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Parasympathetic Mediated Pupillary Dilation Elicited by Lingual Nerve Stimulation in Cats

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Parasympathetic Mediated Pupillary Dilation Elicited by Lingual Nerve Stimulation in Cats Parasympathetic Mediated Pupillary Dilation Elicited by Lingual Nerve Stimulation in Cats Tomohiro Tanaka,1 Satoshi Kuchiiwa,2 and Hiroshi Izumi3 PURPOSE. To determine the autonomic efferent nerve pathways palate, and tongue) and salivary or lacrimal secretions from the for the reflex pupillary dilation elicited by somatic stimulation submandibular, parotid, and lacrimal glands. in cats. During an experimental study on the effects of somatic METHODS. Cats anesthetized with a mixture of ␣-chloralose (50 stimulation on pupil size in urethane-anesthetized cats, we mg/kg) and urethane (100 mg/kg) were intubated and para- found that centrally directed LN stimulation consistently di- lyzed by intravenous injection of pancuronium bromide. The lated the pupil that depended on both stimulus frequency and central cut end of the lingual nerve (LN) was stimulated elec- intensity. This response occurred even though the anesthesia trically to simulate somatic stimulation, and 1 ␮L of lidocaine was deep enough to prevent a reflex elevation of systemic (2%) was microinjected into the Vsp or the EW nucleus to arterial blood pressure (SABP) by a noxious stimulus (e.g., determine its effect on the pupillary dilation induced by LN pinching the upper lip for approximately 2 seconds). Somatic stimulation has long been known to induce a reflex stimulation. The effect of electrically stimulating the Vsp or 12–14 sectioning the superior cervical sympathetic nerve (CSN) on pupillary dilation via the efferent autonomic nerve. How- the pupillary response was also examined. ever, the sympathetic and parasympathetic efferent nerve path- ways for reflex pupillary dilation induced by somatic stimula- RESULTS. Stimulation of the LN or the trigeminal spinal nucleus tion have still not been completely determined, and systematic (Vsp) evoked pupillary dilation in a frequency- and intensity- studies have not been performed to analyze the central or dependent manner. These responses were not affected by peripheral neural pathways involved in the reflex pupil dila- sectioning the ipsilateral or both CSNs. The pupillary responses tion. were markedly suppressed by microinjecting lidocaine into the In this study, we used the changes in pupil size and lip ipsilateral Vsp or the Edinger-Westphal (EW) nucleus, but not blood flow (LBF) elicited by electrically stimulating the central by injection into the contralateral Vsp. cut end of the LN to study the effect of sectioning the superior CONCLUSIONS. These results indicate that the Vsp and EW nu- cervical sympathetic nerve (CSN), or the microinjection of cleus act as bulbar relay centers for pupillary dilation elicited nonselective, reversible local anesthesia (lidocaine) into the by LN stimulation and suggest that the efferent arc of the trigeminal spinal nucleus (Vsp) or the Edinger-Westphal (EW) response is a parasympathetic pathway. The contralateral pu- nucleus on the pupillary dilation. The EW nuclei are known to pillary dilation appears to be mediated, at least in part, by fibers send the preganglionic parasympathetic axons with the oculo- projecting from the Vsp to the contralateral EW nucleus. (In- motor nerve to the iris. vest Ophthalmol Vis Sci. 2005;46:4267–4274) DOI:10.1167/ The purpose of this study was to examine the central and iovs.05-0088 peripheral efferent pathways of the pupillary dilation and in- crease in the LBF and to determine whether they are sympa- e have reported that electrical stimulation of the central thetic or parasympathetic pathways. The cat was selected Wcut end of a branch of the trigeminal nerve (e.g., the because its pupil is constricted under ␣-chloralose-urethane lingual nerve [LN], or the tooth pulp which is innervated by anesthesia, which enabled us to obtain measurements of the the trigeminal nerve) elicits different responses mediated by reflex pupil dilation. The cat was also used because the reflex parasympathetic reflex mechanisms.1–11 These responses in- arcs for somatoparasympathetic reflex vasodilation in the 15–17 clude vasodilation in the orofacial area (e.g., lower lip, gingiva, lower lip have been well defined. METHODS From the 1Department of Ophthalmology, Tohoku University School of Medicine, Miyagi, Japan; the 2Department of Neuroanatomy, Preparation of Animals Field of Neurology, Kagoshima University Graduate School of Medical The procedure used adhered to the guidelines of the ARVO Statement 3 and Dental Sciences, Kagoshima, Japan; and the Department of Oral for the Use of Animals in Ophthalmic and Vision Research and were Physiology, School of Dentistry, Health Sciences University of Hok- approved by the Committee of Animal Experimentation, Tohoku Uni- kaido, Hokkaido, Japan. versity School of Medicine. Supported in part by Grant-in-Aid 15591962 from the Ministry of Fourteen adult cats approximately 2 to 4 years of age and of both Education, Culture, Sports, Science and Technology of Japan (HI); funding from the Akayama Foundation (HI); and, from the Ministry of sexes were used. The cats, weighing 2.5 to 4.8 kg, were initially Education, Culture, Sports, Science, and Technology, which provided sedated with ketamine hydrochloride (30 mg/kg intramuscularly) and a matching fund subsidy from the High-Tech Research Center Project anesthetized with a mixture of ␣-chloralose (50 mg/kg) and urethane for Private Universities. (100 mg/kg). A femoral artery was cannulated for the measurement of Submitted for publication January 25, 2005; revised June 8, 2005; SABP. The anesthetized animals were intubated and paralyzed by an accepted September 9, 2005. initial intravenous (IV) injection of 0.4 mg/kg pancuronium bromide Disclosure: T. Tanaka, None; S. Kuchiiwa, None; H. Izumi, (Mioblock; Organon, Teknika, The Netherlands). The paralysis was None maintained by supplements of 0.2 mg/kg approximately every hour The publication costs of this article were defrayed in part by page charge payment. This article must therefore be marked “advertise- after testing the level of anesthesia. The animals were artificially ven- ment” in accordance with 18 U.S.C. §1734 solely to indicate this fact. tilated with a mixture of 50% air and 50% O2. The ventilator (model Corresponding author: Hiroshi Izumi, Department of Oral Physi- SN-480-6; Shinano, Tokyo, Japan) was set to deliver a tidal volume of 10 ology, School of Dentistry, Health Sciences University of Hokkaido, to 12 cm3/kg at a rate of 20 breaths/min, and the end-tidal concentra- Ishikari-Tobetsu, Hokkaido 061-0293, Japan; [email protected]. tion of CO2 was determined by an infrared analyzer (Capnomac Ultima; Investigative Ophthalmology & Visual Science, November 2005, Vol. 46, No. 11 Copyright © Association for Research in Vision and Ophthalmology 4267 Downloaded from iovs.arvojournals.org on 09/25/2021 4268 Tanaka et al. IOVS, November 2005, Vol. 46, No. 11 Datex Co., Helsinki, Finland) and kept at 35 to 40 mm Hg. The rectal temperature was maintained at 37°C to 38°C with a heating pad. The criterion for an adequate depth of anesthesia was the absence of any significant changes in SABP as reflex responses to a minor noxious stimulus (e.g., a pinch of the upper lip for approximately 2 seconds). If the depth of anesthesia was considered inadequate, addi- tional ␣-chloralose and urethane were administered intravenously in doses of 5 and 10 mg/kg, respectively. Once an adequate depth of anesthesia was attained, supplemental doses of pancuronium were given approximately every 60 minutes to maintain immobilization during periods of stimulation. Isolation and Electrical Stimulation of the CSN An operating microscope (OME; Olympus, Tokyo, Japan) was used for the isolation of the CSN from the vagosympathetic nerve bundle, for the insertion of a bipolar electrode into the peripheral cut end of the isolated nerve, and for the insertion of a guide cannula into the Vsp or EW nucleus. The CSN was excited electrically with a stimulator (model SEN-7103; Nihon Kohden, Tokyo, Japan) for 20-second trains (10 V, 0.1–100 Hz, 2-ms pulse duration). Measurements of Pupil Size Photographs of pupils were taken with a digital camera (EOS D60; Canon, Tokyo, Japan). A millimeter scale was placed on the forehead of the cat to measure the pupil size. Photographs were taken from 25 FIGURE 1. Schematic representation of electrical stimulation, blood to 30 cm, which was the nearest distance at which both pupils could flow measurements, and microinjection of lidocaine. The stimulation be viewed on one screen. The photographs were taken before and sites were the central cut end of the LN (A) and the Vsp (B). The blood flow measurement site was the lower lip (C) by laser-Doppler flowme- immediately after the stimulation for each stimulus condition. ter. Microinjection sites were the Vsp (B) and the EW nucleus (D). P, The photographs were analyzed by the NIH image program (avail- pupil; CG, ciliary ganglion; OG, otic ganglion; ISN, inferior salivatory able by ftp at zippy.nimh.nih.gov/ or at http://rsb.info.nih.gov/nih- nerve; c, contralateral. image; developed by Wayne Rasband, National Institutes of Health, Bethesda, MD). The areas of pupils were outlined manually on a personal computer, and sizes were calculated automatically in pixels. the brain. A concentric bipolar electrode (Inter Medical, Tokyo, Japan), The pupillary areas were then converted into millimeters by using the insulated with enamel except at the tip, was inserted through the scale that had been calibrated in pixels. We calculated and plotted the guide cannula. The electrode was positioned in the Vsp by lowering changes in pupillary size as the size after the stimulation minus the size the stimulating electrode while delivering electrical stimulation and before the stimulation. stopping when the maximum pupillary response was elicited. Small vertical movements of the stimulating electrode (e.g., 0.5 mm) often Measurements of LBF and SABP markedly reduced the responses, indicating that current spread from Changes in the blood flow in the lower lip were measured with a laser the electrode tip was not excessive.
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