolonged, continuous administration of remifentanil at maximally tolerable doses in C57BL/6 mice.ResultsThe analgesic effects of continuously administered remifentanil [by short (1 h) and prolonged (4 h) intraperitoneal infusions] were studied. These experiments involved repeated measurements of thermal thresholds during remifentanil administration. Therefore, particular attention was paid to prevent cumulative tissue injury, which could mimic pronociceptive effects of remifentanil. To exclude the possibility of pseudoAOT during infusion, we used brief cooling of all ipsilateral hindpaws that exhibited analgesic response. Thermal thresholds remained steadily elevated over a 1-h period during continuous administration at infusion rates of 120, 180, and 240 mg/kg/h, which indicated no AOT development. To exclude the possibility of pseudoOIH after infusion, intact contralateral hindpaws were used for all postinfusion threshold measurements. Thermal thresholds at each infusion rate returned to the baseline values within 15 min after the termination of the administration. They did not decrease below the baseline values during 1 h following infusion, which indicated no OIH development. Similar threshold dynamics were also observed for thermal and mechanical testing modalities in animals infused at 120 mg/kg/h for 4 h as well as in animals with rapidly attained and maintained maximum analgesia for 3 h.ConclusionsThese results suggest that neither intra-infusion AOT nor postinfusion OIH develops in mice receiving continuous remifentanil when the possibility of cumulative tissue injury mimicking AOT or OIH is carefully avoided.

Combined testing of autonomic and sensory dysfunction in patients with unilateral facial flushing and sweating during exercise

Patients with unilateral facial flushing are occasionally referred to clinical neurophysiological evaluation with the question of the site of lesion. These patients may have a mixture of autonomic and sensory symptoms. We wanted to study to which extent a combined autonomic and sensory clinical neurophysiological testing before and after exercise may help in the diagnostic evaluation of the patients. Five patients were investigated at rest with quantitative sensory thresholds (QST, measurement of thermal thresholds) and quantitative sudomotor axon reflex test (QSART) in all extremities. Sweet volumes (QSWEAT) and skin temperatures were then measured after 30 to 60 minutes of exercise. Marked side-to-side differences were observed for QST and QSART at rest as well as for QSWEAT and skin temperatures following exercise, in accordance with the patients' symptoms. However, asymptomatic abnormal findings were also demonstrated in the feet of four patients, following both crossed and non-crossed distributions. EMG/neurography and MRI-findings were normal in all patients and no aetiological explanations were found. Combined autonomic and sensory testing including the legs provided evidence of unexpectedly more widespread abnormalities, including asymptomatic findings. Although the patients presented with seemingly similar symptoms, there was a striking heterogeneity in their results, suggesting different sites of dysfunction. An extracranial lesion was considered likely in one or maybe two patients, while the possibility of a central lesion had to be considered in the three other patients.

Neurophysiological Testing to Assess Penile Sensory Nerve Damage After Radical Prostatectomy

Radical prostatectomy (RP) can lead to erectile dysfunction due to surgical injury of the cavernous nerves. However, there is no simple, objective test to evaluate cavernous nerve damage caused by RP in clinical practice. To assess the value of the measurement of penile thermal and vibratory sensory thresholds to reflect cavernous nerve damage caused by RP. We included 42 consecutive patients who underwent RP with cavernous nerve sparing (laparoscopic approach, N = 12) or without cavernous nerve sparing (laparoscopic, N = 13; retropubic, N = 11; or transperineal, N = 6). Penile thermal (warm and cold) and vibratory sensory thresholds were measured twice, together with the Erectile Dysfunction Symptom Score (EDSS), 1 month before and 2 months after RP. Penile sensory thresholds for warm, cold, and vibration sensations. Penile sensory thresholds for warm (P < 0.0001) and cold (P < 0.0001) sensations significantly increased after non-nerve-sparing RP, but not after nerve-sparing RP. Vibration threshold only increased after transperineal non-nerve-sparing RP (P = 0.031). EDSS values were significantly increased in all groups of patients 2 months after surgery. Sensory nerve fibers carrying penile skin sensations travel with the cavernous nerves in the pelvis. Therefore, testing these sensations may help to evaluate the extent of cavernous nerve damage caused by RP. In this series, post-operative changes in penile sensory thresholds differed with the surgical technique of RP, as the cavernous nerves were preserved or not. The present results support the value of quantitative penile sensory threshold measurement to indicate RP-induced cavernous nerve injury.

Comparison of the analgesic efficacy of oral ABT-116 administration with that of transmucosal buprenorphine administration in dogs

To evaluate the analgesic efficacy of ABT-116, a transient receptor potential cation channel vanilloid subfamily V member 1 antagonist, and compare it with that of buprenorphine by measurement of mechanical and thermal nociceptive thresholds in dogs. Six 7- to 8-month-old dogs (3 males and 3 females). In a crossover study design, all dogs received ABT-116 (30 mg/kg, PO) and buprenorphine (0.03 mg/kg, orotransmucosally), with each treatment separated by 1 week. Physiologic variables were recorded prior to and 1, 6, and 24 hours after drug administration. Thermal (thoracic) and mechanical (dorsolateral aspect of the radius [proximal] and dorsopalmar aspect of the forefoot [distal]) nociceptive thresholds were assessed prior to (baseline) and 15 minutes and 1, 2, 4, 6, 12, 18, and 24 hours after treatment. Buprenorphine administration resulted in higher overall thermal and proximal mechanical nociceptive thresholds, compared with ABT-116. Distal mechanical nociceptive thresholds after treatment were higher than baseline values for both treatments, but the magnitude of change was greater for buprenorphine at 1 hour after administration. Whereas HR and RR sporadically differed from baseline values after ABT-116 administration, rectal temperature increased from a baseline value of 39 ± 0.2°C (mean ± SD) to a peak of 40.6 ± 0.2°C at 6 hours. In dogs without inflammation or nerve injury, PO administration of ABT-116 did not consistently result in an increase in nociceptive thresholds. However, clinically relevant increases in rectal temperature were identified after ABT-116 administration.

Antinociceptive effects of nalbuphine hydrochloride in Hispaniolan Amazon parrots (Amazona ventralis)

To evaluate the antinociceptive effects and duration of action of nalbuphine HCl administered IM on thermal thresholds in Hispaniolan Amazon parrots (Amazona ventralis). 14 healthy adult Hispaniolan Amazon parrots of unknown sex. 3 doses of nalbuphine (12.5, 25, and 50 mg/kg, IM) and saline (0.9% NaCl) solution (control treatment) were evaluated in a blinded complete crossover experimental design by use of foot withdrawal threshold to a noxious thermal stimulus. Baseline data on thermal threshold were generated 1 hour before administration of nalbuphine or saline solution; thermal threshold measurements were obtained 0.5, 1.5, 3, and 6 hours after administration. Nalbuphine administered IM at 12.5 mg/kg significantly increased the thermal threshold (mean change, 2.4°C), compared with results for the control treatment, and significantly changed thermal threshold for up to 3 hours, compared with baseline results (mean change, 2.6° to 3.8°C). Higher doses of nalbuphine did not significantly change thermal thresholds, compared with results for the control treatment, but had a significant effect, compared with baseline results, for up to 3 and 1.5 hours after administration, respectively. Nalbuphine administered IM at 12.5 mg/kg significantly increased the foot withdrawal threshold to a thermal noxious stimulus in Hispaniolan Amazon parrots. Higher doses of nalbuphine did not result in significantly increased thermal thresholds or a longer duration of action and would be expected to result in less analgesic effect than lower doses. Further studies are needed to fully evaluate the analgesic effects of nalbuphine in psittacine species.

Longitudinal study of wind-up responses after graded spinal cord injuries in the adult rat

The main objectives of this work were to evaluate the development of neuropathic pain after spinal cord injuries of different severities, and to assess changes in central excitability and plasticity by means of wind-up responses and withdrawal reflexes. Two groups of rats were subjected to spinal cord contusion with forces of 100 or 200 kdyn applied at T8. Measurements of thermal and mechanical pain thresholds as well as wind-up measurements were performed weekly during two months after injury. Withdrawal reflexes were also assessed electrophysiologically. We found that animals with contusion of different severities showed a similar reduction in nociceptive thresholds. All contused animals showed increased wind-up responses compared to intact animals during the first 2 to 6 weeks post injury. The mean increase of wind-up was higher in rats with stronger spinal cord contusion. Results from the withdrawal reflexes did not correlate with nociceptive behaviors nor wind-up responses, highlighting the plasticity of spinal circuits modulation after SCI. These results indicate that the graded-force spinal cord contusion model is suitable for studying central neuropathic pain, and for assessing changes in wind-up responses. Wind-up measurements can be used as a non-invasive technique to detect changes in central excitability after SCI of different severities.

Quantitative somatosensory testing of subjects with chronic post-traumatic headache: Implications on its mechanisms

Background Chronic headache is one of the most prominent symptoms among subjects with traumatic head injury (THI) . Despite the relatively high prevalence of chronic post-traumatic headache (CPTHA) and its enormous effect on the already poor quality of life of subjects with THI, its mechanisms has not been studied in depth. Objective To conducted quantitative somatosensory testing in THI subjects with and without chronic post-traumatic headache (CPTHA) in order to shed light on the yet, unknown pathophysiology of CPTHA. Methods THI subjects with and without CPTHA and healthy controls underwent thermal and mechanical threshold measurements in painful and pain-free regions in the head and in their hands (a remote pain-free region) and filled out and the post-traumatic stress disorder (PTSD) inventory. In addition, the THI and CPTHA filled out the Mc’Gill pain questionnaire (MPQ). Results THI subjects with CPTHA had significantly higher thermal thresholds in both the head and hand indicating central damage to the pain and temperature system and in addition, a significantly lower pressure-pain threshold in the head as well as more severe PTSD symptomatology than the pain-free THI subjects and healthy controls. Conclusions The sensory profile of subjects with CPTHA suggests that CPTHA may be a form of central pain. The cranial mechanical hyperalgesia may originate from peripheral tissue damage accompanying the THI. Psychological factors may contribute to the development, and maintenance of CPTHA in susceptible individuals.

Influence of intrinsic noise generated by a thermotesting device on thermal sensory detection and thermal pain detection thresholds

Various factors can influence thermal perception threshold measurements and contribute significantly to unwanted variability of the tests. To minimize this variability, testing should be performed under strictly controlled conditions. Identifying the factors that increase the variability and eliminating their influence should increase reliability and reproducibility. Currently available thermotesting devices use a water-cooling system that generates a continuous noise of approximately 60 dB. In order to analyze whether this noise could influence the thermal threshold measurements we compared the thresholds obtained with a silent thermotesting device to those obtained with a commercially available device. The subjects were tested with one randomly chosen device on 1 day and with the other device 7 days later. At each session, heat, heat pain, cold, and cold pain thresholds were determined with three measurements. Bland-Altman analysis was used to assess agreement in measurements obtained with different devices and it was shown that the intersubject variability of the thresholds obtained with the two devices was comparable for all four thresholds tested. In contrast, the intrasubject variability of the thresholds for heat, heat pain, and cold pain detection was significantly lower with the silent device. Our results show that thermal sensory thresholds measured with the two devices are comparable. However, our data suggest that, for studies with repeated measurements on the same subjects, a silent thermotesting device may allow detection of smaller differences in the treatment effects and/or may permit the use of a smaller number of tested subjects. Muscle Nerve 40: 257-263, 2009.

Effect of thermode application pressure on thermal threshold detection

Studies using quantitative sensory testing (QST) often present incongruent results due to intra- and intersubject as well as interobserver variability which limit widespread use of the technique. Eliminating or reducing the factors responsible for this variability is of great interest, as it increases reliability and reproducibility of QST. Thermal sensory threshold determination is a crucial part of QST. It was previously suggested that the pressure of the thermode on the skin could influence measurements. To verify this, we developed a new thermode with a built-in pressure sensor. Thresholds obtained with this thermode were compared to those obtained with a commercially available thermotesting device (Medoc TSA-II). Heat detection and heat pain detection thresholds were higher, and cold detection thresholds were lower when measured with our thermode than they were with the Medoc thermode. Cold pain detection thresholds did not differ between the thermodes. Analysis of the heat transfer capacity of the thermodes indicated that the material of the skin contact surface of the thermode may play a role in these shifts in threshold values. Altering the thermode pressure on the skin did not affect the thermal thresholds. Furthermore, the intrasubject variability of the measurements (minimal-to-maximal range of measured threshold values in individual subjects) was also not influenced by the pressure with which the thermode was attached to the skin. Our results suggest that the pressure with which the thermode is attached to the skin does not significantly affect the intra- and intersubject reproducibility of the thermal sensory threshold measurements.