AbstractsBiology & Animal Science

Quantification of inhibitory terminals apposing on lamina I spino-parabrachial projection neurons in a rat model of neurpathic pain

by Robert Nahas




Institution: McGill University
Department: Integrated Program in Neuroscience
Degree: MS
Year: 2015
Keywords: Biology - Neuroscience
Record ID: 2060562
Full text PDF: http://digitool.library.mcgill.ca/thesisfile130337.pdf


Abstract

Quantification of inhibitory appositions on pain-processing lamina I parabrachial projection neurons in a rat model of neuropathic painIntroduction: Pain information transmitted by primary afferent fibres from the periphery to the dorsal horn of the spinal cord is modulated by input from local inhibitory and excitatory interneurons and relayed to the brain. A state of reduced inhibition in the spinal cord has been implicated in the pain hypersensitivities associated with neuropathic pain (NP). A recent study from our lab showed a loss of GAD65 (glutamic acid decarboxylase) immunoreactive inhibitory boutons, in the superficial dorsal horn in a rat model of NP. The purpose of this study was to determine if there is a loss of GAD65+ terminals apposing on neurons expressing the substance P receptor (NK1) in lamina I of the dorsal horn which project to the lateral parabrachial nucleus (LPb). Methods: The retrograde tracer choleratoxin B (CTB) was injected into the LPb of male Sprague-Dawley rats that received a unilateral chronic constriction (CCI) or sham injury of the sciatic nerve. Animals were tested weekly for nociceptive hypersensitivities. Horizontal sections of lumbar spinal cord were stained for NK1, CTB and GAD65. Neurons were imaged using a confocal microscope and density of GAD65 appositions was quantified. Results: CCI-operated animals developed mechanical and cold allodynia whereas sham operated controls did not. There was no significant difference between apposition density on NK1r+ lamina I parabrachial projection neurons in neuropathic compared to control animals. Neurons were re-analyzed after being classified into three morphological subclasses: fusiform, multipolar and pyramidal. Pyramidal projection neurons in lamina I had a significantly lower density of inhibitory appositions in cuff- as compared to sham-operated controls. There was no significant difference detected in fusiform or multipolar neurons. Quantification des appositions inhibitrices sur les neurones nociceptifs de projection de la lamina I, dans un modèle de douleur neuropathique chez le ratIntroduction : L'information nociceptive transmise par les fibres afférentes primaires depuis la périphérie vers la corne dorsale de la moelle épinière où elle est modulée localement par des interneurones excitateurs et inhibiteurs puis transmise au cerveau. Un état d'inhibition réduite dans la moelle épinière a été associé aux hypersensibilités nociceptives associées à la douleur neuropathique (NP). Une étude récente de notre laboratoire a montré une perte des boutons inhibiteurs immunoréactifs pour GAD65 (de l'acide glutamique décarboxylase), dans la corne dorsale superficielle dans un modèle de NP chez le rat. Le but de cette étude était de déterminer si une perte de boutons GAD65 positifs en apposition sur les neurones exprimant le récepteur de la substance P (NK1) de la lamina I de la corne dorsale qui se projettent vers le noyau parabrachial lateral (LPb). Méthodes : Le traceur rétrograde CTB (sous-unité B de la toxine cholérique) a été…