Sine-wave auricular TENS produces frequency-dependent hypesthesia in the trigeminal nerve.

OBJECTIVE: To evaluate the effects of different frequencies of auricular (ear-to-ear) sine-wave transcutaneous electrical nerve stimulation (TENS), administered at subliminal intensity, on trigeminal nerve sensitivity. DESIGN: In a double-blind protocol, healthy volunteer subjects were administered one of three different frequencies of active TENS (5, 100, or 2,000 Hz) or placebo TENS (no current was passed) for 30 min. SETTING: Department of Psychology, City University of New York. SUBJECTS: 72 healthy undergraduate volunteers with no preexisting pain problems (16 men and 56 women), from the Department of Psychology, City University of New York. OUTCOME MEASURE: Pretreatment to posttreatment changes were measured in sensation threshold for a 250-Hz electrical stimulus applied transcutaneously to an area 1 cm anterior to the tragus of the ear (mandibular division of the trigeminal nerve). RESULTS: Analysis of variance indicated no group differences in baseline trigeminal sensation threshold, but there were significant group differences in pretreatment to posttreatment changes in sensation threshold (p < 0.001). A postiori analysis showed significant increases in trigeminal sensation threshold after active TENS as compared to placebo TENS (p < 0.05), with 5- and 100-Hz TENS producing significantly greater hypesthesia than 2,000-Hz TENS (p < 0.05). CONCLUSIONS: Sine-wave auricular TENS produces frequency-dependent trigeminal hypesthesia that is not a placebo effect.

Sensory perception in uremic patients.

Peripheral (PNS) and central (CNS) sensory nervous system function was quantitatively assessed using neuroselective transcutaneous electrical nerve stimulation (TENS) in a population of 19 chronic hemodialysis patients (ages 17-77, median 47 years; duration 1-14, median 3 years). Cutaneous current perception threshold (CPT) provided an index of PNS integrity, and a new technique involving cranial TENS to characterize cephalic evoked noncutaneous sensations (CENS) was used to assess CNS sensory function. Patients showed both CPT (32%) and CENS (89%) abnormalities as compared with previously tested healthy subjects. No significant correlation was observed between age, duration of dialysis, PNS, and CNS abnormalities. The CPT examination provides a sensitive and easy to administer test of PNS sensory function for the purpose of assessing the adequacy of dialysis in chronic hemodialysis patients; the CENS examination also may prove useful in this regard.

Current perception threshold screening for carpal tunnel syndrome.

Screening for the onset of carpal tunnel syndrome (CTS), which is associated with excess ergonomic stresses of the wrist and hand, is a major concern in occupational medicine. CTS questionnaires, physical examinations, and quantitative sensory function determination through neuroselective current perception threshold (CPT) measurements were obtained from the median digital nerves of 16 assembly line workers who were symptomatic with hand pain. Median nerve evaluations by CPT detected sensory abnormalities in 75% of the workers, and abnormalities in 50% of the workers were detected by clinical evaluations (p less than .05, df = 22). CPT abnormalities were characterized as "hypoesthetic" in 25% and hyperesthesic in 42% of the workers. The noninvasive, nonaversive CPT technique provided sensitive and easily obtained quantitative measures. Regular use of this procedure in the occupational setting may assist in preventing the development of advanced CTS for it provides early detection of median nerve abnormalities.

Effects of cranial transcutaneous electrical nerve stimulation in normal subjects at rest and during psychological stress.

Some effects of sub-threshold sine-wave transcutaneous electrical nerve stimulation (TENS), passed between earlobe electrodes at a constant alternating current (AC) frequency of 100 Hertz (Hz), were investigated in 90 normal subjects after 30 minutes of treatment, and after 3 minutes of standardized mental stress (mental arithmetic) which immediately followed the 30 minute treatment. In a double-blind protocol, five groups received 1) active TENS during treatment and active TENS during stress; 2) active TENS during treatment and placebo TENS during stress; 3) placebo TENS during treatment and placebo TENS during stress; 4) placebo TENS during treatment and active TENS during stress; and 5) no treatment during both treatment and stress. Results showed significant reductions in systolic blood pressure, pulse rate and anxiety, but not in diastolic blood pressure or peripheral vascular tension, after 30 minutes of active TENS as compared to no treatment. No placebo TENS effect was observed. No significant differences were observed between active TENS; placebo TENS and no treatment in physiological or psychological response to the stress procedure. Results are discussed in terms of the applicability of this technique to the management of stress.

Mapping diabetic sensory neuropathy by current perception threshold testing.

Detailed clinical neurological examinations were conducted on 44 nondiabetic volunteers and 59 diabetic subjects. The examinations focused particularly on sensory symptomatic and physical evaluation. Standardized assessment of symptoms and physical testing of light touch, pain, vibratory, and thermal sensation was performed at the hand, wrist, elbow, foot, ankle, and knee. A total symptom score and physical score were defined by summing test scores at each site. Current perception threshold (CPT) testing that used constant sine-wave-alternating current was conducted at the same anatomic sites. CPT correlations with the physical score gave r values of .55 for 5 Hz, .60 for 250 Hz, and .62 for 2000 Hz (n = 618). Correlations with the symptom score were not as strong: r = .45 for 5 Hz, .46 for 250 Hz, and .51 for 2000 Hz. The correlation with symptom score was due primarily to a strong relationship for the symptom of numbness (r = .53 for all 3 frequencies). Correlations with pain and paresthesia were much lower. CPTs for diabetic subjects at the three frequencies were higher at most locations than for the nondiabetic volunteers. However, CPTs were no different from normal values in diabetic subjects without evidence of neuropathy. CPT testing appears to be a useful technique for assessment of diabetic sensory neuropathy.

Current perception threshold. Reproducibility and comparison with nerve conduction in evaluation of carpal tunnel syndrome.

Neuro-selective current perception threshold (CPT) values quantify peripheral nerve (n) integrity and provide an index of adequate hemodialysis (HD). Evaluation of polyneuropathy (PN) by CPT correlates with nerve conduction testing (NCT). CPT is convenient, painless, and may be performed during HD. Early detection of carpal tunnel syndrome (CTS), a complication of uremia, permits curative intervention. Utility of CPT and NCT measurements in detecting CTS in 29 stable HD patients were evaluated. Reproducibility of seven CPT determinations over 4 weeks was determined in each of 9 HD patients. The coefficient of variation for repeated 2000 Hz CPT measures was 6%. PN was detected by CPT in 92% of the patients and by NCT in 79% (r = 0.79, p less than 0.001). In 38% of the hands there was a CPT impairment in both the median and ulnar nerves (n), of which 25% were symptomatic for CTS. CPTs consistent with CTS (sufficiently greater impairment of the median vs ulnar n) were observed in 31% of the hands with combined median and ulnar n CPT abnormalities, and 11% were identified with CTS by NCT. The unique ability of the CPT exam to quantify hyperesthesia may account for its superior CTS detection sensitivity. These findings demonstrate that repeated CPT determinations are consistent and are diagnostic for CTS.

A comparison of nerve conduction velocities and current perception thresholds as correlates of clinical severity of diabetic sensory neuropathy.

Nerve conduction velocities (NCVs) are the standard measurements used to confirm the presence or absence of diabetic neuropathy. NCVs were contrasted with the newer technique of measurement of alternating current perception thresholds (CPTs) in assessing the quantitative level of correlation with severity of diabetic sensory neuropathy. A very detailed, scored neurological history (symptoms) and physical examination, emphasising sensory assessment, was conducted on 71 individuals with diabetic neuropathy of varying degrees of severity. Sensory and motor NCVs and CPTs at 5, 250, and 2000 Hz of the upper and lower extremities were determined for these individuals. In addition, vibration thresholds (VTs) were measured as a third modality. Twenty eight individuals underwent repeated evaluations at 2, 6, 10 and 12 months after the initial procedures. Using the results of 169 complete evaluations, correlations were determined between physical scores (PS) and symptoms scores (SS) and NCVs. NCV correlations with the SS were weaker than with the PS. The strongest of the correlations were found between the PS and motor NCVs of the median nerve (rho = 0.29) and the tibial nerve (rho = 0.38). Normal NCVs were present in the face of very significant historical and physical abnormality. Correlations of the SS and PS with both VTs and CPTs were higher than with the NCVs. CPTs proved the more effective as predictors of both symptomatic and physical impairment. NCVs appear to lack the resolving power necessary to evaluate subtle differences in clinical state of diabetic sensory neuropathy. The supplementary use of current perception testing may improve the quantitative assessment of this condition.

The effects of cranial TENS on measures of autonomic somatic and cognitive activity.

Peripheral and central nervous system effects of the cranial application of sub-threshold transcutaneous electrical nerve stimulation (TENS), of sinusoid waveform passed between earlobe electrodes at an AC frequency of 100 Hertz, were investigated. In a single-blind study, each of thirty healthy volunteer subjects was administered one 30 minute treatment of either active TENS, placebo TENS or no treatment. Pretreatment to post-treatment changes in measures of autonomic activity (blood pressure, pulse rate, peripheral vasomotor activity), somatic activity (skeletal muscle tension), and anxiety were evaluated. Significant reductions in systolic blood pressure (p less than .05), diastolic blood pressure (p less than .01), pulse rate (p less than .05), peripheral vasomotor activity (marginally significant: p less than .07) and anxiety (p less than .05) were observed subsequent to active. TENS as compared to both placebo TENS and no TENS. No significant placebo TENS effect was observed. Possible mechanisms of action of this form of cranial TENS on the peripheral and central nervous system are discussed.

Neuropathy of uremia: evaluation by nerve conduction velocity versus neurospecific current perception threshold.

Normal peripheral nerve conduction is a marker of adequate dialytic therapy in the ESRD population. Decreasing nerve function detected by periodic testing indicates insufficient dialysis. The standard test for the quantitative evaluation of nerve integrity is the nerve conduction test (NCT). A study of 34 dialysis patients proves that the measurement of current perception threshold (CPT) is equally effective to NCT in defining peripheral nerve function (r = 0.81; p less than 0.001). The superiority of the CPT examination is discussed.

Current perception: preferred test for evaluation of peripheral nerve integrity.

While other parameters of dialysis may reflect acute events or lack specificity, assessment of peripheral nerve function remains a dependable indicator of the adequacy of high flux and rapid hemodialysis (HD). The nerve conduction test (NCT) is an accurate neurometric technique that is hampered by low patient compliance. This report examines the current perception threshold (CPT) test as a reliable alternative neurometric procedure to the NCT. The reliability of the CPT test was established in a one year longitudinal evaluation of 23 HD patients. CPT and NCT tests were performed on the median and peroneal nerves, bilaterally, with correlations of r = 0.83 for the initial determination and r = 0.80 one year later (P less than 0.001). CPT was shown to be a superior technique to NCT, as it is quick (tested during HD) and painless.

Constant current sine wave transcutaneous nerve stimulation for the evaluation of peripheral neuropathy.

We have evaluated various forms of peripheral neuropathy with a new device which emits a constant sinusoid stimulus at varying frequencies to quantitate current perception thresholds (CPTs). In normal individuals, CPT measures increase with increasing stimulation frequency, are highest on the toe and lowest on the face. There is a significant effect of age and sex on threshold perception. In patients with neuropathy, there is a marked increase in thresholds on hands and feet, as well as a lesser but still significant increase of facial CPTs. Thresholds furthermore correlated with clinical severity in a group of patients with diabetic neuropathy. Facial thresholds were markedly elevated in the patients with moderate to severe neuropathy, suggesting that the device is sensitive to the systemic nature of peripheral neuropathy. The authors believe the device will be a useful tool in screening for sensory neurologic abnormalities.

New screening device for assessment of peripheral neuropathy.

Screening for the onset of toxic and entrapment neuropathy is a major concern in occupational medicine today. Current perception thresholds may be used as a measure of the integrity of the peripheral nervous system. A new transcutaneous nerve stimulator was used to evaluate current perception thresholds in 54 normal persons and 33 diabetic subjects. Current perception thresholds in the normal volunteers with no evidence of peripheral neuropathy were found to vary significantly with the frequency and location of the stimulation, as well as age. The test identified the diabetic peripheral neuropathy with an overall sensitivity of 94%. This new diagnostic technique is quick, simple to perform, noninvasive and nonaversive and provides a sensitive quantitative measure of sensory function. This diagnostic stimulator will be useful for screening occupationally related toxic and entrapment neuropathies in which sensory impairment is an early finding.

Transcutaneous nerve stimulation. Frequency and waveform specificity in humans.

The effects of transcutaneous electrical nerve stimulation (TNS) of a constant alternating current administered at various frequencies and waveforms to volunteer human subjects were investigated. The TNS was found to evoke noncutaneous subjective sensations in all the subjects. Only with a sinusoid waveform of TNS were distinct frequency ranges of the stimulation associated with specific noncutaneous subjective sensations. Our findings suggest that nervous tissue is capable of discriminating the waveform parameters of an electrical stimulus.

Adenosine receptor interactions and anxiolytics.

[3H]-N6-cyclohexyladenosine and [3H]-1,3-diethyl-8-phenylxanthine label the A1 subtype of adenosine receptor in brain membranes. The affinities of methylxanthines in competing for A1 adenosine receptors parallel their potencies as locomotor stimulants. The adenosine agonist N6-(phenylisopropyl) adenosine is a potent locomotor depressant. Both diazepam and N6-(L-phenylisopropyl)adenosine cause locomotor stimulation in a narrow range of subdepressant doses. Combined stimulant doses of the two agents depress motor activity, as do larger doses of either one, given separately. Evidence supporting and against the hypothesis that some of the actions of benzodiazepines are mediated via the adenosine system is reviewed. A number of compounds interact with both systems, probably because of physico-chemical similarities between adenosine and diazepam. It is concluded that of the four classic actions of benzodiazepines, the sedative and muscle relaxant (but not anxiolytic or anticonvulsant) actions could possibly be mediated by adenosine.

Interactions in the behavioral effects of methylxanthines and adenosine derivatives.

The role of adenosine receptors in behavioral effects of alkylxanthines was evaluated in mice. The relative potencies of alkylxanthines in reversing locomotor activity depression elicited by L-phenylisopropyladenosine (L-PIA) were similar to relative potencies in competing for adenosine receptors labeled by [3H]cyclohexyladenosine. Whereas L-PIA at i.p. doses of 0.10 mumol/kg and higher depressed locomotor activity, lower doses (0.01 and 0.05 mumol/kg) augmented locomotor activity. At the doses evaluated, caffeine did not further augment the L-PIA (0.05 mumol/kg)-enhanced locomotor activity. Low doses of diazepam, like L-PIA, augmented locomotor activity. Combining locomotor depressant doses of diazepam and caffeine produced a paradoxical stimulation of activity, as observed also for L-PIA and caffeine. Low doses of diazepam but not L-PIA increased crossings between the light and dark sites in a shuttle box, indicating a difference in the behavioral profile of these two agents. At behaviorally effective doses, L-PIA did not alter blood pressure or heart rate, but elicited some premature ventricular contractions which, however, occurred to a similar extent at locomotor depressant and stimulant doses of L-PIA. Brain levels of L-PIA at the lowest behaviorally active doses were adequate to occupy more than 50% of adenosine receptors. Thus, the behavioral effects of L-PIA appeared to be mediated in the brain and were not secondary to the cardiovascular effects.

Adenosine receptors and behavioral actions of methylxanthines.

Central stimulant actions of 10 methylxanthines in mice correlate with affinities for adenosine receptors labeled with N6-[3H]cyclohexyladenosine. Affinities of methylxanthines for adenosine receptors are consonant with central levels attained at behaviorally effective doses. The much higher concentrations of methylxanthines required to influence benzodiazepine receptor binding do not correlate with behavioral potency. N6-(L-Phenylisopropyl)adenosine (L-PIA), a metabolically stable analog of adenosine with high affinity for adenosine receptors, is an extremely potent behavioral depressant, reducing locomotor activity of mice at doses as little as 0.05 mumol/kg. The D isomer, which has much less affinity for adenosine receptors, is much less active as a central depressant. Theophylline stimulates locomotor activity and reverses depressant effects of L-PIA. Caffeine or 1,7-dimethylxanthine, when administered alone, elicits biphasic effects, with locomotor depression at lower doses and stimulation at higher doses. When administered with L-PIA, even low doses of caffeine produce marked stimulation. 3-Isobutyl-1-methylxanthine given alone elicits only behavioral depression. However, like theophylline and caffeine, isobutylmethylxanthine reverses the L-PIA-evoked depression, converting it into pronounced locomotor stimulation. The data strongly suggest that the behavioral stimulant effects of methylxanthines involve a blockade of central adenosine receptors.