Pupillary Reflex Dilation Research Articles

Parasympathetic Mediated Pupillary Dilation Elicited by Lingual Nerve Stimulation in Cats

To determine the autonomic efferent nerve pathways for the reflex pupillary dilation elicited by somatic stimulation in cats. Cats anesthetized with a mixture of alpha-chloralose (50 mg/kg) and urethane (100 mg/kg) were intubated and paralyzed by intravenous injection of pancuronium bromide. The central cut end of the lingual nerve (LN) was stimulated electrically to simulate somatic stimulation, and 1 microL of lidocaine (2%) was microinjected into the Vsp or the EW nucleus to determine its effect on the pupillary dilation induced by LN stimulation. The effect of electrically stimulating the Vsp or sectioning the superior cervical sympathetic nerve (CSN) on the pupillary response was also examined. Stimulation of the LN or the trigeminal spinal nucleus (Vsp) evoked pupillary dilation in a frequency- and intensity-dependent manner. These responses were not affected by sectioning the ipsilateral or both CSNs. The pupillary responses were markedly suppressed by microinjecting lidocaine into the ipsilateral Vsp or the Edinger-Westphal (EW) nucleus, but not by injection into the contralateral Vsp. These results indicate that the Vsp and EW nucleus act as bulbar relay centers for pupillary dilation elicited by LN stimulation and suggest that the efferent arc of the response is a parasympathetic pathway. The contralateral pupillary dilation appears to be mediated, at least in part, by fibers projecting from the Vsp to the contralateral EW nucleus.

Latency of pupillary reflex dilation during general anesthesia.

Areas of insensibility produced by neuraxial anesthesia or peripheral nerve blocks can be detected during general anesthesia by failure of noxious stimulation to trigger pupillary reflex dilation. We examined the latency of pupillary reflex dilation and the effect of fentanyl on the latency of reflex dilation during anesthesia in nine volunteers. We hypothesized that the reflex was generated by slowly conducting C nociceptive fibers and would be significantly delayed if a distal dermatome (L(4)) was stimulated compared with a proximal dermatome (C(5)). We also hypothesized that fentanyl would prolong the latency and alter the shape of the reflex. After induction of general anesthesia, pupillary reflex dilation was measured with an infrared pupillometer every 5 min after stimulations of the L(4) and C(5) dermatomes. Fentanyl (3 microg/kg) was then given intravenously. Pupillary reflex dilation latencies were calculated by examining each individual measurement. After 3 h, naloxone (400 microg) was given intravenously; anesthesia was then discontinued. Pupillary reflex dilation had a long latency and consisted of distinct early and late phases. No differences were found between latencies of reflex dilation after simulation of L(4) and C(5) dermatomes either before or after fentanyl administration. Fentanyl at high concentrations essentially eliminated pupillary reflex dilation; but over the 180-min observation period, first early and then late dilation returned. Fentanyl produced a small increase in the latency of the initial early dilation. We conclude that pupillary reflex dilation during anesthesia is not initiated by slowly conducting C fibers and that fentanyl depresses the reflex in a stereotypical manner.

Mechanism of pupillary reflex dilation in awake volunteers and in organ donors.

The mechanism of reflex pupillary dilation was investigated in eight patients who were declared brain dead after rupture of intracranial vascular malformations and in eight awake volunteers. The authors hypothesized that the reflex was primarily a spinal sympathetic reflex that would be blocked by topical application of the alpha1-adrenergic blocking agent dapiprazole and that it would be present in organ donors with intact spinal reflexes and no history of hypoxia. In volunteers, pupil size was measured with an infrared pupillometer while brief painful electric stimuli were delivered to the finger. Pain was assessed with a visual analog scale and adjusted with each volunteer to equal 3 on a visual analog scale of 0-10. Subjects were studied before and after topical application of the alpha1-adrenergic antagonist dapiprazole. In organ donors, the authors measured pupil size after high-intensity tetanic electric stimulation and in dapiprazole-blocked and -unblocked pupils after surgically induced nociception. In volunteers, the pupil dilated 0.43 +/- 0.23 mm after nociceptive stimuli. Dapiprazole eyedrops blocked this dilation, confirming that the reflex in awake humans is primarily a sympathetic reflex. Baseline diameters were 5.7 +/- 0.5 mm before dapiprazole and 4.1 +/- 0.9 mm after dapiprazole. In organ donors, a tetanic electric current failed to dilate the pupil, whereas the skin incision dilated the pupil 0.4 +/- 0.4 mm, but this dilation was not blocked by dapiprazole. The authors conclude that pupillary reflex dilation, as it is clinically performed in awake subjects by stimulating somatic nociceptors, is a sympathetic reflex. Because it is not present in organ donors, the neural pathway must require a supraspinal component for completion.

Effect site concentrations of remifentanil and pupil response to noxious stimulation

Opioid drugs block reflex pupillary dilatation in response to noxious stimulation. The relationship between the target effect site concentration (Ce(T)) of remifentanil and the pupil diameter and reactivity in response to a standard noxious stimulus were evaluated. Anaesthesia was induced with propofol TCI to obtain loss of consciousness (LOC) in 12 ASA I/II patients. Thereafter, remifentanil Ce(T) was titrated by increments of 1 up to 5 ng ml(-1). In the awake state, at LOC and at each plateau level of remifentanil Ce(T), arterial pressure, heart rate, and BIS (A2000) were recorded. Pupil size and dilatation after a 100 Hz tetanic stimulation (T100) were measured at LOC and at each plateau level of remifentanil Ce(T). LOC was observed at a mean propofol Ce(T) of 3.53 (SD 0.43) microg ml(-1). Arterial pressure and heart rate decreased progressively from LOC to 5 ng ml(-1) remifentanil Ce(T) without any statistical difference between each incremental dose of remifentanil. Mean BIS values decreased from 96 (2) in the awake state, to 46 (12) at LOC (P<0.05) and then remained unchanged at all remifentanil Ce(T). Pupil dilatation in response to 100 Hz tetanic stimulation decreased progressively from 1.55 (0.72) to 0.01 (0.03) mm and was more sensitive than pupil diameter measured before and after 100 Hz tetanus. An inverse correlation between pupil dilatation in response to 100 Hz tetanus and an increase in remifentanil Ce(T) from 0 to 5 ng ml(-1) was found (R(2)=0.68). During propofol TCI in healthy patients, the decrease in pupil response to a painful stimulus is a better measurement of the progressive increase of remifentanil Ce(T) up to 5 ng ml(-1) than haemodynamic or BIS measurements.

Supraspinal pupillary effects of intravenous and epidural fentanyl during isoflurane anesthesia

Epidural fentanyl has been shown to gain rapid access to the circulation resulting in supraspinal effects. We compared the supraspinal effects of fentanyl via epidural versus intravenous (IV) routes, during isoflurane anesthesia. Supraspinal fentanyl effect was evaluated as a reduction of pupillary reflex dilation (PRD) measured with infrared pupillometry. Eighteen patients undergoing abdominal procedures were studied during combined epidural and general anesthesia. General anesthesia was provided by 0.55 to 0.70% end-tidal isofurane in air:oxygen (50:50). Sensory block of the surgical field was established with bupivacaine 0.375% and confirmed by absence of PRD to cutaneous stimulation. A high cervical dermatome was then stimulated (60 to 70 mA) at 5-minute intervals via cutaneous needle electrodes, and PRD was measured with each stimulation, using infrared pupillometry. Baseline PRD was determined and then a randomized injection of cpidueral saline (n = 6), epidural fentanyl 3 microg/kg (n = 6), or IV fentanyl 3 microg/kg (n = 6) was given. Subsequently, PRD was measured at 5, 10, 20, 30, 40, 60, and 80 minutes. Maximum change in PRD and time to maximum change were calculated for each group. Following epidural injection, suppression of PRD was highly variable among subjects. The maximum suppression was 70+/-15% at 23.3+/-10.3 minutes for the epidural group and 96+/-3% at 10.8+/-7.4 min for the IV group (P<.0001). Epidural saline produced no effect. Supraspinal effects of epidural fentanyl can be assessed during general anesthesia using infrared pupillometry. Epidural fentanyl 3 microg/kg produces significant but variable supraspinal effects during 0.5 minimum alveolar concentration isoflurane anesthesia.

Lidocaine does not depress reflex dilation of the pupil

Pupillary dilation in response to dermatomal electrical stimulation is one method of determining sensory block level during combined epidural and general anesthesia. Use of this technique may, however, be confounded by systemic absorption of epidurally administered local anesthetics. Accordingly, the effects of intravenous lidocaine on the magnitude and duration of reflex pupillary dilation were evaluated. Six volunteers were each anesthetized twice with desflurane 3.5-6.0%. During one anesthetic, intravenous lidocaine was administered to a plasma concentration of 5.3 +/- 1.5 micrograms/mL. When the plasma concentrations were stable, a 5-second tetanic electrical stimulus was applied. Pupil size was then recorded for 8 minutes. Lidocaine, at plasma concentrations near 5 micrograms/mL, did not significantly alter the pupillary response to electrical stimulation. In contrast, stimulus-induced increase in heart rate was obliterated. Painful stimulation did not increase systolic blood pressure in either case. Typical plasma lidocaine concentrations observed during epidural anesthesia are unlikely to prevent the use of pupillary responses to evaluate sensory block level.

Sympathetic nervous system does not mediate reflex pupillary dilation during desflurane anesthesia.

Pupil size is determined by an interaction between the sympathetic and parasympathetic divisions of the autonomic nervous system. Noxious stimulation dilates the pupil in both unanesthetized and anesthetized humans. In the absence of anesthesia, dilation is primarily mediated by the sympathetic nervous system. In contrast, pupillary dilation in cats given barbiturate or cloralose anesthesia is mediated solely by inhibition of the midbrain parasympathetic nucleus. The mechanism by which noxious stimuli dilate pupils during anesthesia in humans remains unknown. Accordingly, the authors tested the hypothesis that the pupillary dilation in response to noxious stimulation during desflurane anesthesia is primarily a parasympathetic reflex. In six volunteers, the alpha-I adrenergic receptors of the iris musculature were blocked by unilateral administration of topical dapiprazole; six other volunteers were given unilateral topical tropicamide to block the muscarinic receptors in the iris. Desflurane anesthesia was subsequently induced in all volunteers. Sympathetic nervous system activation, with reflex dilation of the pupil, was produced by noxious electrical stimulation during 4% and 8% end-tidal desflurane, and by a rapid 4%-to-8% step-up in the desflurane concentration. Pupil diameter and the change in pupil size induced by a light stimulus (light reflex amplitude) were measured with infrared pupillometry. Dapiprazole drops produced a Horner's miosis, but pupils were equally small after induction of anesthesia. Pupillary dilation after noxious stimulation and desflurane step-up was identical in the unblocked and dapiprazole-blocked pupils. After tropicamide administration, the pupil was dilated and the light reflex was completely inhibited. Noxious stimulation nonetheless produced a slight additional dilation. During desflurane anesthesia, pupillary dilation in response to noxious stimulation or desflurane step-up is not mediated by the sympathetic nervous system (as it is in unanesthetized persons). Although inhibition of the pupillo-constrictor nucleus may be the cause of this dilation, the mechanism remains unknown.

Alpha 1- and alpha 2-adrenoreceptor antagonists produce opposing mydriatic effects by a central action.

1. In anaesthetized rats, intravenous administration of alpha 2-adrenoreceptor antagonists yohimbine (0.3-3.0 mg kg-1), idazoxan (0.03-0.3 mg kg-1) and raulwolscine (0.3-3.0 mg kg-1) produced a dose-related inhibition of sciatic nerve-(ScN) mediated reflex pupillary dilation (parasympatho-inhibition). The rank order of potency was idazoxan greater than yohimbine greater than rauwolscine. 2. Under similar experimental conditions, intravenous administration of alpha 1-adrenoreceptor antagonists prazosin (0.03-1.0 mg kg-1), phenoxybenzamine (0.3-3.0 mg kg-1) and corynanthine (0.03-1.0 mg kg-1) produced a dose-dependent potentiation of the reflex mydriasis with the potency order being prazosin greater than corynanthine greater than phenoxybenzamine. Intravenous yohimbine (1.5 mg kg-1) reversed the potentiation caused by the alpha 1-adrenoreceptor antagonists and blocked the reflex mydriasis. 3. Parasympatho-inhibition and mydriasis elicited by hypothalamic stimulation was not affected by the alpha 2-adrenoreceptor antagonists yohimbine (0.3-3.0 mg kg-1), idazoxan (0.03-0.3 mg kg-1) or the alpha 1-adrenoreceptor antagonist prazosin (0.3-1.0 mg kg-1). 4. Microinjection of prazosin (3-30 ng) into the oculomotor nuclear complex (IIIn), produced a dose-related potentiation, whereas microinjection of yohimbine (0.3-3.0 micrograms) produced a dose-related blockade of reflex mydriasis. 5. The above findings support the hypothesis that ascending mechanisms (e.g. afferent ScN) produce inhibition of parasympathetic oculomotor tone to the iris by activation of central postsynaptic alpha 2-adrenoreceptors. Furthermore, these studies demonstrate that alpha 2-adrenoreceptor antagonists block and alpha 1-adrenoreceptor antagonists potentiate the reflex mydriasis. These actions appear to be localized within the pupilloconstrictor regions of the brain (oculomotor nuclear complex).

The origin and physio-pharmacological properties of the humoral factor in the reflex pupillary dilation: An experimental study in the cat

The origin and physio-pharmacological properties of the humoral factor in the reflex pupillary dilation: An experimental study in the cat

Effects of stimulus omission during habituation of the pupillary dilation reflex

The pupillary dilation reflex of the paralyzed cat was studied during habituation to an acoustic stimulus. The effect of a scheduled stimulus omission was assessed by examination of pupillary activity during the omission, in the 4-sec intertrial interval, and on the following trial. It was found that dilation responses during the omission were rare. Effects were seen more often in the intertrial interval or on the following trial (“dishabituation”). Responses to an omitted stimulus were related to the dynamics of background (“tonic”) pupillary size; specifically, they occurred significantly more often for subjects which exhibited an increase in background pupillary diameter following initial stimuli and then a decrease during the later course of habituation.

Pupillodilator pathways in the brain stem of the cat: Anatomical and electrophysiological identification of a central autonomic pathway

Three pupillodilator pathways have been identified in the brain stem of the cat by means of electrical stimulation with microelectrodes. 1. (1) A descending, excitatory pathway which projects to the intermediolateral cell column (C8-T2) has been identified in the ventrolateral tegmentum. This pathway has been traced at successively caudal levels. It lies dorsolateral to the medial lemniscus at the collicular and pontine levels and next to the spinothalamic tract. At more caudal levels, the pathway moves to a position dorsolateral to the pyramidal tract. In the cervical spinal cord, it shifts to a superficial position in the lateral funiculus near the insertion zone of the dentate ligament. Axon degeneration studies confirm these results and indicate that very few fibers from the tegmentum reach the spinal cord directly. This pathway projects primarily in an ipsilateral manner. Some of the axons cross in the dorsal commissure of the spinal cord at the C8-T2 levels to reach the contralateral side. 2. (2) An ascending inhibitory pathway projecting to the Edinger-Westphal nucleus has been identified in the paramedian reticular formation of the medulla and pons. This pathway has been traced rostrally through the medial tegmental reticular formation in an area dorsal to the medial lemniscus. At rostral levels, it lies lateral to the interpeduncular nucleus. 3. (3) An ascending inhibitory pathway has been found to be associated with the lateral pupillodilator pathway. It seems probable that this system is involved in nociceptive reflex pupillary dilatation. Whether this pathway is part of the spinothalamic tract or is a separate pathway has not been settled.

Effect of vestibular stimulation on pupillary size

The action of utricular stimulation on ocular reflexes has been examined with particular attention to the effects upon autonomic outflow and intraocular muscle activity. Brisk, conjugate deviations of the eyes in response to single air puff stimulation, in both cats and monkeys, were accompanied by pupillary reactions, constriction during the fast phase of eye movement, and dilatation during the slow phase. During the nystagmus obtained in monkeys and evoked by an air jet directed at the utricle, the pupils showed initially a strong dilatation with superimposed, rapid, minor constrictions of a random frequency. After the end of stimulation and at the occurrence of a secondary nystagmus, there was a dilatation during the fast phase and constriction during the slow. As the nystagmus gradually diminished, the pupils concomitantly returned to control size and ceased to fluctuate. Prolonged stimulation gave rise to an increased stream of efferent impulses in sympathetic fibers to the eye in synchrony with pupillary dilatation while the activity of ciliary nerves showed a simultaneous decrease. However, anatomical integrity of the sympathetic connections is not a prerequisite for the presence of these pupillary reactions to vestibular stimulation since their sectioning did not change the effect. Thus, the results of these experiments substantiate the conclusion previously reached that reflex pupillary dilatation can be accomplished by pure inhibition of parasympathetic tone.

Analysis of cerebral control of reflex pupillary dilation in cat and monkey.

THE PATHOGENESIS of inequality of the pupils following cerebral trauma is controversial. In 1878 Hutchinson described the unilaterally dilated fixed pupil in victims of head trauma. 1 He suggested impairment of the oculomotor nerve as the causative factor, and subsequent workers suggested the same etiological mechanism. 2 However, this explanation is not always applicable. In over two-thirds of a series of 450 cases of head trauma studied, the unilateral dilated pupil reacted well to a light stimulus, indicating that the oculomotor nerve was not completely functionless; furthermore, subsequent necropsy revealed no gross or microscopic damage to the oculomotor nerve. 3 Other observations suggested a cerebral mechanism. 3 Several investigators have studied cerebral effects on the pupil from the physiological standpoint. Pupillary dilation in animals following cerebral electrical stimulation was reported first by Bochefontaine. 4 Soon thereafter substantiating observations appeared. 5 By 1900 Sherrington's work on dogs and revealed that pupillary