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Auditory evoked potentials in cats with neonatal high frequency hearing loss. Evidence of abnormal frequency representation in the midbrain.

We have recorded auditory evoked potentials, of both neurogenic and myogenic origin, in cats having neonatal high frequency cochlear hearing loss. Using frequency specific stimuli (tone pips) and by measuring responses near to threshold, we have probed tonotopic (or cochleotopic) representation within the brainstem-midbrain auditory pathway. At stimulus frequencies corresponding to the high frequency cut-off of the cats' audiograms we have observed enhanced amplitudes of both auditory brainstem evoked responses (ABR) and postauricular myogenic (PAM) potentials. We interpret our findings as evidence of a larger than normal population of neurons tuned to this frequency region. We suggest that such abnormal frequency representation results from a long-term sensory deficit caused by lesions to the basal, high frequency region of the cochleas.

Animals↗

High-frequency hearing influences lower-frequency distortion-product otoacoustic emissions.

OBJECTIVES: The primary goal of this study was to test the ability of 2f1-f2 distortion-product otoacoustic emissions (DPOAEs) to detect reduced cochlear function in the presence of normal behavioral sensitivity. DESIGN: A prospective study was performed in normal-hearing young adults using simple and complex regression analyses to clarify the relationship between ultra-high frequency (UHF) hearing and DPOAE levels at lower frequencies, as well as the influence of hearing levels for frequencies within the conventional test range and subject age on this association. METHODS: Average DPOAE levels between 4 to 8 kHz, which were elicited by equilevel primary tones of low to moderate levels, were measured as level-frequency functions, or distortion-product (DP) grams, and related to the mean UHF hearing levels from 11.2 to 20 kHz. The median hearing level for the UHF hearing was used to separate subjects into good and poor UHF hearers. This distinction was then used to compare DPOAE levels from 4 to 8 kHz for the 2 groups to determine if UHF hearing status influenced DPOAE levels at lower frequencies. RESULTS: Simple regression analysis revealed that the 4-to 8-kHz DPOAE levels were significantly correlated with the pure-tone average (PTA) from 11.2 to 20 kHz. However, the PTA for 4 and 8 kHz was also significantly correlated with the PTA for UHF hearing. Further multiple regression analyses revealed that UHF hearing significantly and uniquely accounted for approximately 14% of the variance in DPOAE levels from 4 to 8 kHz for most of the primary-tone level combinations. In contrast, neither the PTA for the conventional hearing range nor subject age contributed significantly to the DPOAE variance. CONCLUSIONS: The findings suggest that UHF hearing influences DPOAEs at significantly lower frequencies because emissions are sensitive to subtle changes in outer hair cells not yet detected by pure-tone thresholds in this region or because alterations in the basal cochlea affect the generation of lower-frequency DPOAEs originating from more apical cochlear regions.

Adolescent↗

Micronucleated erythrocyte frequencies in old and new world primates: measurement of micronucleated erythrocyte frequencies in peripheral blood of Callithrix jacchus as a model for evaluating genotoxicity in primates.

Nonhuman primates are of particular relevance in evaluating the potential toxicity of drugs and environmental agents. We have used previously published information and data from the present study to establish a relationship for New World (NW) and Old World (OW) primates on the basis of the frequency of spontaneous micronucleated erythrocytes (MNEs) observed in peripheral blood. Data on spontaneous MNEs in peripheral blood from 15 species of primates, including humans, indicate that NW primates have significantly (P < 0.01) higher MNE frequencies (group mean, 9.5 +/- 7.3 MNEs/10,000 erythrocytes; range, 0.7-20.5/10,000 erythrocytes) than OW primates (group mean, 1.0 +/- 0.9 MNEs/10,000 erythrocytes; range, 0.0-2.6 MNEs/10,000 erythrocytes). Humans are believed to have developed in the OW, and human MNE frequencies were similar to those described for OW primate species. We selected the common marmoset (Callithrix jacchus), a NW primate, to determine whether therapeutic pediatric doses of Metotrexate (MTX; 2.5 mg/kg), Cyclophosphamide (CP; 5 mg/kg), Cytosine-arabinoside (Ara-C; 3 mg/kg), or 5-Fluorouracil (5-FU; 10 mg/kg), administered daily for two consecutive days, increase the frequency of micronuclei. Micronucleated polychromatic erythrocyte frequencies were increased significantly in groups receiving MTX, CP and Ara-C, while MNE frequencies were increased by the Ara-C treatment. The results of this study indicate that NW primates have higher spontaneous MNE frequencies than OW primates, and because of this, NW primates like the common marmoset, may be suitable for evaluating the genotoxicity of chemical agents.

Animals↗

Frequency dependence and gender effects in visual cortical regions involved in temporal frequency dependent pattern processing.

Neural response to flickering stimuli has been shown to be frequency dependent in the primary visual cortex. Controversial gender differences in blood oxygen level dependent (BOLD) amplitude upon 6 and 8 Hz visual stimulation have been reported. In order to analyze frequency and gender effects in early visual processing we employed a passive graded task paradigm with a dartboard stimulus combining eight temporal frequencies from 0 to 22 Hz in one run. Activation maps were calculated within Statistical Parametric Mapping, and BOLD amplitudes were estimated for each frequency within the striate and extrastriate visual cortex. The BOLD amplitude was found to steadily rise up to 8 Hz in BA 17 and 18 with an activation plateau at higher frequencies. In addition, we observed a laterality effect in the striate cortex with higher BOLD contrasts in the right hemisphere in men and in women. BOLD response rises similarly in men and women up to 8 Hz but with lower amplitudes in women at 4, 8, and 12 Hz (30% lower). No frequency effect above 1 Hz was found in the extrastriate visual cortex. There was also a regional specific gender difference. Men activated more in the right lingual gyrus (BA 18) and the right cerebellum compared with women, whereas women showed more activation in the right inferior temporal gyrus (BA 17). The study indicates that frequency dependent processing at the cortical level is limited to the striate cortex and may be associated with a more global information processing (right hemisphere dominance), particularly in men. The finding of significantly lower BOLD amplitudes in women despite previously shown larger VEP (visual evoked potential) amplitudes might suggest gender differences in cerebral hemodynamics (baseline rCBV, rCBF, or neurovascular coupling). The regional distinction points at additional differences in psychological processing even when using a simple visual stimulus.

Adult↗

Frequency and space representation in the primary auditory cortex of the frequency modulating bat Eptesicus fuscus.

1. Frequency and space representation in the auditory cortex of the big brown bat, Eptesicus fuscus, were studied by recording responses of 223 neurons to acoustic stimuli presented in the bat's frontal auditory space. 2. The majority of the auditory cortical neurons were recorded at a depth of less than 500 microns with a response latency between 8 and 20 ms. They generally discharged phasically and had nonmonotonic intensity-rate functions. The minimum threshold, (MT) of these neurons was between 8 and 82 dB sound pressure level (SPL). Half of the cortical neurons showed spontaneous activity. All 55 threshold curves are V-shaped and can be described as broad, intermediate, or narrow. 3. Auditory cortical neurons are tonotopically organized along the anteroposterior axis of the auditory cortex. High-frequency-sensitive neurons are located anteriorly and low-frequency-sensitive neurons posteriorly. An overwhelming majority of neurons were sensitive to a frequency range between 30 and 75 kHz. 4. When a sound was delivered from the response center of a neuron on the bat's frontal auditory space, the neuron had its lowest MT. When the stimulus amplitude was increased above the MT, the neuron responded to sound delivered within a defined spatial area. The response center was not always at the geometric center of the spatial response area. The latter also expanded with stimulus amplitude. High-frequency-sensitive neurons tended to have smaller spatial response areas than low-frequency-sensitive neurons. 5. Response centers of all 223 neurons were located between 0 degrees and 50 degrees in azimuth, 2 degrees up and 25 degrees down in elevation of the contralateral frontal auditory space. Response centers of auditory cortical neurons tended to move toward the midline and slightly downward with increasing best frequency. 6. Auditory space representation appears to be systematically arranged according to the tonotopic axis of the auditory cortex. Thus, the lateral space is represented posteriorly and the middle space anteriorly. Space representation, however, is less systematic in the vertical direction. 7. Auditory cortical neurons are columnarly organized. Thus, the BFs, MTs, threshold curves, azimuthal location of response centers, and auditory spatial response areas of neurons sequentially isolated from an orthogonal electrode penetration are similar.

Acoustic Stimulation↗

Frequency tuning, latencies, and responses to frequency-modulated sweeps in the inferior colliculus of the echolocating bat, Eptesicus fuscus.

Neurons in the inferior colliculus (IC) of the awake big brown bat, Eptesicus fuscus, were examined for joint frequency and latency response properties which could register the timing of the bat's frequency-modulated (FM) biosonar echoes. Best frequencies (BFs) range from 10 kHz to 100 kHz with 50% tuning widths mostly from 1 kHz to 8 kHz. Neurons respond with one discharge per 2-ms tone burst or FM stimulus at a characteristic latency in the range of 3-45 ms, with latency variability (SD) of 50 microseconds to 4-6 ms or more. BF distribution is related to biosonar signal structure. As observed previously, on a linear frequency scale BFs appear biased to lower frequencies, with 20-40 kHz overrepresented. However, on a hyperbolic frequency (linear period) scale BFs appear more uniformly distributed, with little overrepresentation. The cumulative proportion of BFs in FM1 and FM2 bands reconstructs a scaled version of the spectrogram of FM broadcasts. Correcting FM latencies for absolute BF latencies and BF time-in-sweep reveals a subset of IC cells which respond dynamically to the timing of their BFs in FM sweeps. Behaviorally, Eptesicus perceives echo delay and phase with microsecond or even submicrosecond accuracy and resolution, but even with use of phase-locked FM and tone-burst stimuli the cell-by-cell precision of IC time-frequency registration seems inadequate by itself to account for the temporal acuity exhibited by the bat.

Animals↗

Effect of spatial frequency of stimulus on focal macular ERGs in monkeys : fmacERG dependence on the spatial-frequency.

PURPOSE: To determine the effect of the spatial frequency of a small grating stimulus centered on the macula on the focal macular ERGs (fmacERGs) of monkeys. METHODS: fmacERGs were recorded from eight eyes of four adult monkeys (Macaca fuscata). The spatial frequency of the stimulus was changed from 0.25 to 8 cycles/degree. The luminance of the light bars was 10 cd/m(2), and the contrast was 95%. The stimulus was flashed on and off with an on duration of 100 ms and an off duration of 150 ms (4 Hz). The stimulus was centered on the fovea and subtended 12.7 degrees at the cornea. The luminance of the steady light-adapting background was 3.5 cd/m(2). The location of the stimulus on the retina was monitored throughout the recordings. The effects of the spatial frequency of the stimulus on the amplitudes and implicit times of the a-waves, b-waves, and oscillatory potentials (OPs) were determined. fmacERGs were also recorded following intravitreal tetrodotoxin (TTX). RESULTS: The amplitudes of the a- and b-waves did not change with changes in the spatial frequency of the stimulus. The OPs, on the other hand, responded best to the lowest spatial frequency, and the OPs after the first two were attenuated at intermediate and higher frequencies (Wilcoxon signed-rank test: P < 0.05). TTX reduced all OP wavelets in monkeys. CONCLUSIONS: The OPs of the photopic macular ERGs are affected by the spatial frequency of the stimulus and are reduced by TTX, consistent with their being generated by inner retinal neurons.

Adaptation, Ocular↗

In vivo mutant T cell frequency in atomic bomb survivors carrying outlying values of chromosome aberration frequencies.

Frequencies of HPRT- mutant T cells were determined by means of a direct clonal assay in atomic bomb survivors who showed outlying values of chromosome aberration frequencies. The studied survivors consisted of 2 groups: those whose aberration frequency was near the higher end of the distribution (high-aberration group) and those whose aberration frequency was near the lower end of the distribution (low-aberration group). The mean radiation doses (T65D) of the high-aberration group (13 people) and low-aberration group (17 people) were 248 and 273 rad, respectively. The mean mutant frequency (Mf) of the high-aberration group was 6.7 X 10(-6), which was significantly higher than that of the low-aberration group (3.7 X 10(-6)) or that of 17 controls (3.4 X 10(-6)). When all the samples were combined, the correlation between Mf and radiation dose was not significant using either dose estimation system, T65D or DS86. However, the correlation coefficient was higher when DS86 doses were used. Mf correlated significantly with increasing aberration frequencies. The tendency that Mf correlates better with chromosome aberration frequency than with estimated radiation dose was stronger in this study than in a previous study where the samples were selected randomly.

Chromosome Aberrations↗

Frequency dependence of dead space during high-frequency ventilation in dogs.

A rotary valve ventilator, designed to allow the direct measurement of expired gas volume and composition, was used to maintain gas exchange in anesthetized, paralyzed, mongrel dogs at ventilatory frequencies up to 20 Hz. A total of eleven studies were carried out on four animals. Determinations of the minute ventilation required to maintain a normal steady-state PCO2, together with the FECO2 and arterial PO2, PCO2, and pH, were made at a number of frequencies. The results so obtained were used to calculate the Bohr (physiological) dead space. Dead space remained approximately constant at close to the value measured during spontaneous ventilation for each individual dog in the range of ventilatory frequencies from below 1 to around 5 Hz, but decreased with increasing frequency above 5 Hz. The calculated physiological dead space at 15 Hz was about half of the value at normal respiratory frequencies. These findings in dogs, obtained using a ventilator system which allows very accurate determinations of expired gas volume and content, are consistent with published results for this species from other laboratories. They contrast with our earlier findings in rabbits that dead space remains constant with increasing frequency, suggesting that the effects of high-frequency ventilation on CO2 transport are species-dependent.

Animals↗

Frequency modulation of neuronal theta-bursts in rabbit's septum by low-frequency repetitive stimulation of the afferent pathways.

Activity of the neurons with stable theta-bursts was recorded extracellularly in intact and hippocampectomized septum of unanesthetized chronic rabbits during low-frequency (3-17 Hz) stimulation of horizontal limb of diagonal band or lateral septal nucleus. The stimulation rarely evoked standard oligosynaptic single-spike responses in stable theta-bursting units. Instead, gradual entrainment and phase-locking of the spontaneous theta-cycles occurred. Two types of entrainment were observed: "entrainment by the pause", where interburst interval was reset by the stimuli; and "entrainment by the burst", where bursts were time-locked to the stimuli. Such reorganization of the spontaneous bursts occurred in the narrow frequency range of stimulation (from 4 Hz up to 9-12 Hz), with the best resonance following in the range of "basic" theta frequencies of the awake rabbit (5-6 Hz). With stimulation beyond the theta-range three phenomena occurred: shift of the burst frequencies to higher or lower harmonics of stimulation frequencies; complex interactions of basic background frequency with rhythm of stimulation ("beating"); return to background theta-burst frequency in spite of continuing stimulation ("escape"). The properties of the septal theta-bursting cells as presumable intrinsic bursting pacemakers are discussed.

Afferent Pathways↗

Temporal effects in simultaneous pure-tone masking: effects of signal frequency, masker/signal frequency ratio, and masker level.

The effect of the temporal relationship between a pure-tone masker and a pure-tone signal in simultaneous masking was investigated in three experiments. The experiments extend previous work by: studying the temporal effect over a wide range of signal frequencies, studying the change in masking over time for several masker/signal frequency ratios, and studying the growth of masking for a brief signal at different temporal positions within a longer duration masker. In the first experiment, threshold was measured for a 20-ms signal temporally centered in a masker whose duration ranged from 20 ms to continuous. Signal frequency (fs) was 0.5, 1.0, 2.0, 4.0, or 8.0 kHz; masker frequency (fm) was 1.2 fs. For all signal frequencies, the amount of masking decreased as masker duration increased. In the second experiment, threshold was measured for a 20-ms, 1.0-kHz signal as a function of the signal's temporal position within a 400-ms masker whose frequency ranged from 1.0 to 1.25 kHz. For all but the 1.0-kHz masker, for which threshold was almost independent of the signal's temporal position, threshold decreased as signal onset was delayed relative to masker onset, but then increased slightly as the signal approached masker offset. In the final experiment, growth-of-masking functions were measured for a 20-ms, 1.0-kHz signal positioned at the beginning, at the temporal center, or at the end of a 400-ms masker whose frequency was 1.20 or 1.25 kHz. The masking functions generally were steepest for a signal at the onset of the masker and, for a given temporal position, steepest for the 1.20-kHz masker.

Adaptation, Physiological↗

[Pathophysiological mechanisms implicated by high-frequency stimulation in Parkinson's disease: the restoration of high and low frequency oscillatory systems].

INTRODUCTION: Increased neuronal activity in the internal pallidum (GPi) and the subthalamic nucleus (STN) has been clearly demonstrated in Parkinsonian models, and the two structures have thus been selected as therapeutic targets for functional neurosurgery. High-frequency electrical stimulation of the GPi or the STN improves the parkinsonian symptoms but also dyskinesias directly by GPi stimulation or indirectly by reduction of L-Dopa associated with STN stimulation. According to Alexander's model of the organisation of the basal ganglia, electrical stimulation of GPi or STN should have led to uncontrolled hyperkinesia. This apparent paradox could be explained on one hand by the involvement of different anatomo-functional areas within these structures and on the other by spatial and temporal changes in neuronal discharge patterns in the basal ganglia which in turn produce variations in synchronisation. RESULTS: Event-related (de)synchronisation (ERD) has enabled us to study variations in subcortico-cortical oscillatory activity: it has been shown that high-frequency electrical stimulation of the GPi/STN increases desynchronisation of low frequency rhythms (mu and beta,<30 Hz) during movement preparation and execution and augments post-movement synchronisation. Stimulation also decreases the abnormal frontocentral spreading of desynchronisation during movement preparation. CONCLUSIONS: In accordance with previous coherence analyses, electrical stimulation of STN is likely to restore the activity of high-frequency and low-frequency systems, as evidenced by a decrease in the hypersynchronisation of low-frequency rhythms at rest and restoral of a high-frequency rhythm during movement. Stimulation may improve spatial selectivity by activating the selected programs in conjunction with the primary sensorimotor cortex, whilst inhibiting competitive programs represented by abnormal spreading outside the primary sensorimotor cortex.

Basal Ganglia↗

Cochlear and fast electrical responses to frequency modulated tones: a frequency specific stimulus.

Some characteristics of "the fast response" to frequency modulation were explored here by examining (1) CM and AP in animal experiment and (2) BER in human study. CM to frequency modulated tone showed frequency change and amplitude change, the latter of which is probably due to frequency characteristics of the sound conductive system of the ear. Compared with AP to tone burst, latency and amplitude of AP to FM tone depends less on stimulus intensity. AP to FM tone is suspected to be a result of new excitement of the restricted area stimulated by shifted frequency. The result of analysis on human BER is well consistent with the result of AP study in animal experiment, and latency curves of BER were to some extent linear to a log scale of shifted frequencies. Thus, FM tone is possibly a frequency specific stimulus.

Acoustic Stimulation↗

Effect of myocardial hypertrophy on systolic and diastolic function in children: insights from the force-frequency and relaxation-frequency relationships.

OBJECTIVE: The objective of this study was to evaluate the effect of myocardial hypertrophy on systolic and diastolic properties of the left ventricle in children. BACKGROUND: In children with myocardial hypertrophy, ejection phase indices are invariably increased. However, indices of force-generation, e.g., end-systolic elastance and invasive indices of diastolic properties, have been studied infrequently in children with myocardial hypertrophy. METHODS: We studied 10 children with congenital aortic stenosis or coarctation of aorta and nine control patients. Systolic properties were assessed from shortening fraction, end-systolic fiber elastance (Ef(es)) measured at resting heart rates, and force-frequency relationship measured at heart rates increasing from 110 to 160 beats per minute. Diastolic properties were assessed from time constant of relaxation (tau) at matched heart rates, chamber stiffness constant, myocardial stiffness constant, and relaxation-frequency relationship measured at gradually increasing heart rates. RESULTS: Ef(es) remained unchanged by myocardial hypertrophy, however, tau was prolonged (tauL: 27.3+/-2.3 vs. 21.8+/-2.2 ms, p < 0.001; and tauD: 43.2+/-3.1 vs. 34.3+/-3.3 ms, p < 0.001). Both chamber and myocardial stiffness constants remained unchanged. Incremental increases in heart rate produced incremental improvement in both contraction and relaxation. Slopes of force-frequency and relaxation-frequency relationships remained unchanged in the experimental group. However, the relaxation-frequency relationship manifested a parallel shift upward. CONCLUSIONS: In conscious, sedated children with myocardial hypertrophy, systolic function assessed by an index of force generation remains unchanged. However, relaxation is prolonged but passive diastolic properties remain unaffected. The combined effect of hypertrophy and heart rate does not alter the force-frequency and relaxation-frequency relationships.

Aortic Coarctation↗

A theoretical analysis of low-frequency sonophoresis: dependence of transdermal transport pathways on frequency and energy density.

PURPOSE: Application of low-frequency ultrasound has been shown to increase skin permeability, thereby facilitating delivery of macromolecules (low-frequency sonophoresis). In this study, we seek to determine the dependence of transport pathways during low-frequency sonophoresis on ultrasound parameters. METHODS: Pig skin is exposed to low-frequency ultrasound over a range of frequencies to achieve different skin resistivities. The porous pathway model is used to study the dependence of average pore size, porosity, and tortuosity on ultrasound parameters. Imaging experiments are also carried out to visualize the transport pathways created by ultrasound. RESULTS: The data show that the average pore size, determined from the porous pathway model, does not depend on application frequency. Both in the presence and absence of ultrasound the average pore size determined from mannitol delivery is the same (28 +/- 12 A). With the application of ultrasound the skin porosity could be increased by up to 1700-fold. The effect of ultrasound on skin is heterogeneous thereby creating localized transport pathways (LTP). The porosity of these transport pathways is of the same order of magnitude as that of the dermis. CONCLUSIONS: With this study it is shown that low-frequency ultrasound increases skin permeability by increasing skin porosity rather than by increasing the size of the pores that are responsible for permeant delivery.

Administration, Cutaneous↗

Resonance frequency measurements of implant stability in vivo. A cross-sectional and longitudinal study of resonance frequency measurements on implants in the edentulous and partially dentate maxilla.

The aim of this investigation was to evaluate the use of resonance frequency measurements in the clinical measurement of implant stability. Resonance frequency measurements are undertaken by measuring the response of a small transducer attached to an implant fixture or abutment. Two groups of patients were selected for study. Group A comprised 9 patients who had a total of 56 implants placed. Resonance frequency measurements were made at fixture installation and repeated 8 months later at abutment connection. The resonance frequency of the implant/transducer system increased for 50 out of the 56 implants from a mean value of 7473 Hz +/- 127 Hz (P < 0.05) to a mean of 7915 Hz +/- 112 Hz (P < 0.05). Two implants had failed to integrate and the resonance frequency of these had fallen. Group B comprised 9 patients who had been provided with fixed prostheses and had a total of 52 implants placed. They were examined 5 years after fixture placement and the prostheses removed. All implants were judged clinically to be osseointegrated. The level of the marginal bone around each implant was calculated by measuring the number of exposed threads on intraoral periapical radiographs and added to the length of each abutment to give a value termed the effective implant length (EIL). Measurements indicated a correlation (R = -0.78, P < 0.01) between EIL and resonance frequency. The results support the hypothesis that the resonance frequency of an implant/transducer system is related to the height of the implant not surrounded by bone and the stability of the implant/tissue interface as determined by the absence of clinical mobility.

Aged↗

Modeling the effects of repetitions, similarity, and normative word frequency on old-new recognition and judgments of frequency.

Judgments of frequency for targets (old items) and foils (similar; dissimilar) steadily increase as the number of times a target is studied increases, but discrimination of targets from similar foils does not steadily improve, a phenomenon termed registration without learning (D. L. Hintzman & T. Curran, 1995; D. L. Hintzman, T. Curran, & B. Oppy, 1992). The present experiment explores this phenomenon with words of differing normative word frequency. The retrieving-effectively-from-memory model (REM; R. M. Shifrrin & M. Steyvers, 1997, 1998) predicts that low-frequency words will be better recognized than high-frequency words because low-frequency words have more distinctive memory representations. A corollary of this assumption predicts that the typical recognition word-frequency effect will be disrupted when similar foils are tested. These predictions were confirmed, but to fit both the recognition and the judgment-of-frequency data, the authors used a "dual-process" extension of the REM model.

Attention↗

Low frequency TENS is less effective than high frequency TENS at reducing inflammation-induced hyperalgesia in morphine-tolerant rats.

Both transcutaneous electrical nerve stimulation (TENS) and morphine are commonly used for relief of pain. Extensive research has been done on the effectiveness of each of these two methods for pain relief when given independently. However, very little literature exists examining the effectiveness of their combined use. Systemically administered morphine activates mu opioid receptors and when administered for prolonged periods results in analgesic tolerance. Low (4 Hz) and high (100 Hz) frequency TENS activate mu- and delta-opioid receptors, respectively, It is thus possible that TENS would be less effective in morphine-tolerant subjects. The current study investigated the effectiveness of high- and low-frequency TENS in the reversal of hyperalgesia in inflamed rats that were morphine-tolerant. Morphine tolerance was induced by subcutaneous implantation of morphine pellets over 10 days. Knee joint inflammation was induced by injection of kaolin and carrageenan into the knee joint cavity. Secondary heat hyperalgesia was tested by measuring the paw withdrawal latency to radiant heat (1) before pellet implantation (either morphine or placebo), (2) after pellet implantation and before inflammation, (3) after inflammation and (4) after TENS. Both high (100 Hz) and low (4 Hz) frequency TENS caused nearly 100% inhibition of secondary hyperalgesia in animals receiving placebo pellets. In contrast, the hyperalgesia in morphine-tolerant animals with knee joint inflammation was unaffected by low frequency TENS but fully reversed by high frequency TENS. These results suggest that patients who are tolerant to morphine may respond better to high frequency TENS than to low frequency TENS.

Animals↗