PAG SD n 30 VPL 12 LSTT PAG/NRD 1 0.5ml PAG LSTT VPL n 18 PAG n 5 n 5 PAG/NRD Key words acupuncture analgesia radiant heat stimulation asce
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1 PAG SD n 30 VPL 12 LSTT PAG/NRD 10.5mlPAG LSTT VPL n 18PAG n 5 n 5 PAG/NRD Key words acupuncture analgesia radiant heat stimulation ascending inhibitory pathway ventral posterolateral nucleus periaqueductal gray matter Received October 31, 2012; Accepted December 27, 2012 I descending pain inhibitory systemdiffuse noxious inhibitory controlsdnic Tel: c_ogasawara@meiji-u.ac.jp Melzack Wall Reynolds periaqueductal gray matter PAG 3 Mayer PAG 4 PAG 5 7 Basbaum PAG dorsolateral funiculusdlf
2 24 The Bulletin of Meiji University of Integrative Medicine 8 PAG nucleus raphe dorsalis NRD 9,10 Horie PAG NRD ventral posterolateral nucleusvpl nociceptive specific NSwide dynamic range WDR PAG/NRD 11 VPL lateral spinothalamic tractlstt VPL II Sprague-Dawley g ml 1.2g/kg AP-641GAT-601G ST-7 1cm mg/kg MODELSN ml air/kg 90cycle/min MK g/h0.07g/h KDS VPL Pontamine Sky Blue20.5M 1.5mm 911MW PC-5N 10mm mm mm 4,0006,000mm DAM-80 WPIUSAVC-11 XR-30 TEACAD-100F AD Micro DSE-325P 1
3 5 0.18mm PF5-1 5mm LSTT Low threshold mechanoreceptiveltm mm mm WDR NS VPL LSTT Duration 200msec 3 VPL 14,15 3 LSTT 30mm 0.3mm mm 5 5mm mg 5 2 3mm 47 LSTT 5 n 22 30mm 0.3mm 6PAG/NRD 15 PAG/NRD 10mm 5mm 30 VPL 1 LSTT VPL PAG/NRD ml 3mm 47 AMI-X AG-70 SM-25A 5VPL LSTT 7.6mm mm VPL WDR 20 NS LSTT 5,0005,500mm 12 Th12 10mlUSA Th12 Th11 IC-3100 Th13 0.1ml/ 0.5ml 1 LSTT VPL 25
4 26 The Bulletin of Meiji University of Integrative Medicine 1VPL WDR A A A BB AA 1 C D VPL PAG 5 5 GraphPad Prism 5JGraphPad Software USA PAG/NRD III 7 1VPL Pontamine Sky Blue 2mADC 30 VPL mADC DTK-100 EM mm Cresyl violet 20 LTM n 20 WDR 1n 57NS 2n 9 PAG/NRD WDR NS 12 8 LTMWDRNS Bonferroni 5
5 2VPL NS A A A BB AA 1 C D VPL 27 VPL 2VPL LSTT 12 LSTT VPL 12 LSTT NS n 22 3 LSTT VPL WDR NS msec 10.2ms 2ms 2.0ms 40330mA 156.4mA 4 LSTT 50Hz 5G 3VPL 12 LSTT VPL VPL VPL /sec /sec
6 28 The Bulletin of Meiji University of Integrative Medicine 3 12 LSTT 12 LSTT A 12 LSTT B C D C 1 LSTT NS vs vs P Bonferroni vs P SD SD SD P LSTT VPL 12 LSTT Duration200msec vs 30mA VPL vs P Bonferroni 10 vs P ms 2ms /sec /sec 4 15 /sec /sec 2 VPL 6A 25 5 LSTT SD SD SD P VPL PAG/NRD LSTT VPL PAG/NRD 5 1 VPL 5 79 PAG 5
7 A B VPM VPL C D E F E F G * * * * * * * * * * * * 10 (Hz) VPL A LSTT 30mA VPL B C LSTT D VPL E E E FF EE 1 G LSTT 50Hz VPL VPL WDR VPM ventral posteromedial nucleus VPL ventral posterolateral nucleus 810 6B PAG/NRD IV 1VPL VPL VPL MRI PET VPL
8 30 A B VPM VPL PAG VPM VPL NRD VPM VPL The Bulletin of Meiji University of Integrative Medicine 2mm 10mm 6VPL PAG/NRD A LSTT VPL n 25n 18 n PAG/NRD 5 B PAG/NRD 0.5ml n 5n 5PAG periaqueductal gray matter NRD nucleus raphe dorsalis NS Francis 18 WDR 2 WDR NS NS Matsushita 17 WDR 13 2 VPL WDR NS VPL 2VPL LSTT Guilbaud 14 VPL LSTT I LSTT IIIIV VPL LSTT VPL LSTT NS
9 A 1 B VPM VPL C D 31 7PAG/NRD VPL A PAG LSTT 30mA VPL B C LSTT D PAG/NRD PAG/NRD VPL VPL NS WDR LSTT VPL VPL 30 VPL VPL
10 32 A 1 B VPM VPL The Bulletin of Meiji University of Integrative Medicine C D 8PAG/NRD VPL A LSTT 45mA VPL B C LSTT D PAG/NRD VPL 1 5 VPL C Ad 1 15 VPL C Ad 1 1
11 A 1 B VPM VPL C D 33 9PAG/NRD VPL A PAG LSTT 30mA VPL B C LSTT D PAG/NRD PAG/NRD VPL 1 5 VPL ms 10.2ms 4 50Hz 5G VPL LSTT VPL VPL LSTT LSTT VPL 3 VPL PAG/NRD VPL PAG/NRD PAG/NRD PAG/ NRD PAG /NRD 21 23
12 34 A 1 B VPM VPL The Bulletin of Meiji University of Integrative Medicine C D 10PAG/NRD VPL A LSTT 45mA VPL B C LSTT D PAG/NRD VPL ml PAG /NRD PAG/NRD VPL 1 PAG/NRD VPL Barbaresi PAG VPL 24 Horie PAG NRD VPL 11 PAG NRD
13 PAG/NRD 25 subnucleus reticularis dorsalissrd 28 VPL PAG/NRD VPL 29 30,31 4 PAG/NRDNRMNRPGLC Ab PAG 11,16,17 DNIC VPL 42 DNIC LSTT DNIC 1 15 C Ad PAG NRDnucleus raphe PAG magnusnrmnucleus reticularis paragigantocellularisnrpgnucleus VPL reticularis gigantocellularisnrgclocus ceruleuslc VPL PAG VPL 10,26 VPL 9,27 PAG VPL GABA 43 C Ad DNIC 35
14 36 The Bulletin of Meiji University of Integrative Medicine 5 VPL 44 9,20 9 VPL 45 V VPL VPL LSTT PAG/NRD 1 VPL 106 LTM 20 WDR 57 NS VPL LSTT VPL PAG/ NRD n 5 PAG/NRD n 5 PAG/NRD VPL (6): , Melzack R, Wall PD: Pain mechanisms: a new theory. Science, 150: , Reynolds DV: Surgery in the rat during electrical analgesia induced by focal brain stimulation. Science, 164: , Mayer DJ, Wolfle TL, Akil H, et al: Analgesia from electrical stimulation in the brainstem of the rat. Science, 174: , Adams JE: Naloxone reversal of analgesia produced by brain stimulation in the human. Pain, 2: , Richardson DE, Akil H: Pain reduction by electrical brain stimulation in man: part 1 acute administration in periaqueductal and periventricular sites. J Neurosurg, 47: , Hosobuchi Y, Adams JE, Linchitz R: Pain relief by electrical stimulation of the central gray matter in humans and its reversal by naloxone. Science, 197: , Basbaum AI, Fields HL: The origin of descending
15 pathways in the dorsolateral funiculus of the spinal cord of the cat and rat: further studies on the anatomy of pain modulation. J Comp Neurol, 187(3): , , Helmstetter FJ, Tershner SA, Poore LH, et al: Antinociception following opioid stimulation of the basolateral amygdala is expressed through the periaqueductal 9. 2 pp 71-90, gray and rostral ventromedial medulla. Brain Res, 779(1-2): , Koyama N, Hanai F, Yokota T: Does intravenous 10. 8(2): , Horie H, Pamplin PJ, Yokota T: Inhibition of nociceptive neurons in the shell region of nucleus ventralis posterolateralis following conditioning stimulation of the periaqueductal grey of the cat. Evidence for an ascending inhibitory pathway. Brain Res, 561(1): 34-42, Paxinos G, Watson C: The Rat Brain in Stereotaxic Coordinates, 4th edn. Academic Press, California, Yokota T, Asato F, Koyama N et al: Nociceptive body representation in nucleus ventralis posterolateralis of cat thalamus. J Neurophysiol, 60(5): , Guilbaud G, Peschanski M, Gautron M, et al: Neurones responding to noxious stimulation in VB complex and caudal adjacent regions in the thalamus of the rat. Pain, 8(3): , Yokota T, Koyama N, Matsumoto N: Somatotopic distribution of trigeminal nociceptive neurons in ventrobasal complex of cat thalamus. J Neurophysiol, 53(6): , Koyama N, Nishikawa Y, Chua AT et al: Differential inhibitory mechanisms in VPL versus intralaminar nociceptive neurons of the cat: I. Effects of periaqueductal gray stimulation. Jpn J Physiol, 45(6): , Matsushita M, Kizuki N, Koyama N: Exitatory and inhibitory effects of vagal afferent input on nociceptive neurons in the nucleus ventralis posterolateralis of the cat thalamus. J Shiga Univ Med Sci, 11: , Francis JT, Xu S, Chapin JK: Proprioceptive and cutaneous representations in the rat ventral posterolateral thalamus. J Neurophysiol, 99(5): , Kuru M: Sensory Paths in the Spinal Cord and Brain Stem of Man, Sogensha, Tokyo, pp 1-39, (7): 533- administration of GABA(A) receptor antagonists induce both descending antinociception and touchevoked allodynia? Pain, 76(3): , Oliveira MA, Prado WA: Role of PAG in the antinociception evoked from the medial or central amygdala in rats. Brain Res Bull, 54(1): 55-63, Barbaresi P, Conti F, Manzoni T: Periaqueductal grey projection to the ventrobasal complex in the cat: an horseradish peroxidase study. Neurosci Lett, 30(3): , : 39, (5): , Fields HL, Basbaum AI: Endogenous pain control mechanisms. In Wall PD, Melzack R (eds): Textbook of pain. Churchill Livingstone, New York, pp , Bouhassira D, Villanueva L, Bing Z, et al: Involvement of the subnucleus reticularis dorsalis in diffuse noxious inhibitory controls in the rat. Brain Res, 595: , Le Bars D, Dickenson AH, Besson JM: Diffuse noxious inhibitory controls (DNIC). I. effect on dorsal horn convergent neurons in the rat. Pain, 6: , Bing Z, Villanueva L, Le Baes D: Acupuncture and diffuse noxious inhibitoru controls: naloxonereversible depression of activities of trigeminal convergent neurons. Neuroscience, 37: , Dickenson AH, Rivot JP, Chaouch A, et al: Diffuse noxious inhibitory controls (DNIC) in the rat with or without pcpa pretreatment. Brain Res, 216(2): , Bouhassira D, Villanueva L, Le Bars D: Effects of systemic morphine on diffuse noxious inhibitory controls: role of the periaqueductal grey. Eur J Pharmacol, 216(2): , Bouhassira D, Chitour D, Le Bars D, et al: Morphine 37
16 38 The Bulletin of Meiji University of Integrative Medicine and diffuse noxious inhibitory control in the rat: effects of lesions of the rostral ventromedial medulla. Eur J Pharmacol, 232: , Bouhassira D, Bing Z, Le Bars D: Studies of brain structures involved in diffuse noxious inhibitory controls in the rat: the rostral ventromedial medulla. J Physiol, 463: , Bouhassira D, Bing Z, Le Bars D: Effects of lesion of locus coeruleus/subcoeruleus on diffuse noxious inhibitory controls in the rat. Brain Res, 571: , Lewis JW, Sherman JE, Liebeskind JC: Opioid and non-opioid stress analgesia: assessment of tolerance and cross-tolerance with morphine. J Neurosci, 1(4): , Maier SF, Drugan RC, Grau JW: Controllability, coping behavior, and stress-induced analgesia in the rat. Pain, 12(1): 47-56, Watkins LR, Mayer DJ: Organization of endo genous opiate and nonopiate pain control systems. Science, 216(4551): , (3): , : 31-41, Goldman N, Chen M, Fujita T, et al: Adenosine A1receptors mediate local anti-nociceptive effects of acupuncture. Nat Neurosci, 13(7): , Monconduit L, Lopez-Avila A, Molat JL, et al: Corticofugal output from the primary somatosensory cortex selectively modulates innocuous and noxious inputs in the rat spinothalamic system. J Neurosci, 26(33): , Koyama N, Yokota T: Inhibition of activities of VPL nociceptive neurons by dorsal column stimulation. Pain Res, 9: 77-86, Guilbaud G, Kayser V: The ventrobasal complex of the rat thalamus: its involvement in the sensorydiscriminative aspects of nociception, including models of clinical pain. Thalamus and Pain, Elsevier Science Publishers, pp , VIII 2 pp , 1983.
17 Inhibitory effects of nociceptive neurons in the ventral posterolateral nucleus by acupuncture and indirect moxibustion stimulation. Evidence for an ascending inhibitory pathway of acupuncture analgesia Chie Ogasawara, Hiroshi Taniguchi, Hisashi Shinbara, Kokoro Hino, Eiji Sumiya Department of Basic of Acupuncture and Moxibustion, Meiji University of Integrative Medicine ABSTRACT Introduction: Acupuncture and moxibustion have been used to treat diseases with pain. Recently, it has been demonstrated that an ascending inhibitory pathway inhibits pain transmission at the thalamus via neural activity from the periaqueductal gray matter (PAG) to the thalamus. The purpose of this study was to clarify the involvement of this ascending inhibitory pathway in acupuncture and/or moxibustion analgesia. We investigated whether evoked potentials of nociceptive neurons in the ventral posterolateral nucleus (VPL) were inhibited by acupuncture or radiant heat stimulation (similar to indirect moxibustion). Moreover, we examined whether the PAG participated in this inhibitory effect. Methods: Experiments were conducted on rats anesthetized with urethane (n=30). Single unit activities were recorded in the VPL with glass microelectrodes filled with 2% Pontamine sky blue in 0.5 M sodium acetate. The evoked potentials of VPL nociceptive neurons were evoked by electrical stimulation to the spinothalamic tract (LSTT) at Th12. Acupuncture (0.3 mm diameter) or radiant heat stimulation by a incense stick with the fire like the stick moxibustion was applied to the various points of the body while recording the evoked potentials. Further, the same experiments were conducted with microinjections of lidocaine (1%, 0.5 ml; n=5) or saline (n=5) into the PAG. Results: The evoked potentials of VPL nociceptive neurons evoked by electrical stimulation to the LSTT were inhibited by acupuncture or radiant heat stimulation to various points of the whole body except the receptive fields (n=18). These antinociceptive effects were abolished by lidocaine microinjections into the PAG (n=5), but not by saline microinjections (n=5). Conclusion: These results suggest that the ascending inhibitory pathway from the PAG to the thalamus may be involved in acupuncture and moxibustion analgesia. 39
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