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Biomedical subjects

R A Westerman

Publications and source records attributed to R A Westerman.

At least 37 records · Page 2Linked to original sources

Noxious heat hyperalgesia test instrument.

A simple feedback thermode has been developed to quantify cutaneous hyperalgesia to noxious heat. A noxious temperature set between 42 degrees C and 60 degrees C is applied to a test site by the subject. A resettable impedance timing circuit measures the contact duration to +/- 0.01s. Despite site-to-site, inter- and intra-subject variability, the test sensitivity is enhanced by comparing affected and corresponding normal skin in the same subject. This test strategy was used in 55 subjects in whom topical 0.025 to 0.05% capsaicin application provoked hyperalgesia on the forearm and foot. Capsaicin-treated sites showed a significant reduction of 52 degrees C withdrawal latency (0.51-0.77 x normal mean; P less than 0.05). The device has been tested clinically in patients with diabetic neuropathy who had hypersensitivity to pinprick on one foot. A significant 42% difference was found between corresponding contralateral sites (P less than 0.05). These data suggest that even mild hyperalgesia is detectable using this instrument. It provides an objective measure of hyperalgesia which can be used to assess changes in nociceptive acuity.

Capsaicin↗

Properties of transdermal histamine iontophoresis: differential effects of season, gender, and body region.

Histamine iontophoresis is demonstrated to be a reliable model for the study of inflammatory skin responses. It has the advantage of a non-invasive and uniform mode of application and is free of unwanted side effects. The wheal and flare responses to histamine are linearly related to dose over a wide range of stimulus strengths (r = 0.88). In summer, wheal responses were smaller, probably due to increased thickness of the epidermis. Female subjects generally expressed larger wheal responses than males, presumably due to differences in epidermal thickness and structure. There were significant regional differences in wheal, flare, and laser Doppler recorded flux responses. Ratings of itch sensations also showed clear, but less pronounced, differences of body regions. Significant regional differences of wheal and flare responses existed. Sensory discrimination of different stimulus levels was demonstrated with visual analogue scale ratings.

Administration, Cutaneous↗

Neurogenic vasodilation in the rat hairy skin measured using a laser Doppler flowmeter.

Intradermal stimulation of the saphenous nerve of anesthetized rats at C-fiber strength elicited stimulus-dependent vasodilator responses in saphenous-innervated hairy skin. A laser Doppler flowmeter (Periflux, Pf1d) was used to measure these neurovascular responses non-invasively. Capsaicin pretreatment significantly attenuated the vasodilator response. Furthermore, intraperitoneal administration of atropine or mepyramine significantly reduced the skin vascular responses. The responses of halothane-anesthetized rats were significantly attenuated when compared with rats anesthetized with pentobarbitone. Results of this study suggest the presence of endothelium-dependent vasodilator peptidergic, cholinergic and histaminergic contributions to electrically-evoked axon reflex vasodilation in the rat hairy skin.

Animals↗

Observations on a new non-invasive monitor of skin blood flow.

1. A 'tissue perfusion monitor' (TPM) to non-invasively provide an index of skin blood flow (SkBF) has been developed; it employs photoelectric plethysmographic principles to measure changes in the nett flux of red blood cells in superficial microvasculature. 2. The 'tissue perfusion index' (TPI) varies in proportion to SkBF, provided local haemoglobin concentration does not change significantly. TPI of humans and experimental animals has been shown to indicate reliably, well established phenomena such as decreased SkBF in response to mechanical restriction, cold or Valsalva's manoeuvre, or increased SkBF in response to heat, acetylcholine, sodium nitrite or local nerve blockade. 3. SkBF in sheep was varied between 1 and 156 mL/100g per min as measured with radioactive microspheres. Simultaneous measurements were made using the TPM and four laser-Doppler instruments. The TPI yielded a correlation coefficient of 0.938, and when data were expressed as percentage change, the regression line did not differ significantly from the line of identity and the root-mean-square-error was 6.2%. Data for the laser-Doppler indices of SkBF were, respectively, 0.549-0.786, highly significant deviations in slopes, and 13.6-16.7%. 4. Thus, the TPI is a reliable index of changes in SkBF. Compared with some other available instruments, the TPM is more precise; it is also less sensitive to movement artefact, can be completely portable by battery operation, probes can be multiplexed to a single meter and it is likely to be much less expensive than current lasers. 5. Applications include, for example, experimental investigations of SkBF in man and animals, clinical uses such as evaluation of the efficacy of regional nerve blockade or of circulatory restitution after reconstructive surgery, and clinical tests of neurovascular function.

Adult↗

Concordance between different measures of small sensory and autonomic fibre neuropathy in diabetes mellitus.

This study presents concordance data from 3 different tests of small nerve-fibre function on the same diabetic patients and also examines the effects of hyperglycaemia. Thus the TTT-Glasgow automated thermal threshold test, EAR-Electrically evoked axon reflex flare, and GOE-Gastric emptying of a mixed sold/liquid meal and oesophageal emptying of a solid bolus were all measured on 25 diabetic patients. The TTT, EAR and GOE all gave values ranging from within the normal reference range for non-diabetics to markedly dysfunctional readings. Mean warm perception (WPT) on the foot dorsum averaged 0.73 degrees C +/- 0.93 for normal controls, but was 4.67 degrees C +/- 3.99 in the 25 diabetics. Cold perception thresholds (CPT) were 0.48 degrees C +/- 0.55 for normal subjects and 3.75 degrees C +/- 4.28 for diabetics. In the same normal subjects the mean EAR flare laser flux responses (for 8 and 16 noxious TENS pulses) was 2.8 V.min, while for diabetics the mean was 0.2 V.min. Solid and liquid gastric 50% emptying times and oesophageal emptying for non-diabetics were within normal range (mean 78 min and 18 min, 18 sec respectively) but for the 25 diabetics emptying times ranged from normal to very prolonged (mean 114 min and 30 min, 68 sec respectively). A plot of 3 measured variables (TTT, EAR and GOE) showed a high degree of correspondence between the gastro-oesophageal emptying delays and the presence of reduced electrical axon reflex and elevated thermal thresholds. Of 25 patients, 6 could be classed as within normal limits on all 3 variables, but 8 of 25 displayed objective evidence of C-fibre neuropathy--thermal perceptual impairment (C- and A-delta sensory fibres), reduced neurogenic inflammatory flare (peptidergic nociceptive afferents) and delayed gastro-oesophageal emptying (vagal afferent/efferent fibres).

Autonomic Nervous System↗

Identification of the physical stimulus and the neural basis of fabric-evoked prickle.

1. The neurophysiological basis for the sensation of prickle evoked by contact of some fabrics with the skin is reported. 2. Single-unit sensory nerve recordings from the rabbit saphenous nerve were used to identify the receptors responsible for fabric-evoked prickle. These recordings showed that all low-threshold mechanoreceptors were activated by fabric, but they did not show differential response to prickly and nonprickly fabrics. 3. However, the response of some nociceptors, both A delta and polymodal C, differed according to the prickliness of fabrics. Some of these receptors responded to fine von Frey hairs with buckling loads of at least 75 mgf. This suggested that the prickle stimuli on the fabric surface were protruding fiber ends that exerted loads of 75 mgf, or more, against the skin. 4. A Teflon replication technique was devised for estimating the density of these fiber ends. Estimates of the sensation magnitude of prickle from graded fabric sets by a panel of 55 subjects correlated (coefficient 0.91) with this measure of fiber end density. 5. We conclude from these results that fabric-evoked prickle is the result of low-grade activity in nociceptors and that the stimuli are protruding fiber ends exerting loads of approximately 75 mgf or more against the skin.

Action Potentials↗

Transcutaneous electrical stimulation and the sensation of prickle.

1. A high-voltage low-current transcutaneous electrical stimulating device was constructed and tested for its suitability to evaluate fabric-evoked prickle sensitivity in a population of 162 subjects. The initial sensation experienced by subjects with this device was the unpleasant sensation of prickle. 2. Single-unit recordings from the rabbit saphenous nerve established that at threshold most unmyelinated cutaneous receptors, both C low-threshold mechanoreceptive and polymodal nociceptive, were activated by the device. 3. Threshold measurements showed that there was no relationship of electrical threshold to atopic status, nor to fabric prickle threshold. It was concluded that our device preferentially excites unmyelinated afferents, but is not useful as a screening device for fabric intolerance.

Action Potentials↗

Effects of topical capsaicin on normal skin and affected dermatomes in herpes zoster.

Hyperalgesia and allodynia, lasting for months or even years, occurs in the form of post-herpetic neuralgia in approximately 70% of adults previously infected with the varicella herpes zoster virus. The present study aimed at testing the analgesic desensitising actions and reversibility of repeated application of topical capsaicin on disordered polymodal nociceptors and peptidergic sensory fibres mediating warm and pain sensation. Cutaneous nociceptor desensitisation was measured using the Glasgow automated thermal threshold test (Medelec TTT). For normal subjects (n = 69) the mean forearm warm threshold was 0.15 +/- 0.07 degrees C and the cold threshold was 0.14 +/- 0.10 degrees C. A variable degree of partial desensitisation of herpes-affected skin was found in 15 patients with post-herpetic neuralgia before capsaicin treatment where the mean threshold elevation for warm detection was 1.19 degrees C and 0.7 degrees C for cold detection, compared with the corresponding normal skin. In preliminary studies of 15 patients with post-herpetic neuralgia, good pain relief averaging 30% or 77% occurred in the affected dermatome(s) after 3 to 4 weeks of 0.01% or 0.05% capsaicin cream respectively, applied 3-4 times daily. The warm thresholds, after chronic capsaicin treatment, increased between 0.1 and 7.60 degrees C, the average elevation being 3.69 degrees C. By contrast cold thresholds after capsaicin altered inconsistently and by only an average of 0.08 degrees C. The results suggest that elevation of the warm threshold may indicate the desensitisation achieved by capsaicin treatment of skin polymodal nociceptors. Cold detection, being dependent upon A-delta cold fibre function, is unaffected by capsaicin treatment. There was a poor correlation between pain relief and elevation of warm detection in response to capsaicin treatment. Generally, it was found that those patients with less initial desensitisation to warm detection as a consequence of post-herpetic neuralgia experienced better pain relief after capsaicin was applied. The method used permits determination of the minimum effective desensitising dose of capsaicin, enables patient compliance and progress to be monitored and should allow the prediction of patients likely to achieve the best response to treatment.

Administration, Topical↗

Laser Doppler measurements of skin vasodilation elicited by percutaneous electrical stimulation of nociceptors in humans.

This study was designed to assess the quantitative features of the skin protecting mechanism of axon reflexes by monitoring stimulus related changes in skin blood flow using laser Doppler flowmetry. Skin vasodilatation induced by trains of brief transcutaneous electrical pulses (0.5 ms, 150 V) was strictly related in magnitude to the number of pulses (trains of 1-32). This vascular response was reduced by 95% when the skin had been pretreated by painting it for two days with a 1% alcoholic solution of capsaicin. The sensitivity of vascular responses to activation of afferent C-fibers indicates a role of this mechanism in the protection of the skin against noxious events.

Adult↗

Non-invasive tests of neurovascular function: reduced responses in diabetes mellitus.

Painful transcutaneous electrical nerve stimulation (TENS) of the foot dorsum evoked axon reflex vasodilatation, measured by laser Doppler flowmetry. In addition, acetylcholine (ACh) and sodium nitrite (NaNO2) were iontophoresed to cause vasodilatation by endothelium dependent and independent mechanisms, respectively. Compared with healthy volunteers, diabetic patients with clinically diagnosed neuropathy showed reduced electrical axon reflex flare and ACh responses, but not NaNO2 responses. Such reduced cutaneous nocifensor functions may contribute to some symptoms and complications of diabetes mellitus.

Acetylcholine↗

Non-invasive tests of neurovascular function.

This paper describes the value of non-invasive neurovascular function tests in the clinical setting. Painful transcutaneous electrical nerve stimulation (TENS) of the dorsum of the foot evoked axon reflex vasodilatation, measured by laser Doppler flowmetry. In addition, acetylcholine and sodium nitrite (NaNO2) were iontophoresed to cause vasodilatation by endothelium-dependent and -independent mechanisms, respectively. Compared with healthy volunteers, diabetic patients with clinically diagnosed neuropathy showed reduced electrical axon reflex flare responses. These responses in one additional subject were absent in a region of denervated skin. Acetylcholine responses, but not NaNO2 responses, were also depressed in patients with diabetic neuropathy. Such reduced cutaneous nocifensor functions may contribute to some symptoms and complications of diabetes mellitus.

Blood Vessels↗

Electrically evoked skin vasodilatation: a quantitative test of nociceptor function in man.

Direct stimulation of intact forearm skin affects adjacent microvascular blood flux. Pulses of current, known to activate C-fibres effectively, were applied over a period of 1-16 seconds at 2 Hz using transcutaneous stimulation. An increase of up to 50% was observed in skin microvascular blood flux. Increased blood flux correlated well with increasingly painful sensations. Some subjects responded to one or two pulses at 2 Hz, 0.5 ms in duration and 150 volts. A response onset latency of 4-15 s, lasting up to 5 minutes, was recorded. At higher frequencies (4-8 Hz) and more pulses (16-32) vasoconstriction was frequently observed before the usual flux increase. After administration of local anaesthesia (2% ligocaine) the resting skin blood flux increased, but electrical stimulation still produced vasodilatation. The local cutaneous flare response to electrical stimulation was abolished or greatly reduced by capsaicin pretreatment. Excitation of small intracutanous forearm nerve C-fibres produces increased microvascular blood flux which is dependent on local release of vasodilator substances. Thus the neurogenic flare (axon reflex) may have a physiological role in regulating skin blood flow, and nociceptor function may be measured by applying the aforementioned transcutaneous electrical stimulation.

Axons↗

Contractile properties of cat motor units enlarged by motoneurone sprouting.

The fast-twitch flexor digitorum longus (FDL) muscle was partially denervated by a unilateral section of the L7 ventral root. After approximately 100 days the isometric, force-velocity and histochemical properties of single motor units from the partially denervated muscle were determined. The diameter of the nerve axons supplying the muscle were also examined. The extrapolated maximum speed of sarcomere shortening (Vmax) of the enlarged motor units was significantly less than that of the control whole muscle Vmax. It is concluded that the motoneurone is capable of expanding its territory and therefore its tension generating capability without any apparent change in axonal diameter. In addition, the intrinsic properties of the muscle fibres are altered.

Animals↗

Motor units in cross-reinnervated fast and slow twitch muscle of the cat.

1. Isometric contractile properties of motor units were measured in cross-reinnervated fast (flexor digitorum longus) and slow (soleus) twitch muscles of the cat. All but one cross was at least 95% pure. 2. There was a reduction in the number of motor units in all muscles, but totals remained about equal in cross-reinnervated soleus and flexor digitorum longus. 3. Motor unit tensions (mean and maximum values) were higher in cross-reinnervated soleus than in cross-reinnervated flexor digitorum longus, reversing the differences between normal muscles. This was due to increases in muscle mass and in the tension developed per unit cross-sectional area. There were motor unit tensions larger and smaller than those seen in normal muscle, but the range was comparable with that seen in self-reinnervated muscle. 4. The changes in twitch time to peak of whole muscle following cross-reinnervations resulted from a change over the whole range of motor units. The conversion of soleus was less complete than that of flexor digitorum longus, and the time to peak of its fastest motor unit was twice as long as any seen in normal flexor digitorum longus. 5. In neither of the cross-reinnervated muscles were the fast contracting motor units larger than the slow contracting ones, and in cross-reinnervated soleus they were smaller. 6. Axonal conduction velocity was correlated with motor unit tension in both muscles and with twitch time to peak in cross-reinnervated flexor digitorum longus, but in all cases less clearly than in normal muscles. 7. The ratio of twitch to tetanic tension increased with increasing twitch time to peak, as in normal muscles.

Animals↗

Induced changes in the thresholds for voluntary activation of human spindle endings.

1. Recordings were made from forty-two muscle spindle afferents from the pre-tibial muscles of human subjects. For each afferent, the contraction level at which its discharge accelerated (its 'threshold for activation') was defined using isometric voluntary contractions of the receptor-bearing muscle. The effects on these thresholds of various manoeuvres designed to activate descending pathways or segmental sensory inputs were studied to determine whether the balance between the skeletomotor and fusimotor drives to the contracting muscle could be altered. 2. The Jendrassik reinforcement manoeuvre raised the threshold for voluntary activation of one spindle ending slightly but had no significant effect with seven other endings. It is concluded that the Jendrassik manoeuvre does not excite fusimotor neurons selectively or even preferentially. 3. Caloric vestibular stimulation altered the thresholds for voluntary activation of eight of eleven spindle endings, the most common effect being lowering of the threshold during the irrigation and for 1--1 . 5 min after its cessation. 4. Cutaneous stimulation by vibration lowered the thresholds for voluntary activation of some spindle endings when applied to the dorsum of the foot, and raised thresholds when applied to the lateral plantar surface. 5. Passive stretch of the receptor-bearing muscle by plantar flexion of the ankle and passive stretch of synergistic muscles in isolation raised thresholds for spindle activation; passive stretch or vibration of triceps surae lowered thresholds. 6. These studies suggest that the relationship between the skeletomotor and fusimotor drives to a muscle during a voluntary contraction is not rigidly fixed, but can be varied appropriately with the changing motor role demanded of the muscle by supraspinal drives and with the changes in sensory feed-back generated by the movement itself. 7. It is concluded that, provided the skeletomotor effects of a stimulus are known, changes in the threshold for spindle activation in a voluntary contraction can provide a means of determining the effects of that stimulus on fusimotor neurons even when the stimulus alone is not adequate to alter fusimotor drive.

Ankle Joint↗

Anticipation and fusimotor activity in preparation for a voluntary contraction.

1. Multi-unit and single-unit recordings were made of muscle spindle afferent activity from the pretibial muscles of human subjects who were initially relaxed. The muscles were subjected to a stretching perturbation of 1 s duration, occurring irregularly, on average once every 5 s. In test sequences, an auditory or visual warning was provided 1 . 06 s before some of the perturbations. Subjects were required to oppose every perturbation by contracting the receptor-bearing muscle as rapidly as possible. 2. Following the warning all subjects sometimes tensed the receptor-bearing muscle unintentionally in preparation for the perturbation. In these contractions, the discharge of a spindle ending accelerated only if the contraction strength exceeded the ending's threshold for activation, established in control voluntary contractions performed under isometric conditions. 3. When the receptor-bearing muscle did not contract in the interval between warning and perturbation, there was no detectable change in the multi-unit recordings of spindle activity or in recordings from twelve of thirteen single spindle afferents. The thirteenth spindle afferent discharged prior to the perturbation in the absence of detectable e.m.g. in response to (only) three of twenty-three warning stimuli. However, this ending had been so responsive during isometric voluntary contractions that a contraction level at which it did not respond could not be established, and it is suggested that the findings with this ending resulted from its low threshold rather than from selective activation of the fusimotor system. 4. When subjects were warned of the perturbations, the dynamic response of spindle endings to the perturbations was not increased in size or altered in latency. 5. The motor response to perturbations without warning generally contained only long-latency (volitional) e.m.g. activity occurring 107--200 ms after the onset of the perturbation. When a warning was given, short-latency (reflex) e.m.g. activity was also recorded, beginning 46--76 ms after the onset of the perturbation. 6. It is concluded that anticipation of the need to contract a muscle does not result in selective activation of fusimotor neurones in preparation for the contraction. The change in stretch reflex gain that occurs as a result of 'anticipation' occurs through a central process which does not involve the fusimotor system.

Acoustic Stimulation↗