마우스 뇌간 부위에서 Kainate 수용체와 TRPV1 수용체의 악안면 통증정보 전달 조절에 미치는 영향에 대한 연구 = Modulation of orofacial nociceptive processing in brainstem; Role of kainate and TRPV1 receptors in the substantia gelatinosa neurons of trigeminal subnucleus caudalis in mice

다국어 초록 (Multilingual Abstract)

Trigeminal primary afferent neurons relay the somatosensory information from the orofacial region to the second-order neurons located in the trigeminal sensory nuclei (Vsn). The Vsn is composed of the mesencephalic nucleus, principal sensory nucleus (Vp) and spinal trigeminal nucleus (Vsp). The Vsp is divided into three subnuclei; oralis (Vo), interpolaris (Vi) and caudalis (Vc). The substantia gelatinosa (SG) of trigeminal subnucleus caudalis (Vc; also called the medullary dorsal horn) receives nociceptive afferent inputs from the thin-myelinated Aδ fibers and unmyelinated C fibers and are implicated in the processing of nociceptive information. Particularly, frequently caused pain in orofacial region involves in various tissue types as tooth, periodontal ligament, and jaw joint. However, mechanism and function of nocice
ptive processing in thetrigeminal subnucleus caudalis (Vc) is little known. Therefore, we investigated the receptors involved in nociceptive processing on SG neurons of mice Vc using electrophysiological and molecular studies; existence and functional response of GluR5 and GluR6 of kainate receptor subunits (KARs) between young and adult and existence of TRPV1 receptor in young. First, mRNA and protein expression of GluR5 and GluR6 subunits were decreased according to developmental maturity in lamina II of mice Vc. Also, KA and GluR5/6 agonists highly show the membrane depolarization on SG neurons of young than adult, suggesting that the change of GluR5 and GluR6 of KA receptor subunits can involve in different pain processing modulation of orofacial regions between young and adult. Second, the TRPV1 receptor expression has been reported in the primary afferent sensory fibers, additionally, we investigated the existence of TRPV1 receptor mRNA on postsynaptic SG neurons in young mice Vc. TRPV1 receptor agonist, capsaicin induced the membrane depolarization and acts directly on young SG neurons. These results suggest that endogenous vanilloid can directly mediate the excitatory response on postsynaptic SG neurons and regulate the nociceptive information of orofacial pain through TRPV1 receptors. In this study, we propose the most prominent potential for therapeutic targets and understanding orofacial pain modulation.

목차 (Table of Contents)

• I. General summary in Korean 1
• II. General abstract 3
• III. General introduction 5
• IV. Reference of general introduction 7
• IV. Subject 1: Developmental changes of GluR5 and GluR6 subunits in the substantia gelatinosa neurons of trigeminal subnucleus caudalis in mice 9
• 1. 국문초록 9
• 2. Abstract 12
• 3. Introduction 14
• 4. Methods and Materials 16
• 5. Results 22
• 6. Discussion 27
• 7. Reference 32
• 8. Figures and Tables 42
• V. Subject 2: Existence of functional TRPV1 receptor on the substantia gelatinosa of trigeminal subnucleus caudalis in mice 55
• 1. 국문초록 55
• 2. Abstract 57
• 3. Introduction 59
• 4. Methods and Materials 61
• 5. Results 65
• 6. Discussion 70
• 7. Reference 75
• 8. Figures and Tables 82
• VI. Achnowledgements 92