Changes In Sensory Thresholds Research Articles

Quantitative Sensory Testing in Cluster Headache: Increased Sensory Thresholds

To determine if recently reported changes in sensory thresholds during migraine attacks can also be seen in cluster headache (CH), we performed quantitative sensory testing (QST) in 10 healthy subjects and in 16 patients with CH. Eight of the patients had an episodic CH and the other eight a chronic CH. The tests were performed on the right and left cheeks and on the right and left side of the back of the hands to determine the subjects' perception and pain thresholds for thermal (use of a thermode) and mechanical (vibration, pressure pain thresholds, pin prick, von Frey hairs) stimuli. Six patients were examined in the attack-free period. Three were also willing to repeat the tests a second time during an acute headache attack, which was elicited with nitroglycerin. The healthy subjects performed the experiments in the morning and evening of the same day to determine if sensory thresholds are independent of the time of day. If they were, this would allow estimation of the influence of the endogenous cortisone concentration on these thresholds. The control group showed no influence of the time of day on the thresholds. There was a significant difference in pain sensitivity between the back of the hands and the cheeks (P<0.05): higher thresholds were found on the back of the hands. The thresholds generally exhibited little intersubject variability, indicating that QST is a reliable method. There was also a significant difference between the test areas in the patient group (P<0.001): the cheeks were also more sensitive than the back of the hands. In comparison with reference data of healthy volunteers, the detection thresholds were increased in the patients on both test areas. These were statistically significant for warmth, thermal sensory limen (TSL), heat and pressure on the back of the hands (P<0.04) and for the warmth and TSL thresholds on the cheeks (P<0.05). There were no differences in the thresholds regardless of whether the patients were examined in or outside of a cluster bout. Furthermore, we found no cutaneous allodynia in the three patients tested during an attack. The increased sensory thresholds on the cheeks as well as on the back of the hands are in agreement with an increased activation of the patients' antinociceptive system. The seasonal variation and the temporal regularity of single attacks as well as the findings in imaging studies indicate that the hypothalamus is involved in the pathophysiology of CH. In view of the strong connectivity between the hypothalamus and areas involved in the antinociceptive system in the brainstem, we hypothesize that this connection is the reason for the increased sensory thresholds in CH patients found in our study.

Neurochemistry of Trigeminal Activation in an Animal Model of Migraine

Research techniques such as electrophysiology, cFos protein expression, and other measurements of neuronal activation provide insights into the pathophysiology of pain processing in migraine, but they do not indicate the specific neurotransmitter systems involved. This paper summarizes data from microdialysis experiments in which changes in the neurochemistry of the trigeminal nucleus caudalis (TNC) were monitored during dural stimulation. Microdialysis allows the measurement of extracellular concentrations of neurotransmitters in a small area of the brain, in vivo, by means of a probe equipped with a semipermeable membrane. Microdialysis enables direct measurement of changes in extracellular concentrations of neurotransmitters in the intact animal over time in response to dural inflammation. Following the activation of the dural nociceptors, changes in the extracellular amino acid neurotransmitters in the deep lamina of the TNC were tracked. A 5-minute application of inflammatory soup when compared with saline to the dura of rats induced a transient decrease in extracellular glutamate in the TNC at approximately 30 minutes postapplication. This short-lived decrease was followed by a continuous increase in extracellular glutamate to a level of approximately 3 times the baseline value at 3 hours after application of the inflammatory soup. The time course of this increase in extracellular glutamate correlated with changes in sensory thresholds on the face of the rat from electrophysiological recordings of secondary sensory neurons in the TNC. No significant differences between the inflammatory soup and saline conditions were observed for extracellular concentrations of aspartate (an excitatory amino acid) or the inhibitory neurotransmitters gamma-aminobutyric acid or glutamine. Results of these experiments support an integral role for glutamate in central sensitization of neurons in the TNC, and suggest an important contribution of glutamate to allodynia and hyperalgia in this animal model of migraine.

Changes to cold detection and pain thresholds following low and high frequency transcranial magnetic stimulation of the motor cortex

There is some evidence that repetitive transcranial magnetic stimulation (rTMS) can alleviate the experience of chronic pain. The mechanisms by which rTMS may induce pain relief, however, are unknown. The present study examined whether a session of rTMS would produce sensory threshold changes in healthy individuals. Detection and pain thresholds for cold sensations were compared following low frequency (1 Hz) (Experiment 1) and high frequency (20 Hz) (Experiment 2) repetitive TMS. While cold detection threshold was significantly lowered by both rTMS rates, only high frequency rTMS produced a significant change in cold pain threshold. In contrast, sham rTMS did not alter thresholds for cold stimuli. These findings provide evidence that sensory thresholds can be influenced by repetitive transcranial magnetic stimulation.

Pathogenesis of sciatic pain: a study of spontaneous behavior in rats exposed to experimental disc herniation.

A new way to study pain in experimental animals without handling of the animals and based on registration of spontaneous behavior using video recordings. To evaluate if experimental disc herniation in the rat may induce changes in spontaneous behavior. The knowledge regarding the basic pathophysiologic mechanisms of sciatica has increased dramatically during the last decade. However, studies have mainly assessed nerve dysfunction rather than pain. Existing methods to study pain generally comprise a certain amount of handling and registration of changes in sensory thresholds. In the present study we introduce a new way to assess pain that focuses on changes in behavior rather than on changes in thresholds. Forty rats were divided equally into four experimental series: sham exposure of the left L4 dorsal root ganglion, exposure of the left L4 dorsal root ganglion and incision of the L4-L5 disc, exposure and slight displacement of the left L4 dorsal root ganglion, and combination of disc incision and displacement. The rats were videotaped the day before surgery and on day 1, 3, 7, 14, and 21 after surgery. Spontaneous behavior was categorized into 10 behaviors and recorded during 20 minutes of observation. Disc incision and displacement per se did not induce any behaviors different from that observed in the sham-operated group. In the series with the combination of disc incision and displacement there was increased focal pain, seen as increased lifting of the hind paw on the operated side and increased rotation of the head toward the operated side. This pain pattern was most pronounced the day after surgery. Fourteen days after surgery there were no detectable differences in behavior between this group and the sham group. At day 21 after surgery, however, another picture of increased immobility and decreased locomotion was seen in this group, possibly indicating more generalized pain. The study demonstrates that it is possible to detect changes in spontaneous behavior after experimental disc herniation. However, such changes may only be seen if disc incision and slight mechanical deformation are combined. This is in agreement with previous clinical and experimental observations. The present model allows for convenient assessment of pain in a way that focuses on spontaneous behavior rather than changes in pain thresholds and that reduces the interference of the researcher and environment on the outcome of the assessment.

An analysis of changes in sensory thresholds to mild tactile and cold stimuli after experimental spinal cord injury in the rat.

Changes in sensory function including chronic pain and allodynia are common sequelae of spinal cord injury (SCI) in humans. The present study documents the extent and time course of mechanical allodynia and cold hyperalgesia after contusion SCI in the rat using stimulation with graded von Frey filaments (4.97-50.45 g force) and ice probes. Fore- and hind-paw withdrawal thresholds to plantar skin stimulation were determined in rats with a range of SCI severities (10-g weight dropped from 6.25, 12.5, or 25 mm using the MASCIS injury device); animals with 25-mm injuries most consistently showed decreased hind-paw withdrawal thresholds to touch and cold, which developed over several weeks after surgery. Stimulation of the torso with graded von Frey hairs was performed at specified locations on the back and sides from the neck to the haunch. Suprasegmental responses (orientation, vocalization, or escape) to mechanical stimulation of these sites were elicited infrequently in the laminectomy control rats and only during the first 3 weeks after surgery, whereas in 25-mm SCI rats, such responses were obtained for the entire 10 weeks of the study. These data suggest that rats with contusion SCI may exhibit sensory alterations relevant to human spinal cord injuries.

Elevation of sensory thresholds in the prostatic urethra after microwave thermotherapy.

To determine whether transurethral microwave thermotherapy (TUMT) affects the sensory threshold in the posterior urethra and whether such an effect influences urinary storage symptoms. The sensory threshold was measured before and at 3 and 12 weeks after TUMT in 13 men with minor obstructive symptoms caused by benign prostatic hyperplasia. Sensations were evoked by electrical stimulation at different frequencies, using a bipolar ring-electrode mounted on a urethral catheter. Changes in sensory thresholds were evaluated in the patients both as a group and individually. The patients were interviewed about their symptoms at each measurement. After TUMT, 12 patients were satisfied and reported decreased irritative symptoms, primarily less frequent nocturnal micturition; two patients were cured of urgency incontinence. In 11 of the satisfied patients, and the unsuccessful patient, decreased urge accompanied increased sensory thresholds. Thresholds elevated by >/= 30% were correlated with decreased irritative symptoms. TUMT decreases sensitivity in the posterior urethra, which may alleviate storage symptoms.

Pain and Somatosensory Dysfunction in Acute Herpes Zoster

To determine the nature of sensory change and its association with pain and allodynia in acute herpes zoster. Prospective clinical study. One hundred thirteen immunocompetent patients with acute herpes zoster. Onset, intensity, and quality of pain and severity of rash were recorded. Quantitative somatosensory testing for tactile and thermal thresholds, qualitative pinprick testing, and testing of dynamic and static allodynia were performed within the affected dermatome, its mirror-image dermatome, and in an adjacent dermatome bilaterally. Acute pain was reported as severe in 50%, moderate in 29%, mild in 12%, and absent in 9% of patients. Preherpetic pain (median = 4 days, range = 1-60 days) was experienced by 71%. Mechanical allodynia, dynamic, static, or both, was found in 37% of patients and was noted to extend one or more dermatomes outside the rash in 12%. In the affected dermatomes, thresholds were elevated for warmth and cold, lowered for heat pain, and unchanged for touch when compared with the contralateral side. Logistic regression analyses showed that compression-evoked allodynia, brush-evoked allodynia, and the history of preherpetic pain were more frequently encountered in patients with severe pain. Sensory threshold changes were not associated with the severity of pain or rash or with the presence of allodynia. Pain, allodynia, and altered sensation are common features of acute herpes zoster. They are likely to result primarily from widespread neural inflammation within the affected afferent system. The sensory changes found in acute herpes zoster are different from those reported in published studies on postherpetic neuralgia and suggest sensitization phenomena and preservation of tactile functions rather than major neural damage. The exact mechanisms for acute herpes zoster pain, however, remain speculative.

Sensory threshold changes without initial pain or alterations in cutaneous blood flow, in the area of secondary hyperalgesia caused by topical application of capsaicin in humans

Changes in von Frey hair perception, pricking pain, and vibration thresholds were examined in six healthy human adults, in the zone of secondary hyperalgesia, 45 min following the topical application of capsaicin at concentrations of 0.05 and 0.1 mg/ml. In two of these subjects, cutaneous blood flow was monitored at 10-min intervals, before, during and after capsaicin application, using laser Doppler perfusion imaging. Thresholds for all three parameters were significantly reduced after capsaicin treatment, in a dose-dependant manner. However, there was no visible skin flare, and no change in cutaneous blood flow at these doses of capsaicin. The effects on von Frey perception threshold and vibration threshold have not been demonstrated previously, and may be indicative of central changes, initiated by afferent fibres (presumably C fibres) that are not vasoactive.

Acupuncture for Gastrointestinal and Hepatobiliary Disorders

Acupuncture has been used for various gastrointestinal (GI) conditions. Voluminous data support the effect of acupuncture on the physiology of the GI tract, including acid secretion, motility, neurohormonal changes, and changes in sensory thresholds. Much of the neuroanatomic pathway of these effects has been identified in animal models. A large body of clinical evidence supports the effectiveness of acupuncture for suppressing nausea associated with chemotherapy, postoperative state, and pregnancy. Prospective randomized controlled trials have also shown the efficacy of acupuncture for analgesia for endoscopic procedures, including colonoscopy and upper endoscopy. Acupuncture has also been used for a variety of other conditions including postoperative ileus, achalasia, peptic ulcer disease, functional bowel diseases (including irritable bowel syndrome and nonulcer dyspepsia), diarrhea, constipation, inflammatory bowel disease, expulsion of gallstones and biliary ascariasis, and pain associated with pancreatitis. Although there are few prospective randomized clinical studies, the well-documented physiological basis of acupuncture effects on the GI tract, and the extensive history of successful clinical use of acupuncture, makes this a promising modality that warrants further investigation.

Differential effects of glucocorticoids on human auditory perception

It is assumed that glucocorticoids and mineralocorticoids, the hormones produced by the adrenal cortex, act as modulators of central nervous functions in addition to their well known role in endocrine stress responses. More specifically, it has been suggested that adrenal corticoids cause changes in sensory thresholds. In two double-blind crossover studies we evaluated auditory perception in healthy volunteers after treatment with hydrocortisone, dexamethasone, and the respective placebos. Stapedial reflexes, pure tone and speech audiograms, and brainstem electric response audiometry served as the dependent variables. As circadian changes in the density and occupancy of the brain corticosteroid receptors have been postulated, we performed Study I in the morning and Study II in the evening. Treatment effects clearly varied with time of day. A differential effect of the two corticoids occurred on contralateral stapedial reflexes. These results parallel results obtained with gustatory stimuli, and suggest that glucocorticoids modulate sensory perception across modalities.

Evaluation of patients with thoracic outlet syndrome

This prospective study evaluated 50 patients with thoracic outlet syndrome. Detailed history and pain scale evaluation preceded physical examination, which included provocative tests (positional and compressive) and sensory evaluation (baseline and postprovocative vibration thresholds and two-point discrimination). Only one patient had a positive nerve conduction study/electromyograph at the brachial plexus level. Thirty-two percent of the patients had a compressive anatomic abnormality as seen on a computed tomography scan. Ninety-four percent had positive provocative position and compression test results. Two-point discrimination was normal in 98%. Clinical assessment of thoracic outlet syndrome is best achieved by reproduction of symptoms with compression and positional provocative testing. Results of the majority of tests (nerve conduction studies/electromyographs, x-ray films, sensory tests) will be normal. Measurements of changes in sensory thresholds during provocation of symptoms may be useful.

A prospective study of sensory function in patients with type 2 diabetes.

Sensory function was prospectively examined in 201 Type 2 diabetic patients over a 2-year period. Quantitative sensory testing for vibration, cool, warm, and pressure perception at the hallux was performed at baseline, 1-month, 1-year, and 2-year visits. There were statistically significant increments of thresholds for all sensory modalities from the baseline visit to the 1-year visit (p < 0.001) and from the 1-year visit to the 2-year visit (p < 0.001). Thirty percent of 77 subjects considered to be at low risk for foot ulceration at baseline progressed to a higher risk category at the 2-year visit. There were no significant differences in mean glycosylated haemoglobin, height, sex distribution, age, or diabetes duration when patients who had a faster progression of insensitivity were compared with patients who had a slower progression. There was a high degree of autocorrelation between baseline and 2-year visits for all sensory modalities (r = 0.83 to r = 0.88, p < 0.001 for all). Also, changes in sensory thresholds from the baseline to 2-year visits for one modality tended to correlate with other modalities (r = 0.36 to r = 0.70, p < 0.001 for all). These data indicate that an appreciable proportion of Type 2 diabetic patients are at risk for a marked rate of decline of sensory function, and suggest a need for at least yearly quantitative sensory testing.

Scopolamine does not affect footshock sensitivity in the rat

To test the generality of the finding of Feigley, et al. [8] that scopolamine increases sensitivity/reactivity to footshock, rats were tested under either scopolamine or saline conditions for sensitivity to footshock in an automated version of the flinch-jump paradigm. There was no significant trend toward increased sensitivity following scopolamine injection at any of the response magnitudes assessed. Since the previous study included an operant response in the measure of sensitivity, it was suggested that apparent effects of scopolamine on reactivity to footshock are dependent on the inclusion of an operant response in the measure of reactivity, and are not due to changes in sensory thresholds.

Cross-modal induction of changes in sensory thresholds.

Two experiments are reported in which subliminal stimulation of one modality with emotional material impairs detection performance in a different modality. In the first experiment the visual awareness threshold for neutral material was raised by simultaneous auditory presentation of emotional words. This result supports the hypothesis that threshold changes induced by emotional stimulation are mediated centrally. In the second experiment a similar effect was obtained when the experimental roles of the two modalities were reversed. An analysis of the effect in terms of the parameters of Signal Detectability Theory indicates that it is mediated by a lowering of the sensitivity of the detection mechanism. This may be caused either by attenuation of incoming signals, or by an increase in the level of “noise” against which the signal is received.

The role of the superior colliculus in visually guided behavior

Unilateral lesions in the superior colliculus of the cat which do not involve the tegmentum result in two major behavioral signs: an homonymous field defect with complete or relative neglect of stimuli in the visual fields contralateral to the lesion, seen particularly in extinction of the contralateral response when rival stimuli are used; and a motor deficit in appropriate movements of eyes, head and body, expressed in ipsiversive forced circling and an heightened compulsive response to ipsilateral stimuli. These signs are not related to changes in pupils or in accommodation. Associated with these are abnormal responses to contralateral acoustic, tactile and sometimes nociceptive stimuli, appearing primarily as inappropriate localization of the stimuli rather than as changes in sensory threshold. The two major deficits are separable by means of smaller lesions in various parts of the afferent and efferent tectal pathways. Lesions of the tectospinal tract result in the motor deficit without the visual neglect. Involvement of the brachium of the superior colliculus and of parts of the tectothalamic system yield a contralateral visual neglect without the motor deficit. Bilateral collicular lesions result in apparent initial blindness and enduring deficits in visual following, in localization of stationary stimulus objects, in a disability to look up and in poor localization to tactile stimulation of the hind legs. We conclude that the functions of the superior colliculus include that of visual attention and perception as well as the classically accepted control of the movements of head and eyes.