Sensory correlates of pain in peripheral neuropathies

ObjectiveTo characterize sensory threshold alterations in peripheral neuropathies and the relationship between these alterations and the presence of pain.MethodsSeventy-four patients with length-dependent sensory axonal neuropathy were enrolled, including 38 patients with painful neuropathy (complaining of chronic, spontaneous neuropathic pain in the feet) and 36 patients with painless neuropathy. They were compared to 28 age-matched normal controls. A standardized quantitative sensory testing protocol was performed in all individuals to assess large and small fiber function at the foot. Large fibers were assessed by measuring mechanical (pressure and vibration) detection thresholds and small fibers by measuring pain and thermal detection thresholds.ResultsBetween patients with neuropathy and controls, significant differences were found for mechanical and thermal detection thresholds but not for pain thresholds. Patients with painful neuropathy and those with painless neuropathy did not differ regarding mechanical or thermal thresholds, but only by a higher incidence of thermal or dynamic mechanical allodynia in case of painful neuropathy. Pain intensity correlated with the alteration of thermal detection and mechanical pain thresholds.ConclusionsQuantitative sensory testing can support the diagnosis of sensory neuropathy when considering detection threshold measurement. Thermal threshold deterioration was not associated with the occurrence of pain but with its intensity.SignificanceThere is a complex relationship between the loss or functional deficit of large and especially small sensory nerve fibers and the development of pain in peripheral neuropathy.     

Psychophysical detection and pain ratings of incremental thermal stimuli: A comparison with nociceptor responses in humans

The capacity of humans to detect and scale the magnitude of pain elicited by small increments in temperature, delivered by a contact thermal stimulator to localized areas of the arm or leg, was measured on non-painful and painful adaption temperatures. Subjects continuously rated the magnitude of any pain sensation elicited by heat increments superimposed on base temperatures of 38, 44, 47 or 48 °C. Detection threshold was also measured using a two-alternative forced choice method. The increment detection thresholds were lower for a continuously painful base of 47 °C than for a non-painful base of 38 °C in normal skin, and likewise were lower for a base of 38 °C following hyperalgesia induced by a mild burn. Incremental pain thresholds were nearly equal to detection thresholds on the base of 47 °C. The sensitivity with which subjects could scale the magnitude of pain was 2–7 times better for increments delivered on a 48 °C as opposed to a 38 °C base.Evoked responses in 6 single C-fiber mechanoheat nociceptive afferents (CMHs) were recorded percutaneously from the peroneal nerves of 3 humans, who were simultaneously judging pain magnitude. For a base of 38 °C, both the pain and the neural response thresholds were an order of magnitude higher than corresponding thresholds on a base of 48 °C. For a base of 47 °C, response thresholds of the CMHs ranged from 0.1 to 0.5 °C and were comparable to detection thresholds of 0.1 to 0.3 °C. The sensitivity with which most nociceptors could signal increment size was 3–4 times better on a 48 °C than a 38 °C base.Incremental pain sensitivity was not altered by a compression block of activity in myelinated afferents that eliminated the sense of cool and touch. Thus, activity in unmyelinated fibers alone could account for the sensitivity to incremental thermal stimuli that were superimposed on a painful base temperature. Further, it is likely that CMH nociceptors alone could provide the peripheral information necessary to detect and to make magnitude judgments of pain elicited by these stimuli.     

Study of pain thresholds by recording flexor reflexes in thalamic syndromes

Both thresholds of nociceptive flexion reflex and pain sensation were studied in 6 normal subjects and in 6 patients with typical thalamic pain. In these patients, on the painful side, these thresholds were found increased (98 p. 100; 89 p. 100 respectively) compared to the normal side. Values obtained in this latter did not significantly differ from those observed in normal subjects. After 8 days of indalpine treatment, the nociceptive reflex threshold was furthered increased in the painful side while the pain threshold was not modified by this drug. In the normal side, changes observed after indalpine were similar to that obtained in normal subjects. All the indalpine-induced modifications were reversed by naloxone in both patients and normals. These results are discussed in the context of the possible mechanisms of thalamic hyperpathia.     

Somatosensory findings in patients with spinal cord injury and central dysaesthesia pain.

OBJECTIVE: To determine whether central pain in patients with spinal cord injury is only dependent on the lesioning of spinothalamic pathways. METHODS: In sixteen patients with spinal cord injury and central dysaesthesia pain, somatosensory abnormalities in painful denervated skin areas were compared with somatosensory findings in normal skin areas as well as in non-painful denervated skin areas. RESULTS: The threshold values for detection of thermal (heat, cold, heat pain, or cold pain) and tactile stimulation were significantly changed in denervated skin areas although there were no significant differences in the threshold values between painful and non-painful denervated skin areas. The reductions of sensations of touch, vibration, joint position, and two point discrimination in painful and non-painful denervated skin areas were not significantly different. Allodynia (pain caused by non-noxious stimulation) and wind up-like pain (pain caused by repeatedly pricking the skin) were significantly more common in painful than non-painful denervated skin areas. CONCLUSIONS: Because pain and thermal sensory perception are primarily mediated to the brain via spinothalamic pathways, whereas the sensations of touch, vibration and joint position are primarily mediated by dorsal column-medial lemniscal pathways, the results indicate that central pain is not only dependent on the lesioning of either dorsal column-medial lemniscal pathways or spinothalamic pathways. The findings of abnormal evoked pain (allodynia and wind up-like pain) may be consistent with the experimental findings of hyperexcitability in nociceptive spinothalamic tract neurons, that may be involved in the pathogenesis of central pain.     

Diabetic painful and insensate neuropathy: Pathogenesis and potential treatments

Advanced peripheral diabetic neuropathy (PDN) is associated with elevated vibration and thermal perception thresholds that progress to sensory loss and degeneration of all fiber types in peripheral nerve. A considerable proportion of diabetic patients also describe abnormal sensations such as paresthesias, allodynia, hyperalgesia, and spontaneous pain. One or several manifestations of abnormal sensation and pain are described in all the diabetic rat and mouse models studied so far (i.e., streptozotocin-diabetic rats and mice, type 1 insulinopenic BB/Wor and type 2 hyperinsulinemic diabetic BBZDR/Wor rats, Zucker diabetic fatty rats, and nonobese diabetic, Akita, leptin- and leptin-receptor-deficient, and high-fat diet—fed mice). Such manifestations are 1) thermal hyperalgesia, an equivalent of a clinical phenomenon described in early PDN; 2) thermal hypoalgesia, typically present in advanced PDN; 3) mechanical hyperalgesia, an equivalent of pain on pressure in early PDN; 4) mechanical hypoalgesia, an equivalent to the loss of sensitivity to mechanical noxious stimuli in advanced PDN; 5) tactile allodynia, a painful perception of a light touch; and 5) formalin-induced hyperalgesia. Rats with short-term diabetes develop painful neuropathy, whereas those with longer-term diabetes and diabetic mice typically display manifestations of both painful and insensate neuropathy, or insensate neuropathy only. Animal studies using pharmacological and genetic approaches revealed important roles of increased aldose reductase, protein kinase C, and poly(ADP-ribose) polymerase activities, advanced glycation end-products and their receptors, oxidative-nitrosative stress, growth factor imbalances, and C-peptide deficiency in both painful and insensate neuropathy. This review describes recent achievements in studying the pathogenesis of diabetic neuropathic pain and sensory disorders in diabetic animal models and developing potential pathogenetic treatments.     

Neonatal ventral hippocampal lesions modify pain perception and evoked potentials in rats

This work concerns the debate surrounding the modified pain reactivity of patients with schizophrenia and other possible perceptive distortions. Rats with a neonatal ventral hippocampal lesion (NVHL) were used to model the neuro-developmental aspect of schizophrenia, and their reactivity to various stimuli was evaluated. The results could also help understand sensory deficits in other neuro-developmental disorders. Behavioural reactions to graduated painful thermal and mechanical stimuli were observed, and evoked potential responsiveness to tactile, visual and acoustic non-painful stimuli was recorded and compared to non-operated and sham lesioned controls. A higher threshold was observed with painful mechanical stimuli and shorter paw withdrawal latency with thermal stimuli. This was particularly relevant as there was no change in the evoked potentials triggered by non-nociceptive tactile stimulation of the same part of the body. There was a 10dB(A) increase in the auditory threshold and a suppression of auditory sensory motor gating. Visually evoked potentials did not appear to be affected. Taken together, the results showed that NVHL-evoked alteration of brain development induces mechanical hypoalgesia, thermal hyperalgesia and auditory sensory changes. The data also contribute towards elucidating mechanisms underlying sensory deficits in neurodevelopmental diseases, including schizophrenia.     

Correlation and cluster analysis of sensory, pain, and reflex thresholds to various stimulus modalities in symptom-free subjects.

OBJECTIVE: In order to evaluate the possible relation between the psychophysical response and a motor reflex, sensory and pain thresholds to various stimuli were analyzed in combination with the occurrence threshold of the late masseteric exteroceptive suppression (ES2) period. METHODS: Twenty men and 20 women participated. The tactile detection threshold and the filament-prick pain detection threshold were measured on the cheek skin overlying the left masseter muscles. The pressure pain threshold and pressure pain tolerance threshold were measured at the left masseter muscle. The surface EMG was recorded from the left masseter muscle, while electrical stimuli with 13 fixed intensities were applied to the skin above the left mental nerve. The stimulation intensity at which the ES2 appeared for the first time and the lowest stimulus intensity at which the subjects reported to be painful were defined as the ES2 and pain threshold, respectively. RESULTS: There were significant positive correlations between the tactile detection threshold and the pain thresholds determined using the different stimulus modalities, and the ES2 threshold was also significantly correlated with the pain thresholds (P<0.05). Cluster analysis could significantly discriminate two distinct groups with high versus low tactile, pain and ES2 thresholds (P<0.05). CONCLUSIONS: The present findings suggested that the ES2 reflex response has a relation with the individual sensory and pain sensitivity in symptom-free subjects. SIGNIFICANCE: Combined examination of sensory, pain, and ES2 thresholds might provide complementary information on the pathophysiology underlying orofacial pain.     

Increased prefrontal activation during pain perception in major depression.

BACKGROUND: To further elucidate the close interrelation of pain and depression, we investigated cerebral responses to parametrically varied thermal pain intensities in female patients suffering from major depressive disorder (MDD) (n = 13) and matched control subjects (n = 13) by means of functional magnetic resonance imaging (fMRI). METHODS: After the assessment of the individual thermal pain threshold, an fMRI-compatible thermode was used to deliver thermal painful stimuli to the right arm. All stimuli were initiated for 10 sec from a baseline resting temperature (32 degrees C) in three different conditions (37 degrees C, 42 degrees C, 45 degrees C). Statistical Parametric Mapping 2 (SPM2) software was used for image processing and statistical analyses. RESULTS: Patients displayed significantly increased thermal pain thresholds. A comparable increase in blood oxygenation level-dependent (BOLD) signal was observed in key structures of the pain matrix in patients and control subjects. Patients displayed hyperactivation in comparison with control subjects for the painful 45 degrees C condition in the left ventrolateral thalamus, in the right ventrolateral prefrontal cortex (VLPFC) and dorsolateral prefrontal cortex (DLPFC), as well as a stronger parametric BOLD signal increase in the right VLPFC, DLPFC, and in the contralateral insula. Symptom severity correlated positively with the BOLD signal in the left ventrolateral nucleus of the thalamus. CONCLUSIONS: We present evidence that cortical structures of the pain matrix are similarly activated in depressed patients and healthy subjects. We report increased prefrontal and lateral thalamic activation during the presentation of painful stimuli, which might explain reduced thermal pain perception on the skin in depressed patients.     

Experimental changes in pain threshold and severe pain threshold for electrically induced pain

Pain and severe pain thresholds were measured in groups of 15 (Experiment 1) and 20 (Experiment 2) normal volunteers. In Experiment 1, the subjects underwent a series of ten constant level, painful stimuli each of 10 sec duration at an arbitrarily chosen level between the thresholds. This level was recorded. It ranged from 14% to 81% of the difference between thresholds. The thresholds were then remeasured. For the second experiment the experimental stimulus commenced at a non-painful level and increased over a period of 5 sec to a level midway between thresholds for a series of three stimuli and again thresholds were remeasured. An overall effect was demonstrable only in Experiment 2, where the severe pain threshold was significantly reduced (p less than 0.001). There was a marked individual variation with increases and decreases in both thresholds occurring in different individuals at significance levels varying from p less than 0.05 to p less than 0.001. No subject changed the two thresholds in opposite directions. Examination of the responses in Experiment 1 suggested that for any increase in either threshold to occur it was necessary that the repeated painful stimulus should be at a level below the mid-point between the two thresholds, but that this was not a sufficient condition.     

Effect of levodopa on pain threshold in Parkinson's disease: a clinical and positron emission tomography study.

Patients suffering from Parkinson's disease (PD) frequently experienced painful sensations that could be in part due to central modification of nociception. We compared pain threshold before and after administration of levodopa in PD patients and in controls, and investigated cerebral activity with positron emission tomography (PET) during experimental nociceptive stimulation. Pain threshold was determined using thermal stimulation during two randomized conditions: off and on. We performed H(2) (15)O PET analysis of regional cerebral blood flow on subjects while they received alternate randomized noxious and innocuous stimuli during off and on conditions. In off condition, pain threshold in nine PD patients was significantly lower than in nine controls. Administration of levodopa significantly raised pain threshold in PD patients but not in controls. During off condition, there was a significant increase in pain-induced activation in right insula and prefrontal and left anterior cingulate cortices in PD compared to control group. Levodopa significantly reduced pain-induced activation in these areas in PD. This study shows that pain threshold is lower in PD patients but returns to normal ranges after levodopa administration. Moreover, PD patients have higher pain-induced activation in nociceptive pathways, which can be reduced by levodopa.     

Responses of neurons in the region of human thalamic principal somatic sensory nucleus to mechanical and thermal stimuli graded into the painful range.

The role of the region of the principal somatic sensory nucleus of the human thalamus (ventral caudal - Vc) in signaling painful sensations is unclear. We have now studied the response of cells (n = 57) in this region to both thermal and mechanical stimuli graded into the painful range during surgeries (n = 24) for treatment of movement disorders. Fifteen cells had a graded response to mechanical stimuli extending into the painful range and, thus, were classified in the wide dynamic range (WDR) category. The mean stimulus-response function of cells in the WDR class, normalized to baseline, showed a fourfold mean increase in firing rate above baseline across the mechanical series of stimuli. Seven of these cells responded to heat stimuli (WDR-H) and two responded to cold stimuli (WDR-C). Twenty-five cells were in a class (multiple receptive - MR) that showed a response to both brush and compressive stimuli, although the responses were not graded into the painful range. Three of these cells (MR-H) had a response to heat stimuli and five cells responded to cold stimuli (MR-C). Nine cells responded to brushing without a response to the compressive stimuli (low threshold - LT). Cells responsive to painful mechanical and thermal stimuli were located throughout the thalamic region where cells responded to nonpainful cutaneous stimulation. These results show that cells in the region of the human thalamic principal somatic sensory nucleus respond to mechanical and thermal stimuli extending into the painful range.     

Intrathecal administration of an NMDA or a non-NMDA receptor antagonist reduces mechanical but not thermal allodynia in a rodent model of chronic central pain after spinal cord injury

Spinal cord injuries (SCI) result in a devastating loss of function and chronic central pain syndromes frequently develop in the majority of these patients. The present study uses a rodent spinal hemisection model of SCI in which mechanical and thermal allodynia develops by 24 days after injury. Post-operative paw withdrawal responses to low threshold and high threshold mechanical stimuli compared to pre-operative responses (4.78, 9.96, and 49.9 mN) were increased and were statistically significant (p<0.05) for both forelimbs and hindlimbs indicating the development of mechanical allodynia. By contrast, post-operatively, the temperature at which paw withdrawal accompanied by paw lick occurred was significantly decreased (p<0.05), indicating the development of thermal allodynia. The intrathecal application of either D-AP5, a competitive NMDA receptor antagonist, or NBQX-disodium salt, a competitive non-NMDA AMPA/kainate receptor antagonist, alleviated the mechanical allodynia and lowered the threshold of response for the high threshold mechanical stimuli in a dose-dependent manner, and these decreases were statistically significant (p<0.05). By contrast, neither the D-AP5 nor the NBQX produced a statistically significant change in the thermal allodynia behavior in either forelimbs or hindlimbs in the hemisected group. No significant changes in locomotion scores, and thus no sedation, were demonstrated by the hemisected group for the doses tested. These data support the potential efficacy of competitive excitatory amino acid receptor antagonists in the treatment of chronic central pain, particularly where input from low threshold mechanical afferents trigger the onset of the painful sensation. Furthermore, these data suggest a role for both NMDA and non-NMDA receptors in the development of plastic changes in the spinal cord that provide the underlying mechanisms for central neuropathic pain.     

Variability of sensory threshold determination in clinical use

The variability of perception threshold determination for vibration, tactile stimuli and thermal stimuli, with instruments intended for clinical use, was studied in 13 healthy subjects and 27 patients with chronic polyneuropathy. Normal thresholds for tactile and thermal stimuli were determined in 51 healthy subjects. Determinations were made for vibration on hand, lower leg and foot, for touch on pulp of forefinger and great toe and for temperature on hand and foot. Normal thresholds for both tactile and thermal stimuli were age-dependent. Short-term variation, with intervals of some minutes between determinations, remained within 8–18% change from first value. Long-term variation, with intervals of days to some weeks, was pronounced for all types of threshold, with extremes of ?90% and +256% change from first determination in 3 or 4 subsequent determinations. Variation was most marked for tactile stimuli and smallest for vibration, but magnitude and pattern of variation was similar for all sensory modalities and for both patients and healthy subjects. Confidence intervals, derived from analysis of variance, showed that as an average a change of < ?60% or > + 150% from the initial value was needed to ascertain with 95% probability that a subsequent value will reflect a true change of sensory threshold. Basing every threshold value on 2 or more measurements per occasion will reduce the confidence interval.The main cause of variability seems to be central processing mechanisms, i.e. the psychological variability. With proper attention to the variability, sensory threshold determinations should still be a valuable aid in clinical practice and clinical research.     

Development of mechanical and thermal nociceptive threshold testing devices in unrestrained birds (broiler chickens)

Behavioural signs of pain are difficult to quantify and interpret in animals. Nociceptive threshold testing is therefore a useful method for examining the perception and processing of noxious stimuli underlying pain states. Devices were developed to measure response thresholds to quantified, ramped mechanical and thermal nociceptive stimuli applied to the leg or keel of unrestrained birds. Up to 9 N mechanical force was delivered via a single round-ended 2 mm pin using a pneumatic actuator at 0.4 N s⁻¹. Heat was applied through a small copper element at 0.8 °C s⁻¹ to a maximum of 50 °C. The repeatability and reliability of threshold measures were validated using 10-12 broiler chickens (aged 49-66 days) per site and modality. Mechanical threshold, or skin and threshold temperature, were recorded over three sessions across a 36 h period. Both stimulus types elicited clear, reproducible behavioural responses. Mechanical threshold means and 95% confidence intervals were 3.0 (2.8-3.2) N for keel and 2.0 (1.8-2.1) N for leg sites. Keel thermal tests gave a mean skin temperature of 39.3 (39.1-39.5) °C, and threshold of 46.8 (46.6-47.1) °C. Leg skin temperature was 35.7 (35.6-35.9) °C and threshold 42.5 (42.2-42.8) °C. Threshold measures were consistent within and across sessions and birds showed individual repeatability across tests within sessions. Individual birds’ mechanical keel thresholds were also repeatable across sessions. The apparatus gave reliable, reproducible measurements of thresholds to noxious mechanical and thermal stimuli. The range recorded was comparable with previously published nociceptor thresholds in dissected chicken nerve filament fibres, and the method appears suitable for studying nociceptive processes in broiler chickens.     

Cutaneous thermal thresholds in patients with painful burning feet.

Small nerve fibre sensory function was assessed by psychophysical estimates of cutaneous thermal thresholds in 30 patients who presented with the symptoms of painful burning feet. Thresholds were abnormal in 12 and normal in 18 patients although symptoms in the two groups were very similar. Various hypotheses for the mechanism of pain in small fibre neuropathy have been proposed previously and these are discussed, but the cause of symptoms in patients with normal thresholds, is unknown. The possibility exists that these patients have a neuropathic disorder which affects only those unmyelinated fibres involved with pain.     

Spontaneous pain, pain threshold, and pain tolerance in Parkinson��s disease

The mechanisms underlying pain in Parkinson's disease (PD) are unclear. Although a few studies have reported that PD patients may have low pain threshold and tolerance, none could accurately assess whether there was a correlation between sensory thresholds and demographic/clinical features of PD patients. Thus, tactile threshold, pain threshold, and pain tolerance to electrical stimuli in the hands and feet were assessed in 106 parkinsonian patients (of whom 66 reported chronic pain) and 51 age- and sex-matched healthy subjects. Linear regression models determined relationships between psychophysical parameters and demographic/clinical features. Female gender, severity of disease, medical disease associated with painful symptoms, and dyskinesia were more frequently observed in PD patients experiencing pain, even though dyskinesia did not reach significance. Pain threshold and pain tolerance were significantly lower in PD patients than in control subjects, whereas the tactile threshold yielded comparable values in both groups. Multivariable linear regression analyses yielded significant inverse correlations of pain threshold and pain tolerance with motor symptom severity and Beck depression inventory. Pain threshold and pain tolerance did not differ between PD patients with and without pain. In the former group, there was no relationship between pain threshold and the intensity/type of pain, and number of painful body parts. These findings suggest that pain threshold and pain tolerance tend to decrease as PD progresses, which can predispose to pain development. Female gender, dyskinesia, medical conditions associated with painful symptoms, and postural abnormalities secondary to rigidity/bradikinesia may contribute to the appearance of spontaneous pain in predisposed subjects.     

No adrenergic sensitization of afferent neurons in painful sensory polyneuropathy

Introduction The aim of the present study was to determine (1) if an adrenergic sensitivity of afferent neurons is present in patients with painful polyneuropathy as compared with non–painful polyneuropathy and (2) if there is a correlation between adrenergic sensitisation and the severity of afferent and sympathetic small fiber damage. Methods 10 patients with painful and non painful polyneuropathy and 10 healthy controls were included. The function of small afferent and efferent sympathetic neurons was evaluated. Adrenergic sensitivity of afferent neurons was assessed by cutaneous iontophoresis of norepinephrine. Spontaneous pain, mechanical hyperalgesia as well as warm and heat pain thresholds were measured. Results Iontophoresis of norepinephrine did not induce or enhance spontaneous pain or mechanical allodynia, either in painless or painful polyneuropathies. There was no difference in norepinephrineinduced heat hyperalgesia between both neuropathy groups and healthy controls. The response of afferent neurons to norepinephrine was not correlated with the severity of damage to afferent small fibers or efferent sympathetic vasoconstrictor neurons. Conclusion The results do not support the assumption that in painful polyneuropathies afferent neurons acquire an adrenergic sensitivity after nerve injury and that adrenergic stimulation leads to an exacerbation of spontaneous pain and thermal and mechanical hyperalgesia. This work was supported by the Deutsche Forschungsgemeinschaft (DFG Ba 1921/1–1/2), and the Bundesministerium für Bildung und Forschung (BMBF) Research Network “Neuropathic Pain” and an unrestricted educational grant from Pfizer, Germany.     

Spinal somatostatin SSTR2A receptors are preferentially up-regulated and involved in thermonociception but not mechanonociception

The present study was undertaken to investigate the role of spinal somatostatin SSTR2A receptors in nociceptive processing. SSTR2A receptor-like immunoreactivity was found in a dense network in the spinal cord of normal rats. With Western blot analysis a major band of approximately 80-85 kDa was detected. Both immunohistochemistry and immunoblot analysis indicated a significant increase in SSTR2A receptor content in the spinal cord 6 h after noxious thermal stimulation that lasted for at least 24 h. However, there were no notable changes in SSTR2A receptor content 3, 6, 12, or 24 h after noxious mechanical stimulation. Effects of intrathecally administered polyclonal antiserum to SSTR2A receptor (anti-SSTR2A) on thermal and mechanical pain thresholds were determined with behavioral tests. In normal rats, pretreatment with anti-SSTR2A (1 microl, intrathecal) did not affect paw withdrawal latency or pinch threshold. Hindpaw inflammation induced by complete Freund's adjuvant led to thermal and mechanical hyperalgesia as reflected by a robust decrease in paw withdrawal latency and pinch threshold. Significant attenuation of the thermal hyperalgesia was observed 3, 5, 7, 9, and 24 h after pretreatment with anti-SSTR2A. This effect disappeared in another 24 h. In contrast, pretreatment with anti-SSTR2A failed to exert any notable effect on adjuvant-induced mechanical hyperalgesia. The present findings provide the first evidence that SSTR2A receptors are responsible for thermal, but not mechanical, nociceptive transmission in the spinal cord. The results also suggest that somatostatin has an excitatory role in spinal nociceptive processing and that there are differential receptor responses to different types of noxious stimuli.     

Pain ratings at the thresholds are necessary for interpretation of quantitative sensory testing

Published databases of quantitative sensory testing (QST) for sensory thresholds provide a means for detecting deficits of the thermonociceptive sensory nervous system. These databases, however, do not assist in the assessment of neuropathic pain, which is characterized by pain or hyperalgesia, or both. We utilized the method of levels for innocuous thermal stimuli, warm and cool, and the method of limits for noxious thermal stimuli, hot pain and cold pain, to determine QST thresholds. Stimuli were applied to distal and proximal sites in the upper and lower limbs of 50 healthy volunteers, ranging in age from 19 to 59 years. Thresholds for innocuous and noxious stimuli in this study were similar to previously published results. The mean pain rating across all sites at thresholds for noxious heat and cold stimuli was 4.10, as rated on a 0-10 numeric scale. Suggestions are provided for combining threshold information for innocuous and noxious stimuli and related pain ratings for the evaluation of sensory nervous system function and, specifically, neuropathic pain.     

Quantitative Sensory Testing in adults with Tourette syndrome

IntroductionAbnormal sensory perceptions, for instance hypersensitivity to certain external stimuli or premonitory urges preceding tics, are core features in Gilles de la Tourette syndrome (GTS). Aberrant awareness of externally applied stimuli in terms of altered sensory perception thresholds might contribute to these sensory phenomena in GTS.MethodsWe used the well-established and standardized “Quantitative Sensory Testing” (QST) battery (German Research Network on Neuropathic Pain) to investigate 13 sensory parameters including thermal, mechanical/tactile and pain thresholds in 14 GTS patients without clinically significant comorbidities and 14 healthy controls matched for age and gender.ResultsThere were no relevant group differences in any of the 13 QST parameters and no specific QST pattern in GTS patients. There was no correlation between QST parameters and “Premonitory Urge for Tics scale” (PUTS) scores.ConclusionOur data show that the perceptual threshold detection of externally applied sensory stimuli is normal in adults with GTS. This indicates that other perceptual mechanisms, such as abnormal central sensorimotor processing and/or aberrant interoceptive awareness might underlie the clinically significant sensory abnormalities in GTS.