Contralateral Effects Research Articles

Effect of unilateral injection of MK-801 into the area of A10 cells on feeding evoked by stimulation of homologous area in the contralateral hemisphere

It was found previously that unilateral electrolytic and 6-OHDA lesions of the ventral tegmental area (VTA) and unilateral intra- VTA injection of bicuculline resulted in facilitation of behavioral responses evoked by electrical stimulation of the symmetrical VTA area in the contralateral hemisphere. We postulated that "the contralateral facilitation effect", which may reflect the yet unexplored mechanism of immediate compensation after acute unilateral brain injury, is attributable to the A10 DA neurons and their regulatory inputs. The present study was aimed at examining the possible involvement of NMDA-mediated glutamatergic transmission in VTA in the "contralateral facilitation effect". The behavioral model of the VTA stimulation-induced feeding in rats was used. Latency to eat was measured as a function of stimulation frequency before and after unilateral intra-VTA injection of non-competitive NMDA receptors antagonist, MK-801, (doses 0.0, 1.25 and 2.5 micrograms), MK-801 caused a dose-dependent augmentation of feeding evoked by stimulation of the contralateral VTA, which manifested as a decrease in the reaction frequency threshold and a leftward shift of the latency/frequency curve. Dose 2.5 micrograms replicated the facilitatory effect of electrolytic and 6-OHDA lesions. The results are interpreted in terms of MK-801-evoked depression of excitatory glutamatergic tone over A10 DA cells and compensatory increase in DA release in the contralateral hemisphere.

Contralateral effect of topical β-adrenergic antagonists in initial one-eyed trials in the Ocular Hypertension Treatment Study

PURPOSE: To evaluate the magnitude of the contralateral effect of topically administered β-blockers on intraocular pressure. METHODS: The Ocular Hypertension Treatment Study enrolled 1,636 subjects. Of these, 817 subjects were randomized to receive topical ocular hypotensive medication and 819 subjects were randomized to close observation (i.e., no topical medication). We compared the intraocular pressure of the contralateral eye of subjects at the baseline visit and after an initial one-eyed therapeutic trial of topical β-blockers. We examined differences between baseline and follow-up intraocular pressure in untreated eyes of subjects randomized to close observation. RESULTS: The mean reduction in intraocular pressure in the β-blocker–treated eyes was −5.9 ± 3.4 mm Hg (−22% ± 12%; Student t test, P < .0001). In the contralateral eyes, mean intraocular pressure reduction was −1.5 ± 3.0 mm Hg (−5.8% ± 12%; P < .0001). Of the contralateral eyes, 35% showed a reduction of 3 mm Hg or more, and 10% showed a reduction of 6 mm Hg or more. The contralateral effect of the relatively selective β-blocker betaxolol did not differ from that of any of the nonselective β-blockers. Factors associated with the magnitude of the contralateral effect were the degree of intraocular pressure reduction in the treated eye and baseline intraocular pressure of the contralateral eye. In the close observation group, no significant reduction in intraocular pressure was noted between the baseline and follow-up visit. CONCLUSIONS: The contralateral effect is important in clinical practice and in clinical trials when the hypotensive effect of a topical β-blocker is evaluated by means of a one-eyed therapeutic trial.

Competition in Early Exogenous Orienting between 7 and 21 Weeks

Exogenous (stimulus-driven) orienting between 7 and 21 weeks of age was examined in 2 experiments using a display with multiple potential targets of attention. On each trial a small moving probe was used to draw attention to one side of the display or the other. This moving probe appeared simultaneously with 27 static bars. In the first experiment, sensitivity to the moving target was affected significantly by the spatial distribution of these red and green static bars for 14-week-olds but not for 8-week-olds. Sensitivity to the moving target was lower for 14-week-olds when most of the red bars appeared contralaterally to the moving target. This effect replicated a similar effect observed in J. L. Dannemiller (1998). The lack of a contralateral competition effect in Experiment 1 for the 8-week-olds may have occurred because I used a stronger motion stimulus for the younger infants in an attempt to hold the overall performance constant at the 2 ages. A second experiment using a weaker motion stimulus showed that this contralateral competition effect was observable over the entire age range from 7 to 21 weeks of age. Thus as early as 7 weeks of age, sensitivity for a small moving stimulus can be significantly influenced by the simultaneous presence of competing targets of attention in the visual field. Large increases in overall sensitivity were also found across the age range from 7 to 21 weeks. Results are discussed in terms of the development of putative competition mechanisms involved in exogenous orienting.

Tones disappear faster in the right ear than in the left.

In order to gain further information on the characteristics and physiological correlates of tone decay in humans, the tone decay test was administered to 58 normal-hearing subjects, successively in the left and right ears and in absence and presence of a contralateral noise. The results revealed that tone decay was greater in the right than in the left ear and was increased by contralateral noise. The contralateral effect of this noise on cochlear biomechanisms was then estimated by measuring contralaterally induced variations in the amplitude of click-evoked otoacoustic emissions in the same subjects. In the right ear, the increase in tone decay and the decrease in otoacoustic emission amplitude--both induced by contralateral noise--were positively correlated (r = .315, p = .016). Furthermore, the contralateral changes in otoacoustic emission amplitude were found to be on average larger in the right than in the left ear, this asymmetry being correlated with that observed for the tone decay. These findings are discussed in relation to previous results on simple and induced loudness adaptation in the vicinity of threshold, on contralateral attenuation of otoacoustic emissions and on the influence of the auditory efferents on cochlear biomechanisms.

Inter-ocular characteristics of the pre-contact lens tear film

To establish whether the status of the pre-contact lens tear film as indicated by standard, clinical observational techniques is affected by moderate stimulation of the contralateral eye. Four indicators of tear film behavior, lipid layer appearance, amount of debris, inferior meniscus height and non-invasive tear break up time (NIBUT) were monitored in ten subjects before and during 30 minutes of monocular pHEMA contact lens wear. Concurrently, the contralateral eye was either subjected to moderate irritation by means of a silicone elastomer contact lens, or remained unstimulated. Data were compared, between the stimulated and unstimulated states to identify evidence of contralateral treatment effects. After 30 minutes, maximum contralateral differences between the unstimulated and stimulated conditions were 1 grade for both lipid layer appearance and debris, 0.1 mm for meniscus height and 4 secs for NIBUT. The magnitudes of contralateral effects induced by moderate, monocular irritation were comparable with the within-subject variabilities associated with these indicators of tear film behavior.

A Lesion Analysis of Visual Orienting Performance in Children With Cerebral Vascular Injury

Anterior brain insults during development have been shown to result in visual orienting deficits; however, the type of orienting deficit has varied across studies. Performance on an orienting task was examined in relation to the location and volume of injury on magnetic resonance exams in 15 children with cerebral infarction and 32 control children. Contralateral lesions including the parietal lobe were associated with larger validity effects, suggesting difficulties disengaging attention. A similar trend was found for the middle-frontal gyrus. Basal ganglia injury contralateral to a given hemifield was associated with less facilitation of attention. Lesion volume in each hemisphere did not show a significant relation with contralateral validity effects. The data suggest that variability in the type of visual orienting deficits shown in prior studies of children with anterior brain insults may be related in part to the specific location of lesions within the frontal lobe.

Contralateral treatment with xylocaine reduces nociceptive behaviour in mononeuropathic rats.

The aim of the present study was to establish whether contralateral treatment with local anaesthetics reduces nociceptive behaviour in mononeuropathic rats. Contralateral treatment with xylocaine on day 6 and 11 following sciatic nerve ligation increased withdrawal latencies to thermal but not to mechanical stimulation for 3-4 days. Rats who received contralateral treatment with xylocaine on day 6 and 11 showed a reduced autotomy score during the following 6 weeks. To compare ipsilateral and contralateral effects another set of experiments was performed. Rats treated contralaterally on day 11 had a significantly lower autotomy score at week 4 and 6. Our results demonstrate that contralateral treatment with xylocaine reduces nociceptive behaviour in mononeuropathic rats for days or weeks.

Paradoxical Effects of Contralateral White Noise on Evoked Otoacoustic Emissions in Ears with Acoustic Neuroma

A contralateral suppression effect on evoked otoacoustic emissions (EOAEs) is usually present in normally hearing subjects and in patients with sensorineural hearing loss, while it is absent or reduced in ears to which the vestibular nerve has been cut and in ears with acoustic neuroma (AN). To date, a paradoxical effect, that is an increase in EOAE amplitude during contralateral stimulation, has been described in one ear with sensorineural hearing loss of unknown aetiology and in three ears with AN (two in the present paper). Evidence has been provided that the contralateral suppression effect on EOAEs is accomplished largely, if not entirely, via the medial olivocochlear bundle (OCB). According to clinical data the absence or the reduced amount of contralateral suppression effect on EAOEs may be attributed to a totally, or partially, damaged or malfunctioning medial OCB. The way in which a contralateral noise may increase EOAE amplitude is more difficult to explain. One attractive hypothesis is that this paradoxical effect is a result of some pathological adaptive process in the medial OCB.

Inter-ocular characteristics of the pre-contact lens tear film

Purpose. To establish whether the status of the pre-contact lens tear film as indicated by standard, clinical observational techniques is affected by moderate stimulation of the contralateral eye. Methods. Four indicators of tear film behavior, lipid layer appearance, amount of debris, inferior meniscus height and non-invasive tear break up time (NIBUT) were monitored in ten subjects before and during 30 minutes of monocular pHEMA contact lens wear. Concurrently, the contralateral eye was either subjected to moderate irritation by means of a silicone elastomer contact lens, or remained unstimulated. Data were compared, between the stimulated and unstimulated states to identify evidence of contralateral treatment effects. Results. After 30 minutes, maximum contralateral differences between the unstimulated and stimulated conditions were 1 grade for both lipid layer appearance and debris, 0.1 mm for meniscus height and 4 secs for NIBUT. Conclusions. The magnitudes of contralateral effects induced by moderate, monocular irritation were comparable with the within-subject variabilities associated with these indicators of tear film behavior.

Facilitatory effect of unilateral lesion of the ventral tegmental area on locomotor response to stimulation of the contralateral ventral tegmental area: involvement of GABAergic transmission

It was found previously that in the rat, unilateral electrolytic lesion of the ventral tegmental area (VTA) facilitated feeding induced by electrical stimulation of the homologous VTA tissue in the contralateral hemisphere. In the present work, VTA stimulation-induced locomotor response was tested in male Wistar rats using a latency to move/stimulation frequency curve shift paradigm in order to check for functional generality of the “contralateral facilitation effect” and also with the aim of elaborating an easy and reliable behavioral model to study this phenomenon. In a further step, the hypothesis was tested that enhancement of function of the intact VTA results from elimination of tonic GABAergic influence derived normally from the lesioned VTA. GABA A (bicuculline, doses 0, 0.5 and 5.0 ng) and GABA B (phaclofen, doses 0, 500 and 1000 ng) receptors antagonists, and for comparison, a GABA A receptor agonist (muscimol, doses 0, 12.5, 25.0 and 50.0 ng), were injected unilaterally to VTA and their effect on locomotor response elicited by electrical stimulation of the contralateral VTA was tested in a latency/frequency paradigm. It was found that similar to feeding, locomotor response evoked by unilateral electrical stimulation of the VTA was facilitated after contralateral VTA lesion which manifested as a decrease of the locomotion threshold and a leftward shift of the function relating latency to move to stimulation frequency. The effect was immediate, long-lasting and specific to the VTA destruction; lesions outside the VTA area caused gradual impairment of the locomotor response to stimulation. The facilitatory effect of the electrolytic lesion could be replicated by bicuculline, which significantly facilitated stimulation-induced behavior. Phaclofen exerted slight facilitating influence only at a low dose. No effect of muscimol on the locomotion threshold was found. We conclude that “the contralateral facilitation effect” at the level of VTA reflects the interhemispheric regulation of activity of the dopaminergic (DA) cells in which GABA A-mediated interhemispheric communication plays a significant role.

Tactile stimulation of the hand causes bilateral cortical activation: a functional magnetic resonance study in humans

The purpose of the present study was to assess the somatotopy of the cortical sensory representation of the fingers using a natural tactile stimulation of the glabrous skin. Multislice echoplanar imaging techniques were utilized to investigate blood oxygen level dependent (BOLD) signal changes as a measure of cortical activation. Repetitive sensory stimulation of the glabrous skin of digit II–III and digit IV–V resulted in a multifocal signal increase in a restricted area near the central sulcus in the contralateral hemisphere with a considerable overlap between the activated areas of digit II–III and digit IV–V. In addition, in all subjects tactile stimulation resulted in ipsilateral signal increase near the central sulcus, which was 15–22% of the contralateral effect. Stimulation of digit II–III caused significantly ( P<0.05) more activated voxels than digit IV–V in the contralateral hemisphere for both hands and for the left hand in the ipsilateral hemisphere. These findings suggest an ipsilateral activation of the primary somatosensory cortex during a natural tactile stimulation of the digits in humans.

Prediction of postoperative seizure control by hippocampal event-related potentials.

In spite of unequivocal results of the presurgical evaluation, between 10 and 30% of patients with medial temporal lobe epilepsy (MTLE) do not become seizure free by temporal lobe surgery. Because event-related potentials (ERPs) recorded within the hippocampal formation have been shown to be sensitive to the epileptogenic process, we examined whether ERPs can help to improve the prediction of postoperative seizure control. We recorded ERPs to words from bilateral intrahippocaampal electrodes by using a visual word-recognition paradigm in 70 patients with unilateral hippocampal pathology and related these measurements to seizure outcome after temporal lobe surgery. Words elicited N400 potentials, which were reduced in amplitude on repetition on the side contralateral to hippocampal sclerosis. This contralateral repetition effect, however, was significantly diminished in the group of patients who experienced seizure recurrence after the operation. Contralateral repetition effects thus permitted correct prediction of postoperative seizure control in 94% of all patients. Recording ERPs to words within the medial temporal lobes can improve the prediction of postoperative seizure control. Reduced repetition effects contralateral to the side of hippocampal sclerosis may indicate bilateral epileptogenicity.

Persistent neuronal density changes related to the establishment of a motor memory

Rats were trained in a lateralized reaching motor task during either an `early' (22–31 days old) or a `late' (62–71 days old) postnatal period. The `late' group showed significant neuronal density reduction in cortical layers II–III of the contralateral motor forelimb representation. The `early' group evidenced a similar localized contralateral effect that persisted after a subsequent period without training. Furthermore, in this group, a bilateral overall decrease in neuronal density was found throughout the motor cortex. This bilateral experience and age-dependent effect is conceivably related to a critical period of motor cortical development. The localized reduction of neuronal density strongly indicates a morphological expression of the motor engram. Our present study supports the concept that the acquisition and retention of motor learning involves the persistence of structural changes in the brain.

Motor imagery theory of a contralateral handedness effect in recognition memory: Toward a chiral psychology of cognition.

The assumption that cognitive processes are independent of handedness was questioned. Five experiments with left-handed and right-handed participants centered on investigating recognition memory for the orientation of heads. Their results provided consistent evidence of a general contralateral handedness effect: Left-facing heads are more likely to be remembered correctly by right-handed participants, whereas right-facing heads are more likely to be remembered correctly by left-handed participants. Motor imagery and hemispheric differences explanations were compared. The results supported the hypothesis that the effect is a consequence of differences between handedness groups in terms of specific patterns of underlying motor activation rather than in terms of more general differences in function between cerebral hemispheres. The possibility of a chiral psychology of cognition that takes note of a person's handedness is considered.

Vasopressin in the locus coeruleus and dorsal pontine tegmentum affects posture and vestibulospinal reflexes

Vasopressin (VP) acts on both the locus coeruleus (LC) neurons and the neighbouring dorsal pontine reticular formation (PRF) neurons by exciting them. Experiments performed in precollicular decerebrate cats have shown that microinjection of 0.25 x 10(-11) micrograms VP into the LC complex of one side increased the extensor rigidity of the ipsilateral limbs, while rigidity of the contralateral limbs remained unmodified or slightly decreased. The amplitude of modulation and thus the response gain of both the ipsilateral and the contralateral forelimb extensor triceps brachii to sinusoidal roll tilt of the animal (at 0.15 Hz, +/- 10 degrees), leading to stimulation of labyrinth receptors, decreased significantly, while there was only a slight decrease in phase lead of the responses. These effects occurred 5-10 min after the injection, were fully developed within 30 min and disappeared in about 2 h. VP activation of presumed noradrenergic LC neurons had a facilitatory influence on ipsilateral limb extensor motoneurons, either directly through the coeruleospinal (CS) pathway, or indirectly by inhibiting the dorsal PRF and the related medullary inhibitory reticulospinal (RS) neurons. Moreover, because the facilitatory CS neurons fire out-of-phase with respect to the excitatory VS neurons, we postulated that the higher the firing rate of the CS neurons in the animal at rest, the greater the disfacilitation affecting the limb extensor motoneurons during side-down animal tilt. These motoneurons would then respond less efficiently to the excitatory VS volleys elicited for the same direction of animal orientation, leading to a reduced gain of the EMG responses of the forelimb extensors to labyrinth stimulation. In contrast to these findings, unilateral injections of the same dose of VP immediately ventral to the LC, i.e., in the peri-LC alpha and the surrounding dorsal PRF, where presumed cholinergic neurons are located, decreased extensor rigidity in the ipsilateral limbs while that of the contralateral limbs either decreased or increased. The same injection also produced either a moderate or a marked increase in gain of the multiunit EMG response of the ipsilateral triceps brachii to animal tilt. In the first instance the response gain of the contralateral triceps brachii to animal tilt increased slightly, while the corresponding response pattern remained unmodified, as shown for the ipsilateral responses (increased EMG activity during ipsilateral tilt and decreased activity during contralateral tilt). In the second instance, however, the response gain of the contralateral triceps brachii showed only slight changes, while the pattern of response was reversed. These effects occurred 5-20 min after the injection, developed fully within 20-60 min and disappeared in 2-3 h. We postulated that VP increased the discharge of the dorsal PRF neurons and the related medullary inhibitory RS neurons of the injected side, leading to reduced postural activity of the ipsilateral limbs. However, because these inhibitory RS neurons fire out-of-phase with respect to the excitatory VS neurons, it appeared that the higher the firing rate of the RS neurons in the animal at rest, the greater the disinhibition affecting the limb extensor motoneurons during ipsilateral tilt. These motoneurons would then respond more efficiently to the same excitatory VS volleys elicited by given parameters of stimulation, leading to an increased gain of the EMG responses. The contralateral effects could be attributed to crossed excitation by dorsal PRF neurons of one side, either of medullary inhibitory RS neurons or of excitatory CS neurons of the opposite side, respectively. We conclude that VP controls posture and gain of the VS reflex by acting on LC neurons as well as on dorsal PRF and the related medullary inhibitory RS neurons.

Motor imagery theory of a contralateral handedness effect in recognition memory: Toward a chiral psychology of cognition.

Motor imagery theory of a contralateral handedness effect in recognition memory: Toward a chiral psychology of cognition.

Contralateral suppression of transiently evoked otoacoustic emissions by harmonic complex tones in humans.

Variations in the amplitude of transiently evoked otoacoustic emissions (TEOAEs) produced by a contralateral complex tone were measured in 26 normal-hearing human subjects. TEOAEs were evoked using a 1-kHz tone pip at 60 dB SPL. The contralateral complex consisted of harmonic components with frequencies between 400 and 2000 Hz; it was presented at levels ranging from 40 to 50 dB SL and its fundamental frequency (F0) was varied. In experiment 1, the dependence of TEOAE amplitude variations on the F0 of the contralateral complex was measured by varying the F0 from 50 to 400 Hz in octave steps. The results revealed a nonmonotonic dependence of TEOAE amplitude variations on contralateral F0, with significantly larger TEOAE suppression for F0's of 100 and 200 Hz than for F0's of 50 and 400 Hz. Experiment 2, in which the harmonics were summed in alternating sine-cosine phase instead of constant sine phase, showed a shift of the function relating TEOAE attenuation to F0 towards lower F0's, indicating that the waveform repetition rate, rather than harmonic spacing, was the actual factor of the dependence of contralateral TEOAE attenuation on F0. Furthermore, significantly smaller suppression was observed with the alternating-phase complexes than with the sine-phase complexes, suggesting an influence of the waveform crest factor. Experiment 3 showed no difference between the contralateral TEOAE attenuation effects produced by positive and negative Schroeder-phase complexes. Overall, these results bring further arguments for the notion that contralaterally induced medial olivocochlear bundle (MOCB) activity, as measured through the contralateral suppression of TEOAEs in humans, is sensitive to the rate of temporal envelope fluctuations of the contralateral stimulus, with preferential rates around 100-200 Hz.

Topical verapamil and episcleral venous pressure

ObjectiveTo investigate the effect of a single-dose and 2-week administration of topical 0.25% verapamil on episcleral venous pressure (EVP) and intraocular pressure (IOP). DesignA prospective, randomized, double-masked, crossover, and placebo-controlled study. ParticipantsOne eye of each of 20 normal subjects received topical verapamil or placebo. InterventionThe EVP was measured using a pressure chamber episcleral venomanometer. The IOP, EVP, heart rate (HR), and blood pressure (BP) were measured at baseline, 1.5 hours after a single drop, and after 2-week, three-times-a-day topical administration of 0.25% verapamil or placebo to one eye. After a 4-week washout period, the treatment to the study eye was reversed, and measurements of EVP, IOP, HR, and BP were repeated. Main outcome measuresThe EVP, IOP, HR, and BP were measured. ResultsNinety minutes after a single drop, the EVP in the verapamil-treated eyes was reduced by 4.8% (P = < 0.001) and in the untreated fellow eyes by 2.4% (P = 0.032). After 2-week topical administration, the EVP was reduced by 9.5% (P = < 0.0001) in the verapamil-treated eyes and by 4.8% (P = 0.001) in the fellow eyes. The EVP was unchanged in the treated and fellow eyes after a single drop or after a 2-week treatment with placebo. Ninety minutes after topical administration of 0.25% verapamil, the IOP decreased by 7.7% (P = < 0.0001) in the treated eyes and decreased by 3.6% (P = 0.03) in the fellow eyes. After a 2-week administration of topical verapamil, the IOP decreased by 12% (P = 0.0001) in the treated eyes and by 7.2% (P = 0.0289) in the fellow eyes. The changes of IOP in the placebo-treated and fellow eyes were not statistically significant after a single-dose and 2-week administration. After topical administration of verapamil, a contralateral effect on IOP and EVP was observed in the fellow, untreated eye. No systemic effect on HR or BP was detected after a single-dose administration of topical verapamil. There were, however, significant reductions in HR and BP after a 2-week treatment with topical 0.25% verapamil. ConclusionThese results indicate that a single drop and a 2-week administration of topical 0.25% verapamil decrease IOP and EVP significantly, with more pronounced reduction after a 2-week treatment than after a single-dose treatment.

Evidence for efferent effects on early components of the human auditory brain-stem evoked potentials

Objectives and methods: Auditory brain-stem evoked potentials (ABEPs) were recorded from 10 normal hearing subjects in response to rarefaction clicks, presented at a rate of 11/s. Stimuli were binaurally symmetrical and isochronic at 75 dB peSPL or with interaural time disparities (ITDs) of ±0.4 ms, or intensity disparities (IIDs) of ±10 dB. Potentials were recorded from vertex-neck, as well as from 3 orthonormally positioned differential derivations. The amplified potentials were averaged over 8000 repetitions using a dwell time of 20 μs/address/channel. The effects of contralateral stimulation on neural responses of the peripheral auditory system were obtained by subtracting the binaural response from the algebraic sum of responses to left and right monaural stimuli. From the 3 orthonormal derivations, 3-channel Lissajous' trajectories (3-CLTs) to the various stimulus conditions and difference waveforms were derived. Results: The results corroborated earlier studies on binaural interaction components (BICs), which include 3 major components corresponding in latency to the vertex-mastoid peaks IV–VI of ABEP. In addition, the binaural difference waveforms included 3 earlier, low-amplitude components. Latency correspondence and comparison of difference waveform and ABEP 3-CLTs indicated that the first and third early difference waveform components corresponded to the negative peaks following I and III, respectively, of the vertex-neck ABEP to binaural clicks. Conclusions: These results indicate that early ABEP peaks, generated peripheral to binaural convergence, may be affected by contralateral stimulation. These contralateral effects were in a pattern compatible with suppression. most probably by efferents of the olivo-cochlear bundle.

Photochemically-induced ischemia of the rat sciatic nerve produces a dose-dependent and highly reproducible mechanical, heat and cold allodynia, and signs of spontaneous pain

Sensory abnormalities and changes in spontaneous behavior were examined after a photochemically induced ischemic lesion of the rat sciatic nerve. Male adult rats were anesthetized and the sciatic nerve was exposed. After the intravenous injection of a photosensitizing dye, erythrosin B, the exposed nerve was irradiated just proximal to the nerve trifurcation with light from an argon laser. Three different irradiation times were used, 30 s, 1 and 2 min. In sham-operated rats, the exposed sciatic nerve was irradiated for 2 min without prior injection of the erythrosin B. Rats were tested for the presence of mechanical, cold and heat allodynia or hyperalgesia. All the animals in the 1- and 2-min irradiation groups developed mechanical, cold and heat allodynia after nerve irradiation. A significant dose-dependent effect of laser exposure time was observed for all modalities tested (2 min>1 min>30 s=sham). The maximum effects were observed at 3 and 7 days postirradiation and remained present for up to 10 weeks. No significant contralateral effects were observed in any of the groups. In three separate groups of rats (1, 2 and 4 min of laser exposure), the presence of possible signs of spontaneous pain (paw shaking, paw elevation and freezing behavior) was tested. A significant and exposure time-dependent increase in spontaneous paw elevation and paw shaking was observed which was maximal at week 1, but resolved at 4 weeks (4 min>2 min>1 min>sham). In addition, animals in all ischemic groups, but not in the sham group, showed a significant increase in freezing behavior up to 4 weeks after nerve irradiation. Light microscopic evaluation of nerves removed 7 days post-irradiation, i.e. when maximal allodynia was observed, showed clear evidence of demyelination of large myelinated fibers. These data indicate that photochemically-induced peripheral nerve ischemia is associated with abnormal pain-related behaviors, including mechanical, thermal and cold allodynia and signs of spontaneous pain. The incidence and severity of the behavioral changes are clearly dependent on the exposure time and are probably due to, at least in part, a demyelinaton. These results partly confirm previous data using a similar technique and suggest that this may represent a new animal model for peripheral neuropathy of ischemic origin. The advantages of the present model are its good reproducibility and the fact that the nerve injury can be easily quantified and graded.