Assessment of thermotactile and vibrotactile thresholds for detecting sensorineural components of the hand-arm vibration syndrome (HAVS).

BACKGROUND: Thermotactile thresholds and vibrotactile thresholds are measured to assist the diagnosis of the sensorineural component of the hand-arm vibration syndrome (HAVS). OBJECTIVES: This study investigates whether thermotactile and vibrotactile thresholds distinguish between fingers with and without numbness and tingling. METHODS: In 60 males reporting symptoms of the hand-arm vibration syndrome, thermotactile thresholds for detecting hot and cold temperatures and vibrotactile thresholds at 31.5 and 125 Hz were measured on the index and little fingers of both hands. RESULTS: In fingers reported to suffer numbness or tingling, hot thresholds increased, cold thresholds decreased, and vibrotactile thresholds at both 31.5 and 125 Hz increased. With sensorineural symptoms on all three phalanges (i.e. numbness or tingling scores of 6), both thermotactile thresholds and both vibrotactile thresholds had sensitivities greater than 80% and specificities around 90%, with areas under the receiver operating characteristic curves around 0.9. There were correlations between all four thresholds, but cold thresholds had greater sensitivity and greater specificity on fingers with numbness or tingling on only the distal phalanx (i.e. numbness or tingling scores of 1) suggesting cold thresholds provide better indications of early sensorineural disorder. CONCLUSIONS: Thermotactile thresholds and vibrotactile thresholds can provide useful indications of sensorineural function in patients reporting symptoms of the sensorineural component of HAVS.

Central circuitries for body temperature regulation and fever.

Body temperature regulation is a fundamental homeostatic function that is governed by the central nervous system in homeothermic animals, including humans. The central thermoregulatory system also functions for host defense from invading pathogens by elevating body core temperature, a response known as fever. Thermoregulation and fever involve a variety of involuntary effector responses, and this review summarizes the current understandings of the central circuitry mechanisms that underlie nonshivering thermogenesis in brown adipose tissue, shivering thermogenesis in skeletal muscles, thermoregulatory cardiac regulation, heat-loss regulation through cutaneous vasomotion, and ACTH release. To defend thermal homeostasis from environmental thermal challenges, feedforward thermosensory information on environmental temperature sensed by skin thermoreceptors ascends through the spinal cord and lateral parabrachial nucleus to the preoptic area (POA). The POA also receives feedback signals from local thermosensitive neurons, as well as pyrogenic signals of prostaglandin E(2) produced in response to infection. These afferent signals are integrated and affect the activity of GABAergic inhibitory projection neurons descending from the POA to the dorsomedial hypothalamus (DMH) or to the rostral medullary raphe region (rMR). Attenuation of the descending inhibition by cooling or pyrogenic signals leads to disinhibition of thermogenic neurons in the DMH and sympathetic and somatic premotor neurons in the rMR, which then drive spinal motor output mechanisms to elicit thermogenesis, tachycardia, and cutaneous vasoconstriction. Warming signals enhance the descending inhibition from the POA to inhibit the motor outputs, resulting in cutaneous vasodilation and inhibited thermogenesis. This central thermoregulatory mechanism also functions for metabolic regulation and stress-induced hyperthermia.

Effects of corneal injury on ciliary nerve fibre activity and corneal nociception in mice: A behavioural and electrophysiological study.

BACKGROUND: Ocular surface diseases are among the most frequent ocular pathologies. Ocular pain following corneal injury is frequently observed in clinic. Corneal sensory innervation is supplied by ciliary nerves derived from ophthalmic division of the trigeminal ganglion. METHODS & RESULTS: Extracellular activity of the mouse ciliary nerve was first used to investigate the corneal responsiveness to chemical, mechanical and thermal stimulations in order to specifically study the responses of polymodal nociceptors, mechano-nociceptors and cold thermoreceptor in a control cornea. Then, in two models of corneal injury (repeated instillations of 0.02% benzalkonium chloride and corneal scraping), we first measured the corneal sensitivity to chemical (eye-wiping test) and mechanical (von Frey filaments) stimulation. Thereafter, we evaluated whether these corneal injuries modified the spontaneous and chemical stimulation-evoked activity of the ciliary nerve. Both models of injury induced a significant corneal chemical hypersensitivity correlated with an increase of the spontaneous activity of the ciliary nerve and a faster response of the ciliary nerve after a chemical stimulation. CONCLUSIONS: Overall, this study provides new insights into the functional aspects of corneal nerve fibre activity in mice after corneal injury. The increase in ciliary nerve activity may thus contribute to the development of ocular pain after corneal damage. SIGNIFICANCE: This study highlights the parallel increase in ciliary nerve activity and corneal sensitivity after corneal injury in mice. The strategy of combining ex vivo electrophysiological recordings of the ciliary nerve in mice and corneal sensitivity measurements therefore helps to uncover the functional aspects of corneal pain.

Pain, Dryness, and Itch Sensations in Eye Surface Disorders Are Defined By a Balance Between Inflammation and Sensory Nerve Injury.

Patients with corneal and conjunctival disorders report an array of ocular surface symptoms including stinging, foreign body sensation, and itching. The intensity and perceptual quality of these sensations and their duration, from brief intervals to long-term symptoms, also vary. We hypothesize that symptomatic differences across disorders reflect differences in the balance between ocular inflammation and nerve injury, with different conditions resulting from predominant effects of one of these, or a combined effect. This article provides an overview of corneal and conjunctival nerve cells, such as nociceptors and thermoreceptors, with descriptions of their morphological and molecular characteristics and their nerve-firing patterns and evoked sensations, as determined by earlier studies in animals and humans. Detailed descriptions of the changes in neuronal responses (such as abnormal responsiveness and spontaneous firing) due to local inflammation and nerve injury are provided, and assorted ocular surface disorders are discussed. Eye conditions in which inflammation is predominant include allergic conjunctivitis and photokeratitis, whereas nerve injury is the primary factor underlying complaints of dry eye after photorefractive keratectomy and in elderly patients. Both factors contribute substantially to dry eye disease and varicella-zoster infections. This model of the combined effects of inflammation and nerve injury serves to explain the different sensations reported in various eye surface disorders, including short-term versus chronic pain and dysesthesias, and may help to improve diagnoses and treatment methods.

Warm immersion recovery test in assessment of diabetic neuropathy--a proof of concept study.

The aim of this article was to present results of warm immersion recovery test in the diabetic foot with neuropathy using a liquid crystal-based contact thermography system. It is intended to provide a 'proof of concept' for promoting the role of supplementary thermal assessment techniques and evidence-based diagnosis of diabetic neuropathy. A total of 81 subjects from the outpatient department of MV Hospital for Diabetes, India, were assessed using a liquid crystal thermography system. Each subject was assigned to one of three study groups, that is diabetic neuropathy, diabetic non neuropathy and non diabetic healthy. The room temperature and humidity were consistently maintained at 24 degrees C and less than 50%, respectively, with air conditioning. The right foot for each subject was located on the measurement platform after warm immersion in water at 37 degrees C. Whole-field thermal images of the plantar foot were recorded for 10 minutes. Local measurements at the most prevalent sites of ulceration, that is metatarsal heads, great toe and heel, show highest temperature deficit after recovery for diabetic neuropathy group. The findings of the current study support the ones of a previous study by the authors, which used cold immersion recovery test for the neuropathic assessment of the diabetic foot. A temperature deficit between the recovery and the baseline temperature for the neuropathic group suggests degeneration of thermoreceptors. Thermal stimulus tests can be useful to validate the nutritional deficits' (during plantar loading and thermal stimulus) contribution in foot ulceration.

Functional and Morphologic Alterations in Mechanical, Polymodal, and Cold Sensory Nerve Fibers of the Cornea Following Photorefractive Keratectomy.

Purpose: To define the characteristics and time course of the morphologic and functional changes experienced by corneal sensory nerves after photorefractive keratectomy (PRK). Methods: Unilateral corneal excimer laser photoablation was performed in 54 anesthetized 3- to 6-month-old mice; 11 naïve animals served as control. Mice were killed 0, 3, 7, 15, and 30 days after PRK. Excised eyes were placed in a recording chamber superfused at 34°C. Electrical nerve impulse activity of single sensory terminals was recorded with a micropipette applied onto the corneal surface. Spontaneous and stimulus-evoked (cold, heat, mechanical, and chemical stimuli) nerve terminal impulse (NTI) activity was analyzed. Corneas were fixed and stained with anti-ß-Tubulin III antibody to measure nerve density and number of epithelial nerve penetration points of regenerating subbasal leashes. Results: Nerve fibers and NTI activity were absent in the injured area between 0 and 7 days after PRK, when sparse regenerating nerve sprouts appear. On day 15, subbasal nerve density reached half the control value and abnormally responding cold-sensitive terminals were recorded inside the lesion. Thirty days after PRK, nerve density was almost restored, active cold thermoreceptors were abundant, and polymodal nociceptor activity first reappeared. Conclusions: Morphologic regeneration of subbasal corneal nerves started shortly after PRK ablation and was substantially completed 30 days later. Functional recovery appears faster in cold terminals than polymodal terminals, possibly reflecting an incomplete damage of the more extensively branched cold-sensitive axon terminals. Evolution of postsurgical discomfort sensations quality may be associated with the variable regeneration pattern of each fiber type.

Impaired Nociception in the Diabetic Ins2+/Akita Mouse.

The mechanisms responsible for painful and insensate diabetic neuropathy are not completely understood. Here, we have investigated sensory neuropathy in the Ins2+/Akita mouse, a hereditary model of diabetes. Akita mice become diabetic soon after weaning, and we show that this is accompanied by an impaired mechanical and thermal nociception and a significant loss of intraepidermal nerve fibers. Electrophysiological investigations of skin-nerve preparations identified a reduced rate of action potential discharge in Ins2+/Akita mechanonociceptors compared with wild-type littermates, whereas the function of low-threshold A-fibers was essentially intact. Studies of isolated sensory neurons demonstrated a markedly reduced heat responsiveness in Ins2+/Akita dorsal root ganglion (DRG) neurons, but a mostly unchanged function of cold-sensitive neurons. Restoration of normal glucose control by islet transplantation produced a rapid recovery of nociception, which occurred before normoglycemia had been achieved. Islet transplantation also restored Ins2+/Akita intraepidermal nerve fiber density to the same level as wild-type mice, indicating that restored insulin production can reverse both sensory and anatomical abnormalities of diabetic neuropathy in mice. The reduced rate of action potential discharge in nociceptive fibers and the impaired heat responsiveness of Ins2+/Akita DRG neurons suggest that ionic sensory transduction and transmission mechanisms are modified by diabetes.

Influence of height on quantitative sensory, nerve-conduction, and clinical indices of diabetic peripheral neuropathy.

We have examined associations between height and quantitative sensory, nerve-conduction, and clinical indices of diabetic peripheral neuropathy in adult diabetic patients. Vibratory sensitivity was strongly related to height when measurements were made with either the vibration sensitivity tester (P = .02) or the biothesiometer (P less than .01); however, there was no relation between thermal sensitivity (as measured with the thermal sensitivity tester) and height. The peroneal and posterior tibial motor nerve-conduction velocities were inversely related to height (P less than .05 for both). When age and diabetes duration were included as variables in multiple regression analyses, the associations with height became stronger. Clinical indices of peripheral neuropathy were also related to height in these analyses. Glycosylated hemoglobin was significantly related to thermal sensitivity and the peroneal and posterior tibial motor nerve-conduction velocities but not to vibratory sensitivity. These data indicate that height has a marked influence on quantitative sensory, nerve-conduction, and clinical indices of diabetic peripheral neuropathy.

Pathophysiology of empty nose syndrome.

OBJECTIVES/HYPOTHESIS: To review current knowledge on nasal airflow sensation in relation to empty nose syndrome (ENS). STUDY DESIGN: PubMed searches. METHODS: Current literature pertaining to measurement of nasal patency, mechanism of sensory perception of nasal airflow, and ENS. RESULTS: A reliance on pure anatomical analysis of the anatomy in ENS falls short of explaining the disorder. Our understanding of subjective nasal sensation has advanced, as has our understanding of the flow of air through the nose. Neural healing following a surgical insult may not result in a return to a normal physiologic state. Aberrations in neurosensory systems from improper healing may play a major role in the abnormal sensations ENS patients experience. CONCLUSIONS: An evidence-based hypothesis for the development and symptoms of ENS is offered.

Thermoregulatory dysfunction in neuroleptic malignant syndrome.

Hyperthermia is the central feature of neuroleptic malignant syndrome (NMS), but its etiology remains elusive. Two competing hypotheses implicate either hypothalamic dysfunction (inappropriate "set point") or direct myotoxicity (excessive peripheral heat production). These two models have distinct implications for thermoregulatory activity in NMS. The first predicts that the individual should respond as to a hypothermic threat or infection (the hypothalamus signals the body to raise its temperature). The second implies that an excessive heat load is perceived by the hypothalamus, which responds to this hyperthermic threat (it signals the body to lower its temperature). To assess the validity of these two hypotheses the thermoregulatory responses of a series of NMS patients (36 patients, 46 episodes) were examined using standard statistical methods. In contrast to normal mammalian thermoregulatory behavior, thermoeffector responses were not organized into either mode, but appeared to function somewhat independently and paradoxically. We conclude that neither hypothesis is sufficient to explain altered thermoregulation in NMS, and that the loss of integrated thermoeffector activity may be unique to this disorder.

Relation between intradental nerve activity and estimated pain in man--a mathematical model.

Intradental nerve activity (INA) induced by cold stimulation of human teeth is regularly accompanied by pain perception. In this study a mathematical model was developed in order to quantify the relationship between INA and pain. In 5 patients (45 experiments) INA was recorded using electrodes implanted in lower incisor teeth. Brief cold stimulations induced bursts of INA. The intensity of the resulting pain was simultaneously evaluated by means of an intermodal matching technique, finger span. The relationship between perceived pain and the integrated INA was analyzed using various mathematical operations (inter alia Fourier analysis) by means of a computer. A transfer function which describes the pain response following INA was found. This preliminary mathematical model, which is characterized by 5 parameters, consists of 2 parts, one which responds to fast changes in the afferent nerve signal, and another which reacts with a delay. The validity of the model has been tested, and it was found that the model consists of an adequate number of parameters and their cross-interaction is low. The analysis indicates that the parameters which determine the pain response following INA can be quantified and that they might be used as a measure of the efficacy of various pain relieving procedures.

Thermal stimulation of the hypothalamus does not evoke the acute-phase reaction.

Interleukin-1 (IL1) injected into the preoptic-anterior hypothalamus (POAH) induces, besides fever, the hepatic synthesis of acute-phase glycoproteins. Since the febrigenic action of IL1 may involve thermosensitive neurons in the POAH, this study examined whether such neurons also might mediate the acute-phase response (APR). The POAH of six adult NZW rabbits was cooled (Tpo = 34.4 +/- 0.4 degrees C [mean +/- SD]) or heated (40.6 +/- 0.2 degrees C) continuously for 2.5 hr (so as to mimic the mean febrile course following a bolus microinjection of IL1 into the POAH). The ambient temperature (Ta) was 23.5 +/- 1.0 degrees C. Expectedly, core temperature fell and skin temperature rose on POAH heating, and the opposite occurred on POAH cooling. However, no statistically significant changes in the plasma levels of Fe, Zn, Cu, and N-acetylneuraminic acid, as indices of the APR, were induced by these treatments. These results indicate, therefore, that the central actions of IL1 in inducing fever and the APR are separate, and that the APR is not mediated through stimulation of thermosensitive units in the POAH.

Pain responsivity in major depression and bipolar disorder.

Signal detection theory measures of thermal pain responsivity were examined in patients with major depression and bipolar disorder and in control subjects. Patients with major depression had significantly poorer sensory discrimination of painful thermal stimuli than control subjects, but they did not differ from the control subjects in their sensory discrimination of warm thermal stimuli of lower intensity. Patients with bipolar disorder did not differ significantly in sensory discrimination from either the patients with major depression or the control subjects. Patients with major depression had significantly higher (i.e., more stoical) response criteria than the control subjects for the painful thermal stimuli and also for the lower intensity stimuli; patients with bipolar disorder had significantly higher criteria than control subjects for only the lower intensity stimuli. The results suggest that reduced responsivity to pain in major depression may reflect sensory as well as affective abnormalities. Complaints of pain are very common in mood disorders, and continued examination of experimental pain in individuals with these disorders has the potential to enhance our understanding of this phenomenon.

[Use of the method of pulsed thermopuncture in the treatment of patients with chronic alcoholism during therapeutic remission]. / Primenenie impul'snoi teplopunktury v lechenii bol'nykh khronicheskim alkogolizmom v terapevticheskoi remissii.

The paper is concerned with pulse thermopuncture, a new method of reflexotherapy. Its modes and parameters, indications for clinical use are based. The method is especially indicated in the treatment of patients with vegetovascular and neurotic disorders. It provided a beneficial effect in the treatment of chronic alcoholics in a state of therapeutic remission in order to correct the above-indicated disorders and prevent the disease relapses.

[Raynaud's phenomenon]. / Fenomenologiia Reino.

Raynaud's phenomenon is a pathological condition with a multicomponent pathogenesis characterizing the community of mechanisms of the reactivity of the terminal microvessels of the extremities in response to standard stimulation. Raynaud's phenomenon is not a nosological form. In discovering Raynaud's phenomenon, however, differential diagnosis must be conducted to recognize the disease which caused the phenomenon. The diagnosis of Raynaud's disease, which is a nosological form, can be established by the method of exclusion of all such diseases. Raynaud's syndrome in the existence of diseases which are the primary cause is merely a precise diagnostic formulation.

[Restoration of sensation in free skin transplants]. / O vosstanovlenii chuvstvitel'nosti svobodnykh kozhnykh transplantatov.

Under study was the reestablishment of the pain, tactile and thermal sensitivity in free skin grafts in 265 patients in the period from 2-3 weeks till 25 years after free skin plasty for burn sequellae. The pain sensitivity was found to appear by the end of the first month. The tactile sensitivity was reestablished not earlier than within 1,5 month. The first signs of the thermal sensitivity made their appearance within the terms of from 3 to 6 months. By the end of the year the reestablishment of sensitivity was not accomplished.

Corneal sensory nerve activity in an experimental model of UV keratitis.

PURPOSE: To produce in guinea pigs a UV-induced keratitis, to analyze the effects of this pathology on corneal nerve activity. METHODS: In anesthetized animals, one eye was exposed to 254 nm UV-C radiation (500-1000 mJ/cm(2)), excised 24 to 48 hours later and superfused in vitro. Nerve impulse activity was recorded in ciliary nerve filaments or in corneal sensory terminals of intact and UV-irradiated eyes. Impulse activity in response to mechanical (von Frey hairs), chemical (98.5% CO2 gas jets), and thermal stimulation (cooling from 34°C to 20°C; heating to 50°C) was analyzed. Duration of eyelid closure and blinking and tearing rates were evaluated in control and in UV-irradiated eyes, before and after application of TRPV1, TRPA1, and TRPM8 agonists (100 µM capsaicin; 10 mM AITC, and 200 µM menthol, respectively). RESULTS: After irradiation, mechanical threshold of mechano-nociceptor corneo-scleral fibers was reduced (0.59 ± 0.4 vs. 0.27 ± 0.07 mN; P < 0.05) while polymodal nociceptors increased their response to chemical stimulation (1.7 ± 0.2 vs. 3.4 ± 0.5 imps/s; P < 0.05). In contrast, cold thermoreceptors showed a significantly lower ongoing activity at 34°C (8.6 ± 0.5 vs. 6.1 ± 0.9 imp/s; P < 0.05) and a reduced responsiveness to cooling pulses (peak frequency = 29.8 ± 1.3 vs. 18.9 ± 1.8 imp/s; P < 0.001). Blinking but not tearing rate was significantly higher; behavioral responses to topical capsaicin and AITC, but not to menthol were enhanced in UV-irradiated animals. CONCLUSIONS: Sensitization of nociceptor and depression of cold thermoreceptor activity following UV radiation appear to result from an action of inflammatory mediators on TRP channels selectively expressed by sensory nerve terminals. Changes in nerve activity possibly underlie discomfort sensations associated with corneo-conjunctival inflammation induced by UV exposure.

[Antipyretic effect of moxibustion at different temperatures and its relationship with the activity of temperature sensitive neurons in thermotaxic center].

OBJECTIVE: To discover the central mechanisms of antipyretic effect of moxibustion and its relationship with the acupoint sensor so as to provide the scientific evidence for "the treatment of heat syndrome with moxibustion". METHODS: Eighteen New Zealand Rabbits were randomly assigned into three groups, named group A (modeling with intravenous injection of Endotoxin), group B (moxibustion at 40 degrees C after Endotoxin injection) and group C (moxibustion at 48 degrees C after Endotoxin injection), 6 rabbits in each one. The experiment was undergoing in the condition of muscular relaxation and artificial respiration for the animals. The spotlight moxibustion at constant temperature was applied to "Zhiyang" (GV 9). The discharge of heat sensitive neurons (HSNs) at the preoptic region and anterior hypothalamus (POAH) was taken as the index. The impacts of the treatment on HSNs were observed in each group. RESULTS AND CONCLUSION: Moxibustion had significant antagonism to the pyrogen on its inhibition to the activity of HSNs in the thermotaxic center. As a result, the antipyretic effect was obtained. It is concluded that the effective result of moxibustion is achieved by stimulating polymodal receptors of acupoints.