Contribution of Corticotropin-Releasing Factor Receptor 1 (CRF1) to Serotonin Receptor 5-HT2CR Function in Amygdala Neurons in a Neuropathic Pain Model

International Journal of Molecular Sciences - Tập 20 Số 18 - Trang 4380
Guangchen Ji1,2, Volker Neugebauer3,4,5
1Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, Lubbock, TX 79424, USA.
2Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79424, USA.
3Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, Lubbock, TX 79424, USA. [email protected].
4Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79424, USA. [email protected].
5Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX 79424, USA. [email protected].

Tóm tắt

The amygdala plays a key role in emotional-affective aspects of pain and in pain modulation. The central nucleus (CeA) serves major amygdala output functions related to emotional-affective behaviors and pain modulation. Our previous studies implicated the corticotropin-releasing factor (CRF) system in amygdala plasticity and pain behaviors in an arthritis model. We also showed that serotonin (5-HT) receptor subtype 5-HT2CR in the basolateral amygdala (BLA) contributes to increased CeA output and neuropathic pain-like behaviors. Here, we tested the novel hypothesis that 5-HT2CR in the BLA drives CRF1 receptor activation to increase CeA neuronal activity in neuropathic pain. Extracellular single-unit recordings of CeA neurons in anesthetized adult male rats detected increased activity in neuropathic rats (spinal nerve ligation model) compared to sham controls. Increased CeA activity was blocked by local knockdown or pharmacological blockade of 5-HT2CR in the BLA, using stereotaxic administration of 5-HT2CR short hairpin RNA (shRNA) viral vector or a 5-HT2CR antagonist (SB242084), respectively. Stereotaxic administration of a CRF1 receptor antagonist (NBI27914) into the BLA also decreased CeA activity in neuropathic rats and blocked the facilitatory effects of a 5-HT2CR agonist (WAY161503) administered stereotaxically into the BLA. Conversely, local (BLA) knockdown of 5-HT2CR eliminated the inhibitory effect of NBI27914 and the facilitatory effect of WAY161503 in neuropathic rats. The data suggest that 5-HT2CR activation in the BLA contributes to neuropathic pain-related amygdala (CeA) activity by engaging CRF1 receptor signaling.

Từ khóa


Tài liệu tham khảo

Heinricher, 2009, Descending control of nociception: Specificity, recruitment and plasticity, Brain Res. Rev., 60, 214, 10.1016/j.brainresrev.2008.12.009

Ossipov, 2010, Central modulation of pain, J. Clin. Investig., 120, 3779, 10.1172/JCI43766

Sommer, 2006, Is serotonin hyperalgesic or analgesic?, Curr. Pain Headache Rep., 10, 101, 10.1007/s11916-006-0020-4

Suzuki, 2004, Bad news from the brain: Descending 5-HT pathways that control spinal pain processing, Trends Pharmacol. Sci., 25, 613, 10.1016/j.tips.2004.10.002

Bockaert, 2006, Neuronal 5-HT metabotropic receptors: Fine-tuning of their structure, signaling, and roles in synaptic modulation, Cell Tissue Res., 326, 553, 10.1007/s00441-006-0286-1

Hannon, 2008, Molecular biology of 5-HT receptors, Serotonin Sleep Mol. Funct. Clin. Asp., 195, 155, 10.1007/978-3-7643-8561-3_6

Marin, 2008, Signaling at G-protein-coupled serotonin receptors: Recent advances and future research directions, Trends Pharmacol. Sci., 29, 454, 10.1016/j.tips.2008.06.007

Dworkin, 2010, Recommendations for the Pharmacological Management of Neuropathic Pain: An Overview and Literature Update, Mayo Clin. Proc., 85, S3, 10.4065/mcp.2009.0649

Finnerup, 2015, Pharmacotherapy for Neuropathic Pain in Adults: A Systematic Review and Meta-Analysis, J. Vasc. Surg., 62, 1091, 10.1016/j.jvs.2015.08.010

Lee, 2010, A review of SSRIs and SNRIs in neuropathic pain, Expert Opin. Pharmacother., 11, 2813, 10.1517/14656566.2010.507192

Napoletano, 2014, Sumatriptan in clinical practice: Effectiveness in migraine and the problem of psychiatric comorbidity, Expert Opin. Pharmacother., 15, 303, 10.1517/14656566.2014.858120

Negro, 2018, Serotonin receptor agonists in the acute treatment of migraine: A review on their therapeutic potential, J. Pain Res., 11, 515, 10.2147/JPR.S132833

Jensen, 2010, Therapeutic Potential of 5-HT2C Receptor Ligands, Sci. World J., 10, 1870, 10.1100/tsw.2010.180

Christiansen, 2011, A candidate gene study of serotonergic pathway genes and pain relief during treatment with escitalopram in patients with neuropathic pain shows significant association to serotonin receptor2C (HTR2C), Eur. J. Clin. Pharmacol., 67, 1131, 10.1007/s00228-011-1056-x

Vicente, 2014, Involvement of 5-HT2C and 5-HT1A receptors of the basolateral nucleus of the amygdala in the anxiolytic effect of chronic antidepressant treatment, Neuropharmacology, 79, 127, 10.1016/j.neuropharm.2013.11.007

Phelps, 2005, Contributions of the Amygdala to Emotion Processing: From Animal Models to Human Behavior, Neuron, 48, 175, 10.1016/j.neuron.2005.09.025

Clemett, 2000, Immunohistochemical localisation of the 5-HT2C receptor protein in the rat CNS, Neuropharmacology, 39, 123, 10.1016/S0028-3908(99)00086-6

Pompeiano, 1994, Distribution of the serotonin 5-HT2 receptor family mRNAs: Comparison between 5-HT2A and 5-HT2C receptors, Mol. Brain Res., 23, 163, 10.1016/0169-328X(94)90223-2

Bocchio, 2016, Serotonin, Amygdala and Fear: Assembling the Puzzle, Front. Neural Circuits, 10, 24, 10.3389/fncir.2016.00024

Ma, 1991, Serotonergic projections from the nucleus raphe dorsalis to the amygdala in the rat, Neurosci. Lett., 134, 21, 10.1016/0304-3940(91)90499-J

Christianson, 2010, 5-hydroxytryptamine 2C receptors in the basolateral amygdala are involved in the expression of anxiety after uncontrollable traumatic stress, Biol. Psychiatry, 67, 339, 10.1016/j.biopsych.2009.09.011

Funada, 2001, Differential effects of psychological stress on activation of the 5-hydroxytryptamine- and dopamine-containing neurons in the brain of freely moving rats, Brain Res., 901, 247, 10.1016/S0006-8993(01)02160-6

Macedo, 2005, Increases in extracellular levels of 5-HT and dopamine in the basolateral, but not in the central, nucleus of amygdala induced by aversive stimulation of the inferior colliculus, Eur. J. Neurosci., 21, 1131, 10.1111/j.1460-9568.2005.03939.x

Kimura, 2009, Overexpression of 5-HT2C receptors in forebrain leads to elevated anxiety and hypoactivity, Eur. J. Neurosci., 30, 299, 10.1111/j.1460-9568.2009.06831.x

Li, 2012, Anxiolytic effects of 5-HT1A receptors and anxiogenic effects of 5-HT2C receptors in the amygdala of mice, Neuropharmacology, 62, 474, 10.1016/j.neuropharm.2011.09.002

Heisler, 2007, Serotonin 5-HT(2C) receptors regulate anxiety-like behavior, Genes Brain Behav., 6, 491, 10.1111/j.1601-183X.2007.00316.x

Campbell, 2003, Serotonin 2C receptors within the basolateral amygdala induce acute fear-like responses in an open-field environment, Brain Res., 993, 1, 10.1016/S0006-8993(03)03384-5

Vicente, 2012, Serotonin-2C receptors in the basolateral nucleus of the amygdala mediate the anxiogenic effect of acute imipramine and fluoxetine administration, Int. J. Neuropsychopharmacol., 15, 389, 10.1017/S1461145711000873

Pinheiro, 2005, Behavioral effects of systemically administered MK-212 are prevented by ritanserin microinfusion into the basolateral amygdala of rats exposed to the elevated plus-maze, Psychopharmacology, 182, 345, 10.1007/s00213-005-0108-2

Neugebauer, 2015, Amygdala pain mechanisms, Handb. Exp. Pharmacol., 227, 261, 10.1007/978-3-662-46450-2_13

Neugebauer, 2004, The amygdala and persistent pain, Neuroscientist, 10, 221, 10.1177/1073858403261077

Thompson, 2017, Amygdala Plasticity and Pain, Pain Res. Manag., 2017, 8296501, 10.1155/2017/8296501

Adedoyin, 2010, Endogenous N-acetylaspartylglutamate (NAAG) inhibits synaptic plasticity/transmission in the amygdala in a mouse inflammatory pain model, Mol. Pain, 6, 60, 10.1186/1744-8069-6-60

Bird, 2005, Protein kinase A-dependent enhanced NMDA receptor function in pain-related synaptic plasticity in rat amygdala neurones, J. Physiol., 564, 907, 10.1113/jphysiol.2005.084780

Cheng, 2011, Role of Extracellular Signal-Regulated Kinase in Synaptic Transmission and Plasticity of a Nociceptive Input on Capsular Central Amygdaloid Neurons in Normal and Acid-Induced Muscle Pain Mice, J. Neurosci., 31, 2258, 10.1523/JNEUROSCI.5564-10.2011

Fu, 2008, Differential mechanisms of CRF1 and CRF2 receptor functions in the amygdala in pain-related synaptic facilitation and behavior, J. Neurosci., 28, 3861, 10.1523/JNEUROSCI.0227-08.2008

Han, 2005, Critical Role of Calcitonin Gene-Related Peptide 1 Receptors in the Amygdala in Synaptic Plasticity and Pain Behavior, J. Neurosci., 25, 10717, 10.1523/JNEUROSCI.4112-05.2005

Ji, 2015, Reactive oxygen species mediate visceral pain–related amygdala plasticity and behaviors, Pain, 156, 825, 10.1097/j.pain.0000000000000120

Neugebauer, 2003, Synaptic Plasticity in the Amygdala in a Model of Arthritic Pain: Differential Roles of Metabotropic Glutamate Receptors 1 and 5, J. Neurosci., 23, 52, 10.1523/JNEUROSCI.23-01-00052.2003

Ren, 2013, Neuropeptide S: A novel regulator of pain-related amygdala plasticity and behaviors, J. Neurophysiol., 110, 1765, 10.1152/jn.00874.2012

Shinohara, 2017, Essential role of endogenous calcitonin gene-related peptide in pain-associated plasticity in the central amygdala, Eur. J. Neurosci., 46, 2149, 10.1111/ejn.13662

Sugimura, 2016, Synaptic and network consequences of monosynaptic nociceptive inputs of parabrachial nucleus origin in the central amygdala, J. Neurophysiol., 115, 2721, 10.1152/jn.00946.2015

Silva, 2008, Neuropathic pain is associated with depressive behaviour and induces neuroplasticity in the amygdala of the rat, Exp. Neurol., 213, 48, 10.1016/j.expneurol.2008.04.043

Ikeda, 2007, NMDA receptor-independent synaptic plasticity in the central amygdala in the rat model of neuropathic pain, Pain, 127, 161, 10.1016/j.pain.2006.09.003

Ji, 2017, 5-HT2C Receptor Knockdown in the Amygdala Inhibits Neuropathic-Pain-Related Plasticity and Behaviors, J. Neurosci., 37, 1378, 10.1523/JNEUROSCI.2468-16.2016

Nakao, 2012, Role of capsaicin-sensitive C-fiber afferents in neuropathic pain-induced synaptic potentiation in the nociceptive amygdala, Mol. Pain, 8, 51, 10.1186/1744-8069-8-51

Dickenson, 2012, Asymmetric time-dependent activation of right central amygdala neurones in rats with peripheral neuropathy and pregabalin modulation, Eur. J. Neurosci., 36, 3204, 10.1111/j.1460-9568.2012.08235.x

Ji, 2007, Differential Effects of CRF1 and CRF2 Receptor Antagonists on Pain-Related Sensitization of Neurons in the Central Nucleus of the Amygdala, J. Neurophysiol., 97, 3893, 10.1152/jn.00135.2007

Ji, 2009, Hemispheric Lateralization of Pain Processing by Amygdala Neurons, J. Neurophysiol., 102, 2253, 10.1152/jn.00166.2009

Ji, 2010, Reactive Oxygen Species Are Involved in Group I mGluR-Mediated Facilitation of Nociceptive Processing in Amygdala Neurons, J. Neurophysiol., 104, 218, 10.1152/jn.00223.2010

Li, 2004, Block of NMDA and non-NMDA receptor activation results in reduced background and evoked activity of central amygdala neurons in a model of arthritic pain, Pain, 110, 112, 10.1016/j.pain.2004.03.015

Li, 2004, Differential Roles of mGluR1 and mGluR5 in Brief and Prolonged Nociceptive Processing in Central Amygdala Neurons, J. Neurophysiol., 91, 13, 10.1152/jn.00485.2003

Li, 2006, Differential Changes of Group II and Group III mGluR Function in Central Amygdala Neurons in a Model of Arthritic Pain, J. Neurophysiol., 96, 1803, 10.1152/jn.00495.2006

Medina, 2014, Nasal Application of Neuropeptide S Inhibits Arthritis Pain-Related Behaviors through an Action in the Amygdala, Mol. Pain, 10, 32, 10.1186/1744-8069-10-32

Neugebauer, 2003, Differential Sensitization of Amygdala Neurons to Afferent Inputs in a Model of Arthritic Pain, J. Neurophysiol., 89, 716, 10.1152/jn.00799.2002

Ji, 2010, Cognitive impairment in pain through amygdala-driven prefrontal cortical deactivation, J. Neurosci., 30, 5451, 10.1523/JNEUROSCI.0225-10.2010

Chen, 2003, Serotonin type II receptor activation facilitates synaptic plasticity via n-methyl-d-aspartate-mediated mechanism in the rat basolateral amygdala, Neuroscience, 119, 53, 10.1016/S0306-4522(03)00076-9

Sengupta, 2017, Control of Amygdala Circuits by 5-HT Neurons via 5-HT and Glutamate Cotransmission, J. Neurosci., 37, 1785, 10.1523/JNEUROSCI.2238-16.2016

Guo, 2017, Serotonin gating of cortical and thalamic glutamate inputs onto principal neurons of the basolateral amygdala, Neuropharmacology, 126, 224, 10.1016/j.neuropharm.2017.09.013

Rainnie, 1999, Serotonergic Modulation of Neurotransmission in the Rat Basolateral Amygdala, J. Neurophysiol., 82, 69, 10.1152/jn.1999.82.1.69

Neugebauer, 2013, 5-HT2CR blockade in the amygdala conveys analgesic efficacy to SSRIs in a rat model of arthritis pain, Mol. Pain, 9, 41

Neugebauer, 2002, Processing of Nociceptive Mechanical and Thermal Information in Central Amygdala Neurons with Knee-Joint Input, J. Neurophysiol., 87, 103, 10.1152/jn.00264.2001

Anastasio, 2015, Serotonin (5-HT) 5-HT2A Receptor (5-HT2AR):5-HT2CR Imbalance in Medial Prefrontal Cortex Associates with Motor Impulsivity, ACS Chem. Neurosci., 6, 1248, 10.1021/acschemneuro.5b00094

Anastasio, 2014, Functional status of the serotonin 5-HT2C receptor (5-HT2CR) drives interlocked phenotypes that precipitate relapse-like behaviors in cocaine dependence, Neuropsychopharmacology, 39, 370, 10.1038/npp.2013.199

Wold, E.A., Wild, C.T., Cunningham, K.A., and Zhou, J. (2019). Targeting the 5-HT2C Receptor in Biological Context and the Current State of 5-HT2C Receptor Ligand Development. Curr. Top. Med. Chem., 19.

Vicente, 2019, Role of 5-HT2C receptors of the dorsal hippocampus in the modulation of anxiety- and panic-related defensive responses in rats, Neuropharmacology, 148, 311, 10.1016/j.neuropharm.2019.01.026

Asan, 2005, The Corticotropin-Releasing Factor (CRF)-system and monoaminergic afferents in the central amygdala: Investigations in different mouse strains and comparison with the rat, Neuroscience, 131, 953, 10.1016/j.neuroscience.2004.11.040

Bale, 2004, CRF and CRF receptors: Role in stress responsivity and other behaviors, Annu. Rev. Pharmacol. Toxicol., 44, 525, 10.1146/annurev.pharmtox.44.101802.121410

Gray, 1993, Amygdaloid CRF Pathways: Role in Autonomic, Neuroendocrine, and Behavioral Responses to Stress, Ann. N. Y. Acad. Sci., 697, 53, 10.1111/j.1749-6632.1993.tb49922.x

Pomrenze, 2015, A Transgenic Rat for Investigating the Anatomy and Function of Corticotrophin Releasing Factor Circuits, Front. Mol. Neurosci., 9, 5626

Reul, 2002, Corticotropin-releasing factor receptors 1 and 2 in anxiety and depression, Curr. Opin. Pharmacol., 2, 23, 10.1016/S1471-4892(01)00117-5

Chen, 2000, Immunocytochemical distribution of corticotropin-releasing hormone receptor type-1 (CRF1)-like immunoreactivity in the mouse brain: Light microscopy analysis using an antibody directed against the C-terminus, J. Comp. Neurol., 420, 305, 10.1002/(SICI)1096-9861(20000508)420:3<305::AID-CNE3>3.0.CO;2-8

Johnson, 2006, Long-term expression of corticotropin-releasing factor (CRF) in the paraventricular nucleus of the hypothalamus in response to an acute colonic inflammation, Brain Res., 1071, 91, 10.1016/j.brainres.2005.11.071

Lariviere, 2000, The role of corticotropin-releasing factor in pain and analgesia, Pain, 84, 1, 10.1016/S0304-3959(99)00193-1

McNally, 2002, Role of corticotropin-releasing hormone in the amygdala and bed nucleus of the stria terminalis in the behavioral, pain modulatory, and endocrine consequences of opiate withdrawal, Neuroscience, 112, 605, 10.1016/S0306-4522(02)00105-7

Sinniger, 2004, c-fos and CRF receptor gene transcription in the brain of acetic acid-induced somato-visceral pain in rats, Pain, 110, 738, 10.1016/j.pain.2004.05.014

Xie, 2006, Limbic and HPA axis function in an animal model of chronic neuropathic pain, Physiol. Behav., 88, 67, 10.1016/j.physbeh.2006.03.012

Fernandez, 2016, Multiscale single-cell analysis reveals unique phenotypes of raphe 5-HT neurons projecting to the forebrain, Brain Struct. Funct., 221, 4007, 10.1007/s00429-015-1142-4

Muller, 2007, Serotonin-immunoreactive axon terminals innervate pyramidal cells and interneurons in the rat basolateral amygdala, J. Comp. Neurol., 505, 314, 10.1002/cne.21486

Parent, 1981, Organization of ascending serotonin systems in the adult rat brain. A radioautographic study after intraventricular administration of [3H]5-hydroxytryptamine, Neuroscience, 6, 115, 10.1016/0306-4522(81)90050-6

Pentkowski, 2014, Effects of the 5-HT2C receptor agonist CP809101 in the amygdala on reinstatement of cocaine-seeking behavior and anxiety-like behavior, Int. J. Neuropsychopharmacol., 17, 1751, 10.1017/S1461145714000856

Moya, P.R., Fox, M.A., Jensen, C.L., Laporte, J.L., French, H.T., Wendland, J.R., and Murphy, D.L. (2011). Altered 5-HT2C receptor agonist-induced responses and 5-HT2C receptor RNA editing in the amygdala of serotonin transporter knockout mice. BMC Pharmacol., 11.

Corder, 2019, An amygdalar neural ensemble that encodes the unpleasantness of pain, Science, 363, 276, 10.1126/science.aap8586

Veinante, 2013, The amygdala between sensation and affect: A role in pain, J. Mol. Psychiatry, 1, 9, 10.1186/2049-9256-1-9

Jasmin, 2003, Analgesia and hyperalgesia from GABA-mediated modulation of the cerebral cortex, Nature, 424, 316, 10.1038/nature01808

Heinricher, 2002, Microinjection of morphine into various amygdaloid nuclei differentially affects nociceptive responsiveness and RVM neuronal activity, Diabetes Nerv. Syst., 96, 153

Ji, 2013, Non-pain-related CRF1 activation in the amygdala facilitates synaptic transmission and pain responses, Mol. Pain, 9, 2, 10.1186/1744-8069-9-2

Ji, 2008, Pro- and Anti-Nociceptive Effects of Corticotropin-Releasing Factor (CRF) in Central Amygdala Neurons Are Mediated Through Different Receptors, J. Neurophysiol., 99, 1201, 10.1152/jn.01148.2007

Bennett, 2003, Models of Neuropathic Pain in the Rat, Curr. Protoc. Pharmacol., 9, 14

Ji, 2018, Fear extinction learning ability predicts neuropathic pain behaviors and amygdala activity in male rats, Mol. Pain, 14, 1744806918804441, 10.1177/1744806918804441

Ji, 2007, Pain-related anxiety-like behavior requires CRF1 receptors in the amygdala, Mol. Pain, 3, 13, 10.1186/1744-8069-3-13

Neugebauer, 2007, CRF1 receptors in the basolateral amygdala contribute to pain-related decision-making deficits, Soc. Neurosci. Abstr., 37, 723-3

Cunningham, 2011, Selective serotonin 5-HT2C receptor activation suppresses the reinforcing efficacy of cocaine and sucrose but differentially affects the incentive-salience value of cocaine- vs. sucrose-associated cues, Neuropharmacology, 61, 513, 10.1016/j.neuropharm.2011.04.034

Fletcher, 2009, Characterizing the effects of 5-HT2C receptor ligands on motor activity and feeding behaviour in 5-HT2C receptor knockout mice, Neuropharmacology, 57, 259, 10.1016/j.neuropharm.2009.05.011

Pentkowski, 2010, Stimulation of Medial Prefrontal Cortex Serotonin 2C (5-HT2C) Receptors Attenuates Cocaine-Seeking Behavior, Neuropsychopharmacology, 35, 2037, 10.1038/npp.2010.72