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Experimental Brain Research

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01.06.2016 | Research Article

Stimulation of the ventral tegmental area increased nociceptive thresholds and decreased spinal dorsal horn neuronal activity in rat

verfasst von: Ai-Ling Li, Jiny E. Sibi, Xiaofei Yang, Jung-Chih Chiao, Yuan Bo Peng

Erschienen in: Experimental Brain Research | Ausgabe 6/2016

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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.

Altier N, Stewart J (1998) Dopamine receptor antagonists in the nucleus accumbens attenuate analgesia induced by ventral tegmental area substance P or morphine and by nucleus accumbens amphetamine. J Pharmacol Exp Ther 285:208–215PubMed

Ativanichayaphong T, He JW, Hagains CE et al (2008) A combined wireless neural stimulating and recording system for study of pain processing. J Neurosci Methods 170:25–34. doi:10.1016/j.jneumeth.2007.12.014 CrossRefPubMed

Bartsch T, Pinsker MO, Rasche D et al (2008) Hypothalamic deep brain stimulation for cluster headache: experience from a new multicase series. Cephalalgia 28:285–295. doi:10.1111/j.1468-2982.2007.01531.x CrossRefPubMed

Boccard SGJ, Pereira EAC, Moir L et al (2013) Long-term outcomes of deep brain stimulation for neuropathic pain. Neurosurgery 72:221–230. doi:10.1227/NEU.0b013e31827b97d6 CrossRefPubMed

Boccard SGJ, Fitzgerald JJ, Pereira EAC et al (2014) Targeting the affective component of chronic pain: a case series of deep brain stimulation of the anterior cingulate cortex. Neurosurgery 74:628–635. doi:10.1227/NEU.0000000000000321 CrossRefPubMed

Brischoux F, Chakraborty S, Brierley DI, Ungless MA (2009) Phasic excitation of dopamine neurons in ventral VTA by noxious stimuli. Proc Natl Acad Sci USA 106:4894–4899. doi:10.1073/pnas.0811507106 CrossRefPubMedPubMedCentral

Broggi G, Franzini A, Leone M, Bussone G (2007) Update on neurosurgical treatment of chronic trigeminal autonomic cephalalgias and atypical facial pain with deep brain stimulation of posterior hypothalamus: results and comments. Neurol Sci 28:138–145. doi:10.1007/s10072-007-0767-3 CrossRef

Dixon WJ (1980) Efficient analysis of experimental observations. Annu Rev Pharmacol Toxicol 20:441–462CrossRefPubMed

Farajidavar A, Hagains CE, Peng YB et al (2010) Recognition and inhibition of dorsal horn nociceptive signals within a closed-loop system. In: 2010 Annual International Conference of the IEEE Engineering in Medicine and Biology Society EMBC’10, pp 1535–1538. doi:10.1109/IEMBS.2010.5626830

Farajidavar A, Hagains CE, Peng YB, Chiao JC (2012) A closed loop feedback system for automatic detection and inhibition of mechano-nociceptive neural activity. IEEE Trans Neural Syst Rehabil Eng 20:478–487. doi:10.1109/TNSRE.2012.2197220 CrossRefPubMed

Fields HL, Hjelmstad GO, Margolis EB, Nicola SM (2007) Ventral tegmental area neurons in learned appetitive behavior and positive reinforcement. Annu Rev Neurosci 30:289–316. doi:10.1146/annurev.neuro.30.051606.094341 CrossRefPubMed

Gao X, Zhang Y, Wu G (2000) Effects of dopaminergic agents on carrageenan hyperalgesia in rats. Eur J Pharmacol 406:53–58CrossRefPubMed

Gol A (1967) Relief of pain by electrical stimulation of the septal area. J Neurol Sci 5:115–120CrossRefPubMed

Goodman SJ, Holcombe V (1976) Selective and prolonged analgesia in monkey resulting from brain stimulation. In: Bonica JJ, Albe-Fessard DG (eds) Advances in Pain Research and Therapy. Raven Press, New York, pp 495–502

Greenspan JD, Craft RM, LeResche L et al (2007) Studying sex and gender differences in pain and analgesia: a consensus report. Pain. doi:10.1016/j.pain.2007.10.014

Hagains CE, He J-W, Chiao J-C, Peng YB (2011) Septal stimulation inhibits spinal cord dorsal horn neuronal activity. Brain Res 1382:189–197. doi:10.1016/j.brainres.2011.01.074 CrossRefPubMed

Hamani C, Schwalb JM, Rezai AR et al (2006) Deep brain stimulation for chronic neuropathic pain: long-term outcome and the incidence of insertional effect. Pain 125:188–196. doi:10.1016/j.pain.2006.05.019 CrossRefPubMed

Hargreaves K, Dubner R, Brown F et al (1988) A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain 32:77–88CrossRefPubMed

Heath RG, Mickle WA (1960) Evaluation of seven years’ experience with depth electrode studies in human patients. In: Ramey ER, O’Doherty DS (eds) Electrical Studies on the Unanesthetized Brain. P. B. Hoeber, New York, pp 214–247

Heinricher MM, Tavares I, Leith JL, Lumb BM (2009) Descending control of nociception: specificity, recruitment and plasticity. Brain Res Rev 60:214–225. doi:10.1016/j.brainresrev.2008.12.009 CrossRefPubMedPubMedCentral

Hentall ID, Kim JL, Gollapudi L (1991) Responses of neurons in the ventromedial midbrain to noxious mechanical stimuli. Neurosci Lett 133:215–218CrossRefPubMed

Hipolito L, Wilson-Poe A, Campos-Jurado Y et al (2015) Inflammatory pain promotes increased opioid self-administration: role of dysregulated ventral tegmental area opioid receptors. J Neurosci 35:12217–12231. doi:10.1523/JNEUROSCI.1053-15.2015 CrossRefPubMedPubMedCentral

Hosobuchi Y (1980) The current status of analgesic brain stimulation. Acta Neurochir Suppl (Wien) 30:219–227CrossRef

Hosobuchi Y, Adams JE, Rutkin B (1973) Chronic thalamic stimulation for the control of facial anesthesia dolorosa. Arch Neurol 29:158–161. doi:10.1001/archneur.1973.00490270040005 CrossRefPubMed

Kender RG, Harte SE, Munn EM, Borszcz GS (2008) Affective analgesia following muscarinic activation of the ventral tegmental area in rats. J Pain 9:597–605. doi:10.1016/j.jpain.2008.01.334 CrossRefPubMedPubMedCentral

Koob GF (1992) Drugs of abuse: anatomy, pharmacology and function of reward pathways. Trends Pharmacol Sci 13:177–184CrossRefPubMed

Leknes S, Tracey I (2008) A common neurobiology for pain and pleasure. Nat Rev Neurosci 9:314–320. doi:10.1038/nrn2333 CrossRefPubMed

Levy RM, Lamb S, Adams JE (1987) Treatment of chronic pain by deep brain stimulation: long term follow-up and review of the literature. Neurosurgery 21:885–893CrossRefPubMed

Li A, Wang Y, Yang X et al (2012) Stimulation of the ventral tegmental area inhibits spinal cord dorsal horn neuronal activity. In: Annual meeting of the Society for Neuroscience, New Orleans

Liebeskind JC, Guilbaud G, Besson JM, Oliveras JL (1973) Analgesia from electrical stimulation of the periaqueductal gray matter in the cat: behavioral observations and inhibitory effects on spinal cord interneurons. Brain Res 50:441–446. doi:10.1016/0006-8993(73)90748-8 CrossRefPubMed

Ma QP, Zhou Y, Han JS (2000) Noxious stimulation accelerated the expression of c-fos protooncogene in cholecystokininergic and dopaminergic neurons in the ventral tegmental area. Peptides 14:561–566CrossRef

Mallory GW, Abulseoud O, Hwang SC et al (2012) The nucleus accumbens as a potential target for central poststroke pain. Mayo Clin Proc 87:1025–1031. doi:10.1016/j.mayocp.2012.02.029 CrossRefPubMedPubMedCentral

Margolis EB, Lock H, Hjelmstad GO, Fields HL (2006) The ventral tegmental area revisited: is there an electrophysiological marker for dopaminergic neurons? J Physiol 577:907–924. doi:10.1113/jphysiol.2006.117069 CrossRefPubMedPubMedCentral

Mayer DJ, Wolfle TL, Akil H et al (1971) Analgesia from electrical stimulation in the brainstem of the rat. Science 174:1351–1354CrossRefPubMed

Mazars G, Merienne L, Cioloca C (1974) Treatment of certain types of pain with implantable thalamic stimulators. Neurochirurgie 20:117–124PubMed

Messina G, Rizzi M, Cordella R et al (2012) Secondary chronic cluster headache treated by posterior hypothalamic deep brain stimulation: first reported case. Cephalgia 33:136–138. doi:10.1177/0333102412468675 CrossRef

Mogil JS, Chanda ML (2005) The case for the inclusion of female subjects in basic science studies of pain. Pain 117:1–5. doi:10.1016/j.pain.2005.06.020 CrossRefPubMed

Moradi M, Fatahi Z, Haghparast A (2015a) Blockade of D1-like dopamine receptors within the ventral tegmental area and nucleus accumbens attenuates antinociceptive responses induced by chemical stimulation of the lateral hypothalamus. Neurosci Lett 599:61–66. doi:10.1016/j.neulet.2015.05.047 CrossRefPubMed

Moradi M, Yazdanian M, Haghparast A (2015b) Role of dopamine D2-like receptors within the ventral tegmental area and nucleus accumbens in antinociception induced by lateral hypothalamus stimulation. Behav Brain Res 292:508–514. doi:10.1016/j.bbr.2015.07.007 CrossRefPubMed

Morgan MJ, Franklin KB (1990) 6-Hydroxydopamine lesions of the ventral tegmentum abolish D-amphetamine and morphine analgesia in the formalin test but not in the tail flick test. Brain Res 519:144–149CrossRefPubMed

Morris CJ (2003) Carrageenan-induced paw edema in the rat and mouse. Methods Mol Biol 225:115–121. doi:10.1385/1-59259-374-7:115 PubMed

Namburi P, Beyeler A, Yorozu S et al (2015) A circuit mechanism for differentiating positive and negative associations. Nature 520:675–678. doi:10.1038/nature14366 CrossRefPubMedPubMedCentral

Navratilova E, Xie JY, Okun A et al (2012) Pain relief produces negative reinforcement through activation of mesolimbic reward-valuation circuitry. Proc Natl Acad Sci USA 109:20709–20713. doi:10.1073/pnas.1214605109 CrossRefPubMedPubMedCentral

Neugebauer V, Li W, Bird GC, Han JS (2004) The amygdala and persistent pain. Neuroscientist 10:221–234. doi:10.1177/1073858403261077 CrossRefPubMed

Oliveras JL, Besson JM, Guilbaud G, Liebeskind JC (1974) Behavioral and electrophysiological evidence of pain inhibition from midbrain stimulation in the cat. Exp Brain Res 20:32–44CrossRefPubMed

Oliveras JL, Redjemi F, Guilbaud G, Besson JM (1975) Analgesia induced by electrical stimulation of the inferior centralis nucleus of the raphe in the cat. Pain 1:139–145CrossRefPubMed

Paxinos G, Waston C (1998) The rat brain in stereotaxic coordinates, 4th edn. Academic Press, San Diego

Peng YB, Lin Q, Willis WD (1996a) The role of 5-HT3 receptors in periaqueductal gray-induced inhibition of nociceptive dorsal horn neurons in rats. J Pharmacol Exp Ther 276:116–124PubMed

Peng YB, Lin Q, Willis WD (1996b) Involvement of alpha-2 adrenoceptors in the periaqueductal gray-induced inhibition of dorsal horn cell activity in rats. J Pharmacol Exp Ther 278:125–135PubMed

Peng YB, Lin Q, Willis WD (1996c) Effects of GABA and glycine receptor antagonists on the activity and PAG-induced inhibition of rat dorsal horn neurons. Brain Res 736:189–201CrossRefPubMed

Peng YB, Lin Q, Willis WD (1997) Involvement of protein kinase C in responses of rat dorsal horn neurons to mechanical stimuli and periaqueductal gray descending inhibition. Exp Brain Res 114:561–570CrossRefPubMed

Rainov N, Heidecke V (2006) Motor cortex stimulation for neuropathic facial pain. Neurol Res 21:E6

Rasche D, Rinaldi PC, Young RF, Tronnier VM (2006) Deep brain stimulation for the treatment of various chronic pain syndromes. Neurosurg Focus 21:E8. doi:10.3171/foc.2006.21.6.10 PubMed

Reynolds DV (1969) Surgery in the rat during electrical analgesia induced by focal brain stimulation. Science 164:444–445CrossRefPubMed

Richardson DE, Akil H (1977a) Pain reduction by electrical brain stimulation in man. Part 2: chronic self-administration in the periventricular gray matter. J Neurosurg 47:184–194. doi:10.3171/jns.1977.47.2.0184 CrossRefPubMed

Richardson DE, Akil H (1977b) Pain reduction by electrical brain stimulation in man. Part 1: acute administration in periaqueductal and periventricular sites. J Neurosurg 47:178–183CrossRefPubMed

Saadé NE, Atweh SF, Bahuth NB, Jabbur SJ (1997) Augmentation of nociceptive reflexes and chronic deafferentation pain by chemical lesions of either dopaminergic terminals or midbrain dopaminergic neurons. Brain Res 751:1–12CrossRefPubMed

Schifirnet E, Bowen SE, Borszcz GS (2014) Separating analgesia from reward within the ventral tegmental area. Neuroscience 263:72–87. doi:10.1016/j.neuroscience.2014.01.009 CrossRefPubMedPubMedCentral

Schultz W (1997) A neural substrate of prediction and reward. Science 275:1593–1599. doi:10.1126/science.275.5306.1593 CrossRefPubMed

Seijo F, Saiz A, Lozano B et al (2011) Neuromodulation of the posterolateral hypothalamus for the treatment of chronic refractory cluster headache: experience in five patients with a modified anatomical target. Cephalalgia 31:1634–1641. doi:10.1177/0333102411430264 CrossRefPubMed

Senapati AK, Huntington PJ, LaGraize SC et al (2005a) Electrical stimulation of the primary somatosensory cortex inhibits spinal dorsal horn neuron activity. Brain Res 1057:134–140. doi:10.1016/j.brainres.2005.07.044 CrossRefPubMed

Senapati AK, Huntington PJ, Peng YB (2005b) Spinal dorsal horn neuron response to mechanical stimuli is decreased by electrical stimulation of the primary motor cortex. Brain Res 1036:173–179. doi:10.1016/j.brainres.2004.12.043 CrossRefPubMed

Senapati AK, Lagraize SC, Huntington PJ et al (2005c) Electrical Stimulation of the Anterior Cingulate Cortex Reduces Responses of Rat Dorsal Horn Neurons to Mechanical Stimuli. 94:845–851. doi:10.1152/jn.00040.2005

Shipley MT, Ennis M, Rizvi TA, Behbehani MM (1991) The midbrain periaqueductal gray matter. Springer, Boston

Sibi JE, Zuo C, Wang Y et al (2012) Stimulation of ventral tegmental area increases mechanical pain threshold and thermal pain latency in rats. In: Annual meeting of the Society for Neuroscience, New Orleans

Sotres-Bayón F, Torres-López E, López-Avila A et al (2001) Lesion and electrical stimulation of the ventral tegmental area modify persistent nociceptive behavior in the rat. Brain Res 898:342–349CrossRefPubMed

Spooner J, Yu H, Kao C et al (2007) Neuromodulation of the cingulum for neuropathic pain after spinal cord injury. Case report. J Neurosurg 107:169–172. doi:10.3171/JNS-07/07/0169 CrossRefPubMed

Swanson LW (1982) The projections of the ventral tegmental area and adjacent regions: a combined fluorescent retrograde tracer and immunofluorescence study in the rat. Brain Res Bull 9:321–353CrossRefPubMed

Takeda R, Ikeda T, Tsuda F et al (2005) Unilateral lesions of mesostriatal dopaminergic pathway alters the withdrawal response of the rat hindpaw to mechanical stimulation. Neurosci Res 52:31–36. doi:10.1016/j.neures.2005.01.005 CrossRefPubMed

Taylor BK, Joshi C, Uppal H (2003) Stimulation of dopamine D2 receptors in the nucleus accumbens inhibits inflammatory pain. Brain Res 987:135–143CrossRefPubMed

Tsubokawa T, Katayama Y, Yamamoto T et al (1991) Chronic motor cortex stimulation for the treatment of central pain. Acta Neurochir Suppl (Wien) 52:137–139CrossRef

Unruh AM (1996) Gender variations in clinical pain experience. Pain 65:123–167CrossRefPubMed

Waters AJ, Lumb BM (1997) Inhibitory effects evoked from both the lateral and ventrolateral periaqueductal grey are selective for the nociceptive responses of rat dorsal horn neurones. Brain Res 752:239–249. doi:10.1016/S0006-8993(96)01462-X CrossRefPubMed

Whalley K (2015) Neural circuits: pain or pleasure? Nat Rev Neurosci 16:316. doi:10.1038/nrn3975 CrossRefPubMed

Wiech K, Kalisch R, Weiskopf N et al (2006) Anterolateral prefrontal cortex mediates the analgesic effect of expected and perceived control over pain. J Neurosci 26:11501–11509. doi:10.1523/JNEUROSCI.2568-06.2006 CrossRefPubMedPubMedCentral

Wiesenfeldhallin Z (2005) Sex differences in pain perception. Gend Med 2:137–145. doi:10.1016/S1550-8579(05)80042-7 CrossRef

Winter CA, Risley EA, Nuss GW (1962) Carrageenin-induced edema in hind paw of the rat as an assay for antiinflammatory drugs. Proc Soc Exp Biol Med 111:544–547CrossRefPubMed

Wood PB (2006) Mesolimbic dopaminergic mechanisms and pain control. Pain 120:230–234. doi:10.1016/j.pain.2005.12.014 CrossRefPubMed

Wood PB (2008) Role of central dopamine in pain and analgesia. Expert Rev Neurother 8:781–797. doi:10.1586/14737175.8.5.781 CrossRefPubMed

Wood PB, Patterson JC, Sunderland JJ et al (2007) Reduced presynaptic dopamine activity in fibromyalgia syndrome demonstrated with positron emission tomography: a pilot study. J Pain 8:51–58. doi:10.1016/j.jpain.2006.05.014 CrossRefPubMed

Wood PB, Glabus MF, Simpson R, Patterson JC (2009) Changes in gray matter density in fibromyalgia: correlation with dopamine metabolism. J Pain 10:609–618. doi:10.1016/j.jpain.2008.12.008 CrossRefPubMed

Young RF, Kroening R, Fulton W et al (1985) Electrical stimulation of the brain in treatment of chronic pain. J Neurosurg 62:389–396CrossRefPubMed

Zimmermann M (1983) Ethical guidelines for investigations of experimental pain in conscious animals. Pain 16:109–110CrossRefPubMed

Zuo C, Yang X, Wang Y et al (2012) A digital wireless system for closed-loop inhibition of nociceptive signals. J Neural Eng 9:056010. doi:10.1088/1741-2560/9/5/056010 CrossRefPubMed

Titel: Stimulation of the ventral tegmental area increased nociceptive thresholds and decreased spinal dorsal horn neuronal activity in rat
verfasst von: Ai-Ling Li
Jiny E. Sibi
Xiaofei Yang
Jung-Chih Chiao
Yuan Bo Peng
Publikationsdatum: 01.06.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Experimental Brain Research / Ausgabe 6/2016
Print ISSN: 0014-4819
Elektronische ISSN: 1432-1106
DOI: https://doi.org/10.1007/s00221-016-4558-z

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