Unilateral impairment of pupillary response to trigeminal nerve stimulation in cluster headache

The pupillary constriction induced ipsilaterally by transcutaneous electrical nerve stimulation (TENS) of the infratrochlear nerve was measured, using an electronic pupillometer, in 26 episodic cluster headache (CH) and 15 migraine sufferers tested during an attack-free period and in 16 healthy controls. In controls, TENS gave rise to a miosis which was slow in onset and long-lasting in duration, and which was comparable to that mediated by tachykinins in animals. A similar miotic response was bilaterally observed in migraine patients and in CH patients examined during the inactive phase. In CH sufferers during the cluster period, TENS only elicited a normal pupillary constriction in the asymptomatic eye, whereas the resulting response in the symptomatic eye was markedly decreased. Although the exact mechanism underlying the dysfunction remains to be clarified, these results seem to indicate that ocular trigeminal pathways are involved in CH.     

The effect of trigeminal nociceptive stimulation on blink reflexes and pain evoked by stimulation of the supraorbital nerve

The aim of this study was to investigate the effect of painful conditioning stimuli on pain and blink reflexes to supraorbital nerve stimulation. Electromyograph activity was recorded bilaterally from the orbicularis oculi muscles in 13 normal participants in response to low (2.3 mA) and high-intensity (18.6 mA) electrical stimulation of the left supraorbital nerve before, during and after the application of ice to the left or right temple or immersion of the left hand in ice-water for 60 s. The pain evoked by the high-intensity electrical stimulus was greater during painful conditioning stimulation of the ipsilateral temple than during the recovery period afterwards, and was greater than during painful conditioning stimulation of the contralateral temple. These findings imply that spatial summation of nociceptive signals across different divisions of the trigeminal nerve can heighten pain. However, painful conditioning stimulation, particularly to the right temple, strongly suppressed the R2 component of the blink reflex to the low-intensity stimulus, and also suppressed R2 to the high-intensity stimulus. Thus, an inhibitory influence (e.g. diffuse noxious inhibitory controls) appeared to mask ipsilateral segmental facilitation of R2 during ice-induced headache. This finding contrasts with recent electrophysiological evidence of trigeminal sensitization in migraine.     

Effects of two different intensities of transcutaneous electrical nerve stimulation on pain thresholds of contralateral muscles in healthy subjects

[Purpose] This study aimed to investigate the differential effects of high-intensity and low-intensity transcutaneous electrical nerve stimulation on the contralateral side on the pain threshold in healthy subjects. [Subjects and Methods] Twenty-five healthy adults, volunteers received two intensity levels (motor-level, 1.5 times the muscle motor threshold; sensory-level, sensory threshold of the common peroneal nerve), for 30 s on separate days. Pressure pain threshold was recorded on the contralateral tibialis anterior and deltoid muscle before, during, and after stimulation. [Results] Motor-level stimulation significantly increased the pressure pain threshold at both muscle sites, while effects of sensory-level stimulation on pressure pain thresholds were significant only at the deltoid site. The percent change in pressure pain thresholds at both sites was significantly higher during motor-level stimulation. [Conclusion] Motor-level stimulation, applied unilaterally to one leg, produced immediate contralateral diffuse and segmental analgesic effects. This may be of therapeutic benefit in patients for whom transcutaneous electrical nerve stimulation cannot be directly used at the painful site.Key words: Transcutaneous electrical nerve stimulation, Pressure pain threshold, Motor-level stimulation     

Morphine-induced mydriasis and inhibition of pupillary light reflex and fluctuations in the cat

Morphine has species-characteristic effects on pupillary size The effects of morphine on pupillary size, fluctuations and the light reflex were tested with an infrared video pupillometer in the gallamine-paralyzed cat. Compared with saline or base-line responses, i.v. morphine (0.06-1.5 mg/kg) caused a dose-related decrease in the light reflex and fluctuations but increased pupil size. Naloxone (1-100 micrograms/kg i.v.), injected 1 h after morphine, reversed all pupillary effects. Levorphanol (0.5 mg/kg i.v.) had pupillary actions like those of morphine, but dextrophan (0.5 mg/kg i.v.) was inactive. Sympathectomy did not alter the morphine response. It was concluded that morphine disrupts parasympathetic innervation of the iris through interactions with opiate receptors, some of which are in the brain. The morphine-induced changes on the light reflex and fluctuations in the cat are opposite those reported in the rat and rabbit. These results enlarge on the familiar species-dependent effects of opiates on pupillary size.     

Evaluation of autonomic nervous function by pupil dynamics recording]

Pupil is richly innervated by autonomic nerves. Therefore, its size or movement well reflects the autonomic nervous function. By analyzing dynamics of pupil movement for light stimulus followed by infrared video-pupillography, the abnormality of autonomic nervous system can be expressed in a quantitative manner. Clinical applications of pupillography and pharmacological examination to Horner syndrome, Adie syndrome, diabetes mellitus, pupillary involvement of Beh?et disease, pupil of brain death and patients with chemical sensitivity have been described. Segmental spasm of iris in Horner and Aide syndrome, especially, nasal side of iridoplegia was seen in early stage of Aide syndrome from pupillary dynamics to light stimulus. An involvement of sympathetic nerve subserving iris dilator muscle was confirmed from pupillography, drug reaction to topically applied l-epinephrine in the diabetics. An involvement of cholinergic nerve which subserve the iris sphincter muscle was seen in Beh?et disease when there was no manifest eye involvement. Mild mydriasis in brain death patients was seen under denervation of central nervous system. Dysfunction of sympathetic nerve from pupillary light reflex in chemically sensitive patients for cholinated hydrocarbon pesticides.     

Substance P Theory: A Unique Focus on the Painful and Painless Phenomena of Cluster Headache

These studies of cluster headache (CH) focus on two key features of pain transmission: a) sensory nerves when stimulated, as well as the expected afferent transmission, also display an efferent function which affects capillaries, glands, and smooth muscle (of the iris in CH); substance P (SP) and allied transmitters such as Vasoactive Intestinal Peptide (VIP) and Calcitonin Gene-Related Peptide (CGRP) are the main agonists of this dual afferent-efferent function; b) impaired pain transmission (deafferentation-like condition) provokes a rostral spread of neuronal irritability and automatic firing ("quasi epileptic foci") producing a clinical predilection for pain with the generation of "spontaneous" pains along the sensory pathways. The substrates studied in the present experiments are the iris, salivary glands, and nasal mucosa. 1) Iris: the conjunctival instillation of SP induces isocoric miosis both in CH sufferers and in normals, thus excluding gross SP receptoral dysfunction of the iris muscle in CH. Electrical stimulation of extraocular (infratrochlear) endings of the first branch of the trigeminal nerve provokes a miosis, which is significantly less in the symptomatic eye than in the contralateral one. This miosis is ascribed to a retrograde release of SP, induced by electrical stimulation of the trigeminal ophthalmic branch. The relatively poor miosis in the painful eye could correlate with a deficient release of SP from the sensory terminals in the iris. 2) Salivary glands: an increase of substance P-like immunoreactivity is found in the saliva taken from the asymptomatic side, but not from the painful side during a cluster headache attack, thus showing at this level also an asymmetry as previously shown in other head structures. 3) Nasal mucosa: intranasal application of capsaicin, a powerful releaser of SP from sensory terminals, evokes an immediate burning pain in the ipsilateral nasal, ocular, and temporal areas, as well as lacrimation and rhinorrhea. A gradual decrease (tachyphylaxis) of these phenomena is consistently observed after few days of daily nasal administration of capsaicin. When this treatment is applied to CH patients, a rapid decrease in the number and intensity of attacks, and even disappearance of symptoms accompanies the decline of the capsaicin-induced manifestations. Local (nasal) capsaicin, in spite of evoking immediately the same vegetative (rhinorrhea, lacrimation, conjunctival congestion) and in part nociceptive (transient nasal, ocular, temporal burning) phenomena of CH, never has been able to provoke delayed spontaneous-CH like attacks. Such delayed provoked attacks, one of the most pregnant phenomena in CH investigations, are almost constantly evoked by systemic stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)     

Comparison of TENS treatments in hemiplegic shoulder pain

The aim of this paper is to evaluate the effectiveness of high-intensity versus low-intensity transcutaneous electrical nerve stimulation (TENS) and versus placebo for treatment of hemiplegic shoulder pain. Three groups of 20 patients each (A, B, C) were studied. In group A high-intensity TENS was delivered at 3 times the sensory threshold with frequency of 100 Hz; in group B low-intensity TENS was delivered at the sensory threshold with frequency of 100 Hz. Group C received placebo stimulation. The treatment protocol consisted of 12 sessions (4 weeks). Before treatment, at the end of it and one month after, passive range of motion (PROM) for flexion, extension, abduction and external rotation were evaluated. Statistically significant improvements of PROMs were recorded for group A, but not for groups B or C.     

Central post-stroke pain--the effect of high and low frequency TENS

The effect of high (conventional) and low frequency (acupuncture-like) transcutaneous electrical nerve stimulation (Hi-, Lo-TENS) was tested in 15 patients with central post-stroke pain. During the initial 16 day trial of stimulation ipsilateral and contralateral to the pain, 4 patients obtained pain relief. Three of them benefitted from ipsilateral Hi- and Lo-TENS. Two patients also obtained pain relief with contralateral stimulation. Three patients continued to use TENS ipsilaterally with good effect at follow-up 23-30 months after the initial trial. In one-third of the patients, TENS temporarily increased the pain.     

Can electroacupuncture or transcutaneous nerve stimulation influence cognitive and emotional outcome after stroke?

OBJECTIVE: The authors know of no controlled randomized studies on the cognitive effects of acupuncture following stroke. The aim of this study is to assess the effects of acupuncture combined with electroacupuncture and transcutaneous electrical nerve stimulation on emotional and cognitive functioning. METHODS: Five to 10 days after stroke, 54 patients with moderate or severe functional impairment were randomized to 1 of 3 interventions: (i) acupuncture, including electroacupuncture; (ii) sensory stimulation with high-intensity, low-frequency transcutaneous electrical nerve stimulation that induced muscle contractions; and (iii) low-intensity (subliminal) high-frequency transcutaneous electrical nerve stimulation (control group). Twenty treatment sessions were performed over 10 weeks. Outcome measures included cognitive performance and emotional functioning. Measures were obtained prior to any stimulation treatment and at 3 and 12 months. RESULTS: At baseline, groups were comparable with regard to demographic, medical, emotional and functional status. The control group demonstrated lower cognitive performances, but this difference did not remain at 3 or 12 months. There were no treatment effects on emotional status. When pooling treatment groups, there were significant cognitive and emotional improvements. CONCLUSION: Although patients from all 3 groups demonstrated cognitive and emotional improvements, the present study does not suggest any treatment effects on emotional status or cognitive functioning.     

The role of ischaemia in the analgesia which follows Bier's block technique.

The effect of 30-min tourniquet ischaemia (Bier's block) on the antidromic homolateral left median nerve sensory potential (SP) and on the bilateral sympathetic skin response (SSR) was studied in 6 healthy volunteers. The SSR was provoked both acoustically and by electrical stimulation of the median nerve; the latter stimulus was also used to provoke the SP. After 28 min of tourniquet ischaemia, the electrical stimulus failed to provoke the SP and bilateral SSR, indicating blockade of the afferent limb of the reflex. The acoustic SSR was unaffected by ischaemia, and thus the efferent limb of the SSR was not blocked, indicating that ischaemia does not affect the post-ganglionic efferent C fibres. These findings confirm that 30 min of ischaemia blocks A beta afferent fibres but does not block efferent C fibres. Thus the analgesia following Bier's block alone, in some patients with sympathetically maintained pain, most likely results from the ischaemic blockade of sensory A beta fibres, confirmed both acoustically and by electrical stimulation of the median nerve.     

Correlations among autonomic, sensory, and motor neural function tests in untreated non-insulin-dependent diabetic individuals

A well-defined group of untreated non-insulin-dependent (NIDD) subjects were evaluated to determine whether involvement of neural function measurements is generalized and symmetrical and to compare the autonomic, sensory, and motor neural measurements. After age adjustment, the sensory and motor neural function measurements were significantly slower in the diabetic group than in normal subjects (P less than 0.01). Similarly, the autonomic nervous system function measurements were also abnormal in the NIDD group (P less than 0.01). Further analysis revealed that each of the specific measurements--median motor nerve conduction velocity (NCV,P less than 0.005), peroneal motor NCV (P less than 0.005), median sensory NCV (P less than 0.005), dark-adapted pupil size after muscarinic blockade (P less than 0.02), pupillary latency time (P less than 0.02), and RR-variation after beta adrenergic blockade (P less than 0.001)--was significantly less by analysis of covariance after age adjustment in the NIDD group than in normal subjects. Thus, there was evidence of motor and sensory neural impairment in the upper and lower extremities as well as evidence of impairment of the reflex arcs involving the parasympathetic nerves to the heart and eye and the sympathetic nerves to the iris. Further analysis revealed that right and left NCV were correlated (P less than 0.01), as were the median motor and median sensory NCV (P less than 0.01), the median motor and peroneal motor NCV (P less than 0.001), and the peroneal motor and median sensory NCV (P less than 0.001). Thus, there was evidence of symmetrical upper and lower limb, as well as motor and sensory proportional involvement of large nerve fiber NCV in this group of NIDD subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Different organization of cat lateral geniculate neurons in binocular inhibitory interaction.

The principal cells of the geniculate nucleus are generally classified into two types in terms of their anatomical connection with the optic nerve fibers; the contralateral geniculate cell on which the contralateral optic nerve fibers make excitatory synapses and the homolateral geniculate cell on which homolateral optic nerve fibers synapse. In the present experiments, the organization of binocular inhibition in the two different types of geniculate cells was investigated in the cats anesthetized with a chloralose-urethane mixture. In homolateral geniculate cells, an action spike produced by a volley in the ipsilateral optic nerve was often suppressed by a conditioning volley in the contralateral optic nerve (binocular inhibition). In the contralateral geniculate neurons, a conditioning volley in the homolateral optic nerve only occasionally inhibited the generation of an action spike produced by a contralateral optic nerve volley. Intracellular recording from the geniculate cells confirmed the results obtained by extracellular studies. It was concluded that binocular interaction at the lateral geniculate level was seen more commonly in the homolateral geniculate cells than in the contralateral cells.     

Escape of parasympathetic vasodilatation from sympathetic attenuation in oro-facial areas in the cat.

We examined the effects of concurrent repetitive stimulation of the cervical sympathetic trunk (CST) on the parasympathetically mediated reflex blood flow increase in the orofacial area of cats. In urethane plus alpha-chloralose anaesthetized cats, parasympathetic reflex vasodilatation in the ipsilateral lower lip was elicited by electrical stimulation of the central cut end of the lingual nerve (LN). This blood flow increase was attenuated in a frequency-dependent manner when CST was stimulated concurrently at 0.5-10 Hz for 10 minutes. When we applied repeated LN stimulation (using identical parameters, each time) at intervals during a 30-minutes period of 10 Hz CST stimulation, the attenuation of the blood flow increase gradually weakened in a time-dependent manner even though the direct vasoconstrictor effect of CST stimulation showed no such decline.     

Comparison of the effective intensity of transcutaneous electrical nerve stimulation contralateral to a pain site for analgesia

[Purpose] This study aimed to compare the effectiveness of transcutaneous electrical nerve stimulation contralateral to the pain site for analgesia to identify the effective stimulation intensity. [Participants and Methods] Ten healthy adult females were recruited for the study. The same heat stimulation was applied to the left wrist joint of each participant to induce pain, serving as the control. Transcutaneous electrical nerve stimulation was then randomly administered to the right wrist, corresponding to the same dermatome contralateral to the painful site, at the intensities of comfortable stimulation, pain threshold, and maximum pain. The effect of transcutaneous electrical nerve stimulation was assessed using a Visual Analogue Scale and by analysis of heart rate variability. [Results] The Visual Analogue Scale score was significantly lower after stimulation with the maximum pain intensity than that for control, and there were no significant differences among the intensities of comfortable stimulation, pain threshold, and maximum pain. No significant differences were found among the groups in terms of high and low-to-high frequency components. [Conclusion] Transcutaneous electrical nerve stimulation at the maximum pain intensity to the dermatome area contralateral to that of the dorsal pain site of the left wrist was considered effective.     

Iris Adrenergic Impairment in Idiopathic Headache

SYNOPSIS
Adrenergic iris neurons were pharmacologically studied in 30 migraineurs, 11 cluster headaches and 30 controls.
The pupillary diameter was measured by photographic technique. When compared with controls, migraineurs showed minor fenfluramine mydriasis and greater, more prolonged guanethidine miosis. No significant differences between the affected and unaffected side were observed by testing with guanethidine in unilateral migraineurs.
A poor concentration and synthesis of noradrenaline in the pupil terminals is hypothesized. Moreover, increased mydriasis observed with phenylephrine suggests alpha adrenoceptor supersensitivity from a defect of neuronal transmitter.
In cluster headaches, only a minor tyramine mydriasis was found in the affected pupil. This suggests low availability of neuronal transmitter or a defect of the synaptic tyramine re-uptake in the affected cluster pupil. A disorder of the iris adrenergic neurons could mirror an impairment in the central aminergic systems of idiopathic headaches.     

Blink reflex R2 amplitudes in cervicogenic headache, chronic tension-type headache and migraine

Blink reflex R2 amplitude was investigated in seven patients with cervicogenic headache (CEH), 12 patients with chronic tension-type headache, 23 patients with migraine (10 with aura) and 17 headache-free controls. Standard electrical stimulation of the supraorbital nerve was applied and the response was recorded from the ipsilateral and the contralateral orbicularis oculi muscles. Low R2 amplitude was found in CEH patients compared with control subjects. Headache is unilateral in CEH and the ipsilateral and contralateral responses after stimulation on the painful side were most depressed. R2 amplitude was not significantly affected in migraine and tension headache patients. The results suggest that lower brainstem excitability is reduced in CEH. A state of hypoactivity may be present in caudal trigeminal nucleus neurons on the symptomatic side.     

Cholinergic manifestations of the acute autonomic reaction to hypoglycaemia in man

1. The effects of insulin-induced hypoglycaemia on pupil size, parotid salivary secretion and sweating were studied in seven normal volunteers. 2. Hypoglycaemia was associated with an acute stimulation of parotid salivary secretion and of sweating, synchronous in onset with the rise in heart rate. There was no clear evidence of concurrent pupillary constriction.     

The Enhanced Ciliospinal Reflex in Asymptomatic Patients With Cluster Headache is Due to Preganglionic Sympathetic Mechanisms

An amplified ciliospinal reflex response has been documented in patients with cluster headache, lacking a Horner like syndrome. The mechanism is unknown, Tentatively, it may be due to an increased release of monoamines from post-ganglionic sympathetic nerve endings or an increased density of postsynaptic adrenergic receptors in the dilatator muscle of the iris.
The instillation of a 1% phenylephrine solution into the conjunctival sac induces mydriasis by stimulating postsynaptic adrenergic receptors in the dilatator muscle of the iris, while the instillation of a 2% tyramine solution causes mydriasis by releasing noradrenaline from the presynaptic sympathetic nerve terminals in the iris.
According to these premises, a positive correlation shouId be expected between the ciliospinal reflex response and the pupillary response to tyramine, if the enhanced ciliospinal so-flex response was due to an increased presynaptic release of monoamines. No such correlation was found. Nor was there any positive correlation between the ciliospinal reflex response and the pupillary response to phenylephrine, contradicting an increased density of postsynaptic monoaminergic receptors in the dilatator muscle of the iris as the explanation. However, there was a significant positive correlation between the pupillary responses to phenylephrine and tyramine, ruling out any functionally caused "denervation" hypersensitivity in the dilatator muscle of the iris.
It is concluded that the amplified ciliospinal reflex response in cluster headache patients (lacking a Horner-like syndrome) reflects compensatory pathophysiological mechanisms proximal to the third-order sympathetic neuron.     

Anisocoria and mydriasis after scalp nerve block: a case report

Strategies for the assessment of abnormal neurological findings during general anesthesia are limited. However, pupil abnormalities may represent serious neurological complications. We herein present a case of new-onset anisocoria and mydriasis that developed after scalp nerve block. The patient’s signs were possibly related to increased intracranial pressure with resulting brain shift that ultimately affected the oculomotor nerves. A 45-year-old man was scheduled for left cerebellar tumor resection and ventricular drainage surgery; however, anisocoria and left pupillary mydriasis were observed after induction of general anesthesia and performance of scalp nerve block. After reducing the intracranial pressure, the right pupil showed constriction (1 mm) but the left pupil was dilated (5 mm). The pupils were of similar size postoperatively. Although pupillary dilation during general anesthesia has been previously described, this is the first case in which the mydriasis was considered to have been caused by brain shift due to increased intracranial pressure after scalp nerve block. Thus, we propose this phenomenon as a new possible cause of pupillary changes. Actively monitoring this presentation intraoperatively could enable early detection of and intervention for complications, therefore improving the prognosis.     

Transcutaneous electrical nerve stimulation characteristics for altering pain perception

The purpose of this study was to determine the effect of conventional low-intensity transcutaneous electrical nerve stimulation (TENS) waveform and frequency characteristics on experimentally induced acute pain. Each of 28 male subjects received six forms of TENS and one control treatment during a single testing session. Treatments used one of two waveforms (monophasic or biphasic) and one of three frequencies (30, 60, or 85 Hz) administered to the forearm. Treatment effects were ascertained from alterations in pain-threshold and pain-tolerance responses induced by noxious electrical stimulation of the ipsilateral fifth digit. The TENS waveform and frequency had a negligible effect on pain threshold. The results indicated that waveform did not influence pain tolerance significantly. Pain tolerance, however, increased significantly at the frequency of 60 Hz but decreased significantly at both 30 and 85 Hz (p less than .05). We concluded that TENS frequency is an important factor in altering the subjects' perception of experimentally induced pain.