title: Stimulation of the ventral tegmental area increased nociceptive thresholds and decreased spinal dorsal horn neuronal activity in rat.
abstract: Deep brain stimulation has been found to be effective in relieving intractable pain. The ventral tegmental area (VTA) plays a role not only in the reward process, but also in the modulation of nociception. Lesions of VTA result in increased pain thresholds and exacerbate pain in several pain models. It is hypothesized that direct activation of VTA will reduce pain experience. In this study, we investigated the effect of direct electrical stimulation of the VTA on mechanical, thermal and carrageenan-induced chemical nociceptive thresholds in Sprague-Dawley rats using our custom-designed wireless stimulator. We found that: (1) VTA stimulation itself did not show any change in mechanical or thermal threshold; and (2) the decreased mechanical and thermal thresholds induced by carrageenan injection in the hind paw contralateral to the stimulation site were significantly reversed by VTA stimulation. To further explore the underlying mechanism of VTA stimulation-induced analgesia, spinal cord dorsal horn neuronal responses to graded mechanical stimuli were recorded. VTA stimulation significantly inhibited dorsal horn neuronal activity in response to pressure and pinch from the paw, but not brush. This indicated that VTA stimulation may have exerted its analgesic effect via descending modulatory pain pathways, possibly through its connections with brain stem structures and cerebral cortex areas.
authors.affiliation: Department of Psychology, The University of Texas at Arlington, 501 South Nedderman Drive, P. O. Box 19528, Arlington, TX, 76019-0528, USA.
authors.forename: Ai-Ling
authors.initials: AL
authors.lastname: Li
authors.affiliation: Department of Psychology, The University of Texas at Arlington, 501 South Nedderman Drive, P. O. Box 19528, Arlington, TX, 76019-0528, USA.
authors.forename: Jiny E
authors.initials: JE
authors.lastname: Sibi
authors.affiliation: Department of Electronic Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Electrical Engineering, The University of Texas at Arlington, 501 South Nedderman Drive, P. O. Box 19528, Arlington, TX, 76019-0528, USA.
authors.forename: Jung-Chih
authors.initials: JC
authors.lastname: Chiao
authors.affiliation: Department of Psychology, The University of Texas at Arlington, 501 South Nedderman Drive, P. O. Box 19528, Arlington, TX, 76019-0528, USA. ypeng@uta.edu.
authors.forename: Yuan Bo
authors.initials: YB
authors.lastname: Peng
mesh_terms: D000698:Analgesia; D000818:Animals; D001522:Behavior, Animal; D005260:Female; D059225:Nociception / Q000502:physiology*; D017288:Pain Threshold / Q000502:physiology*; D020671:Posterior Horn Cells / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017557:Ventral Tegmental Area / Q000502:physiology*
keywords: Analgesia; Dorsal horn; Nociceptive threshold; Ventral tegmental area
references.citation: J Pain. 2008 Jul;9(7):597-605
references.pmid: 18387853
references.citation: Science. 1997 Mar 14;275(5306):1593-9
references.pmid: 9054347
references.citation: Cephalalgia. 2008 Mar;28(3):285-95
references.pmid: 18254897
references.citation: Brain Res. 1997 Mar 14;751(1):1-12
references.pmid: 9098562
references.citation: Methods Mol Biol. 2003;225:115-21
references.pmid: 12769480
references.citation: Cephalalgia. 2011 Dec;31(16):1634-41
references.pmid: 22116943
references.citation: Brain Res. 1996 Oct 14;736(1-2):189-201
references.pmid: 8930324
references.citation: Annu Rev Pharmacol Toxicol. 1980;20:441-62
references.pmid: 7387124
references.citation: Neurosurgery. 1987 Dec;21(6):885-93
references.pmid: 3325851
references.citation: Pain. 2006 Feb;120(3):230-4
references.pmid: 16427195
references.citation: J Pharmacol Exp Ther. 1996 Jul;278(1):125-35
references.pmid: 8764343
references.citation: Trends Pharmacol Sci. 1992 May;13(5):177-84
references.pmid: 1604710
references.citation: Nat Rev Neurosci. 2015 Jun;16(6):316
references.pmid: 25991440
references.citation: Exp Brain Res. 1974 Apr 30;20(1):32-44
references.pmid: 4602289
references.citation: Neurosci Res. 2005 May;52(1):31-6
references.pmid: 15811550
references.citation: Expert Rev Neurother. 2008 May;8(5):781-97
references.pmid: 18457535
references.citation: Mayo Clin Proc. 2012 Oct;87(10):1025-31
references.pmid: 22980165
references.citation: Conf Proc IEEE Eng Med Biol Soc. 2010;2010:1535-8
references.pmid: 21096375
references.citation: Science. 1971 Dec 24;174(4016):1351-4
references.pmid: 5167502
references.citation: Neurosci Lett. 1991 Dec 9;133(2):215-8
references.pmid: 1816499
references.citation: Neurosurgery. 2013 Feb;72(2):221-30; discussion 231
references.pmid: 23149975
references.citation: Proc Natl Acad Sci U S A. 2009 Mar 24;106(12):4894-9
references.pmid: 19261850
references.citation: Exp Brain Res. 1997 May;114(3):561-70
references.pmid: 9187291
references.citation: J Neurosurg. 2007 Jul;107(1):169-72
references.pmid: 17639889
references.citation: Neuroscience. 2014 Mar 28;263:72-87
references.pmid: 24434773
references.citation: Neurosurg Focus. 2006 Dec 15;21(6):E8
references.pmid: 17341052
references.citation: Peptides. 1993 May-Jun;14(3):561-6
references.pmid: 8332552
references.citation: Nat Rev Neurosci. 2008 Apr;9(4):314-20
references.pmid: 18354400
references.citation: Acta Neurochir Suppl (Wien). 1991;52:137-9
references.pmid: 1792954
references.citation: Brain Res. 1973 Feb 28;50(2):441-6
references.pmid: 4705513
references.citation: Pain. 1996 May-Jun;65(2-3):123-67
references.pmid: 8826503
references.citation: Eur J Pharmacol. 2000 Oct 6;406(1):53-8
references.pmid: 11011033
references.citation: Pain. 2006 Nov;125(1-2):188-96
references.pmid: 16797842
references.citation: J Neurosurg. 1985 Mar;62(3):389-96
references.pmid: 3871844
references.citation: Pain. 2007 Nov;132 Suppl 1:S26-45
references.pmid: 17964077
references.citation: J Neurol Sci. 1967 Jul-Aug;5(1):115-20
references.pmid: 6061755
references.citation: Proc Soc Exp Biol Med. 1962 Dec;111:544-7
references.pmid: 14001233
references.citation: Brain Res. 1997 Mar 28;752(1-2):239-49
references.pmid: 9106463
references.citation: Science. 1969 Apr 25;164(3878):444-5
references.pmid: 4887743
references.citation: J Neurosci. 2006 Nov 1;26(44):11501-9
references.pmid: 17079679
references.citation: J Neural Eng. 2012 Oct;9(5):056010
references.pmid: 22955012
references.citation: J Neurosurg. 1977 Aug;47(2):184-94
references.pmid: 301558
references.citation: Brain Res. 2011 Mar 25;1382:189-97
references.pmid: 21295558
references.citation: Cephalalgia. 2013 Jan;33(2):136-8
references.pmid: 23165695
references.citation: J Neurosci. 2015 Sep 2;35(35):12217-31
references.pmid: 26338332
references.citation: Brain Res Rev. 2009 Apr;60(1):214-25
references.pmid: 19146877
references.citation: J Neurosurg. 1977 Aug;47(2):178-83
references.pmid: 327030
references.citation: Pain. 1975 Jun;1(2):139-45
references.pmid: 1088446
references.citation: J Neurophysiol. 2005 Jul;94(1):845-51
references.pmid: 15716373
references.citation: J Physiol. 2006 Dec 15;577(Pt 3):907-24
references.pmid: 16959856
references.citation: Brain Res. 2005 Mar 2;1036(1-2):173-9
references.pmid: 15725415
references.citation: IEEE Trans Neural Syst Rehabil Eng. 2012 Jul;20(4):478-87
references.pmid: 22692935
references.citation: Brain Res Bull. 1982 Jul-Dec;9(1-6):321-53
references.pmid: 6816390
references.citation: J Pharmacol Exp Ther. 1998 Apr;285(1):208-15
references.pmid: 9536012
references.citation: J Pharmacol Exp Ther. 1996 Jan;276(1):116-24
references.pmid: 8558419
references.citation: Annu Rev Neurosci. 2007;30:289-316
references.pmid: 17376009
references.citation: Brain Res. 2005 Sep 28;1057(1-2):134-40
references.pmid: 16122710
references.citation: Brain Res. 2003 Oct 17;987(2):135-43
references.pmid: 14499957
references.citation: Brain Res. 2001 Apr 20;898(2):342-9
references.pmid: 11306021
references.citation: Neurosci Lett. 2015 Jul 10;599:61-6
references.pmid: 26022630
references.citation: Neurosurgery. 2014 Jun;74(6):628-35; discussion 635-7
references.pmid: 24739362
references.citation: Pain. 1988 Jan;32(1):77-88
references.pmid: 3340425
references.citation: Gend Med. 2005 Sep;2(3):137-45
references.pmid: 16290886
references.citation: Acta Neurochir Suppl (Wien). 1980;30:219-27
references.pmid: 6162368
references.citation: Neurol Sci. 2007 May;28 Suppl 2:S138-45
references.pmid: 17508161
references.citation: J Pain. 2009 Jun;10 (6):609-18
references.pmid: 19398377
references.citation: Arch Neurol. 1973 Sep;29(3):158-61
references.pmid: 4591720
references.citation: Nature. 2015 Apr 30;520(7549):675-8
references.pmid: 25925480
references.citation: Neurochirurgie. 1974 Mar-Apr;20(2):117-24
references.pmid: 4418054
references.citation: Pain. 1983 Jun;16(2):109-10
references.pmid: 6877845
references.citation: Brain Res. 1990 Jun 11;519(1-2):144-9
references.pmid: 2118819
references.citation: Proc Natl Acad Sci U S A. 2012 Dec 11;109(50):20709-13
references.pmid: 23184995
references.citation: Neuroscientist. 2004 Jun;10(3):221-34
references.pmid: 15155061
references.citation: J Neurosci Methods. 2008 May 15;170(1):25-34
references.pmid: 18262282
references.citation: J Pain. 2007 Jan;8(1):51-8
references.pmid: 17023218
references.citation: Pain. 2005 Sep;117(1-2):1-5
references.pmid: 16098670
references.citation: Behav Brain Res. 2015 Oct 1;292:508-14
references.pmid: 26166189