Kappa opioid signaling in the central nucleus of the amygdala promotes disinhibition and aversiveness of chronic neuropathic pain

Pain - Tập 160 Số 4 - Trang 824-832 - 2019
Edita Navratilova1,2, Guangchen Ji3,2, Caroline E. Phelps1,2, Chenchen Qu1,2, Matthew Hein3,2, Vadim Yakhnitsa3,2, Volker Neugebauer3,2, Frank Porreca1
1Department of Pharmacology, Arizona Health Sciences Center, University of Arizona, Tucson, AZ, United States
2Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
3Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX, United States

Tóm tắt

Abstract Chronic pain is associated with neuroplastic changes in the amygdala that may promote hyper-responsiveness to mechanical and thermal stimuli (allodynia and hyperalgesia) and/or enhance emotional and affective consequences of pain. Stress promotes dynorphin-mediated signaling at the kappa opioid receptor (KOR) in the amygdala and mechanical hypersensitivity in rodent models of functional pain. Here, we tested the hypothesis that KOR circuits in the central nucleus of the amygdala (CeA) undergo neuroplasticity in chronic neuropathic pain resulting in increased sensory and affective pain responses. After spinal nerve ligation (SNL) injury in rats, pretreatment with a long-acting KOR antagonist, nor-binaltorphimine (nor-BNI), subcutaneously or through microinjection into the right CeA, prevented conditioned place preference (CPP) to intravenous gabapentin, suggesting that nor-BNI eliminated the aversiveness of ongoing pain. By contrast, systemic or intra-CeA administration of nor-BNI had no effect on tactile allodynia in SNL animals. Using whole-cell patch-clamp electrophysiology, we found that nor-BNI decreased synaptically evoked spiking of CeA neurons in brain slices from SNL but not sham rats. This effect was mediated through increased inhibitory postsynaptic currents, suggesting tonic disinhibition of CeA output neurons due to increased KOR activity as a possible mechanism promoting ongoing aversive aspects of neuropathic pain. Interestingly, this mechanism is not involved in SNL-induced mechanical allodynia. Kappa opioid receptor antagonists may therefore represent novel therapies for neuropathic pain by targeting aversive aspects of ongoing pain while preserving protective functions of acute pain.

Từ khóa


Tài liệu tham khảo

Arora, 2018, Psychosocial stress delays recovery of postoperative pain following incisional surgery in the rat, Neuroscience, 382, 35, 10.1016/j.neuroscience.2018.04.014

Baliki, 2015, Nociception, pain, negative moods, and behavior selection, Neuron, 87, 474, 10.1016/j.neuron.2015.06.005

Bannister, 2017, Multiple sites and actions of gabapentin-induced relief of ongoing experimental neuropathic pain, PAIN, 158, 2386, 10.1097/j.pain.0000000000001040

Beckerman, 2013, Corticotropin-releasing factor in the mouse central nucleus of the amygdala: ultrastructural distribution in NMDA-NR1 receptor subunit expressing neurons as well as projection neurons to the bed nucleus of the stria terminalis, Exp Neurol, 239, 120, 10.1016/j.expneurol.2012.10.009

Borsook, 2012, Understanding migraine through the lens of maladaptive stress responses: a model disease of allostatic load, Neuron, 73, 219, 10.1016/j.neuron.2012.01.001

Bourke, 2015, The common link between functional somatic syndromes may be central sensitisation, J Psychosom Res, 78, 228, 10.1016/j.jpsychores.2015.01.003

Bruchas, 2010, The dynorphin/kappa opioid system as a modulator of stress-induced and pro-addictive behaviors, Brain Res, 1314, 44, 10.1016/j.brainres.2009.08.062

Cai, 2014, Central amygdala PKC-delta(+) neurons mediate the influence of multiple anorexigenic signals, Nat Neurosci, 17, 1240, 10.1038/nn.3767

Carrasquillo, 2008, Hemispheric lateralization of a molecular signal for pain modulation in the amygdala, Mol Pain, 4, 24, 10.1186/1744-8069-4-24

Chen, 2017, Altered functional connectivity of amygdala underlying the neuromechanism of migraine pathogenesis, J Headache Pain, 18, 7, 10.1186/s10194-017-0722-5

Ciocchi, 2010, Encoding of conditioned fear in central amygdala inhibitory circuits, Nature, 468, 277, 10.1038/nature09559

Fendt, 1997, Corticotropin-releasing factor in the caudal pontine reticular nucleus mediates the expression of fear-potentiated startle in the rat, Eur J Neurosci, 9, 299, 10.1111/j.1460-9568.1997.tb01400.x

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

Gauriau, 2002, Pain pathways and parabrachial circuits in the rat, Exp Physiol, 87, 251, 10.1113/eph8702357

Harrigan, 1994, Corticotropin releasing factor neurons are innervated by calcitonin gene-related peptide terminals in the rat central amygdaloid nucleus, Brain Res Bull, 33, 529, 10.1016/0361-9230(94)90079-5

Haubensak, 2010, Genetic dissection of an amygdala microcircuit that gates conditioned fear, Nature, 468, 270, 10.1038/nature09553

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

Iliopoulos, 2015, Trigger factors in primary headaches subtypes: a cross-sectional study from a tertiary centre in Greece, BMC Res Notes, 8, 393, 10.1186/s13104-015-1390-7

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

Ji, 2009, Hemispheric lateralization of pain processing by amygdala neurons, J Neurophysiol, 102, 2253, 10.1152/jn.00166.2009

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

Jiang, 2016, Perturbed connectivity of the amygdala and its subregions with the central executive and default mode networks in chronic pain, PAIN, 157, 1970, 10.1097/j.pain.0000000000000606

Jongen-Relo, 1998, Evidence for a GABAergic projection from the central nucleus of the amygdala to the brainstem of the macaque monkey: a combined retrograde tracing and in situ hybridization study, Eur J Neurosci, 10, 2924, 10.1111/j.1460-9568.1998.00299.x

Kim, 1992, An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat, PAIN, 50, 355, 10.1016/0304-3959(92)90041-9

King, 2009, Unmasking the tonic-aversive state in neuropathic pain, Nat Neurosci, 12, 1364, 10.1038/nn.2407

Kiritoshi, 2016, Rescue of impaired mGluR5-driven endocannabinoid signaling restores prefrontal cortical output to inhibit pain in arthritic rats, J Neurosci, 36, 837, 10.1523/JNEUROSCI.4047-15.2016

Knoll, 2010, Dynorphin, stress, and depression, Brain Res, 1314, 56, 10.1016/j.brainres.2009.09.074

Kozono, 2018, Post-marketing surveillance study of the safety and efficacy of nalfurafine hydrochloride (Remitch((R)) capsules 2.5 mug) in 3,762 hemodialysis patients with intractable pruritus, Int J Nephrol Renovasc Dis, 11, 9, 10.2147/IJNRD.S145720

Kuo, 2005, Comparison of anterior cingulate and primary somatosensory neuronal responses to noxious laser-heat stimuli in conscious, behaving rats, J Neurophysiol, 94, 1825, 10.1152/jn.00294.2005

Lazenka, 2018, Dissociable effects of the kappa opioid receptor agonist nalfurafine on pain/itch-stimulated and pain/itch-depressed behaviors in male rats, Psychopharmacology (Berl), 235, 203, 10.1007/s00213-017-4758-7

Maixner, 2016, Overlapping chronic pain conditions: implications for diagnosis and classification, J Pain, 17, T93, 10.1016/j.jpain.2016.06.002

Malan, 2000, Extraterritorial neuropathic pain correlates with multisegmental elevation of spinal dynorphin in nerve-injured rats, PAIN, 86, 185, 10.1016/S0304-3959(00)00243-8

Maleki, 2012, Migraine: maladaptive brain responses to stress, Headache, 52, 102, 10.1111/j.1526-4610.2012.02241.x

McCall, 2015, CRH engagement of the locus coeruleus noradrenergic system mediates stress-induced anxiety, Neuron, 87, 605, 10.1016/j.neuron.2015.07.002

Mitchell, 2014, Intra-VTA deltorphin, but not DPDPE, induces place preference in ethanol-drinking rats: distinct DOR-1 and DOR-2 mechanisms control ethanol consumption and reward, Alcohol Clin Exp Res, 38, 195, 10.1111/acer.12246

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

Nation, 2018, Lateralized kappa opioid receptor signaling from the amygdala central nucleus promotes stress-induced functional pain, PAIN, 159, 919, 10.1097/j.pain.0000000000001167

Navratilova, 2013, Evaluation of reward from pain relief, Ann N Y Acad Sci, 1282, 1, 10.1111/nyas.12095

Navratilova, 2015, Endogenous opioid activity in the anterior cingulate cortex is required for relief of pain, J Neurosci, 35, 7264, 10.1523/JNEUROSCI.3862-14.2015

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

Neugebauer, 2009, Forebrain pain mechanisms, Brain Res Rev, 60, 226, 10.1016/j.brainresrev.2008.12.014

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

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

Pande, 1996, Analgesic efficacy of the kappa-receptor agonist, enadoline, in dental surgery pain, Clin Neuropharmacol, 19, 92, 10.1097/00002826-199619010-00009

Pande, 1996, Analgesic efficacy of enadoline versus placebo or morphine in postsurgical pain, Clin Neuropharmacol, 19, 451, 10.1097/00002826-199619050-00009

Phillips, 2011, Central pain mechanisms in chronic pain states—maybe it is all in their head, Best Pract Res Clin Rheumatol, 25, 141, 10.1016/j.berh.2011.02.005

Pomrenze, 2015, A transgenic rat for investigating the anatomy and function of corticotrophin releasing factor circuits, Front Neurosci, 9, 487, 10.3389/fnins.2015.00487

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

Ren, 2010, Pain-related increase of excitatory transmission and decrease of inhibitory transmission in the central nucleus of the amygdala are mediated by mGluR1, Mol Pain, 6, 93, 10.1186/1744-8069-6-93

Reyes, 2011, Amygdalar peptidergic circuits regulating noradrenergic locus coeruleus neurons: linking limbic and arousal centers, Exp Neurol, 230, 96, 10.1016/j.expneurol.2011.04.001

Sarhan, 2005, Branching patterns of parabrachial neurons projecting to the central extended amgydala: single axonal reconstructions, J Comp Neurol, 491, 418, 10.1002/cne.20697

Schiess, 1999, Characterization of the electrophysiological and morphological properties of rat central amygdala neurons in vitro, J Neurosci Res, 58, 663, 10.1002/(SICI)1097-4547(19991201)58:5<663::AID-JNR7>3.0.CO;2-A

Schwaber, 1988, Neurons containing calcitonin gene-related peptide in the parabrachial nucleus project to the central nucleus of the amygdala, J Comp Neurol, 270, 416, 10.1002/cne.902700310

Sibille, 2017, Accelerated aging in adults with knee osteoarthritis pain: consideration for frequency, intensity, time, and total pain sites, Pain Rep, 2, e591, 10.1097/PR9.0000000000000591

Simons, 2014, The human amygdala and pain: evidence from neuroimaging, Hum Brain Mapp, 35, 527, 10.1002/hbm.22199

Sluka, 2016, Neurobiology of fibromyalgia and chronic widespread pain, Neuroscience, 338, 114, 10.1016/j.neuroscience.2016.06.006

Sun, 1993, Intrinsic GABAergic neurons in the rat central extended amygdala, J Comp Neurol, 330, 381, 10.1002/cne.903300308

Taylor, 2016, Kappa opioids, salvinorin A and major depressive disorder, Curr Neuropharmacol, 14, 165, 10.2174/1570159X13666150727220944

Tepper, 2012, Medication-overuse headache, Continuum (Minneap Minn), 18, 807

Vachon-Presseau, 2016, Corticolimbic anatomical characteristics predetermine risk for chronic pain, Brain, 139, 1958, 10.1093/brain/aww100

Wang, 2001, Pronociceptive actions of dynorphin maintain chronic neuropathic pain, J Neurosci, 21, 1779, 10.1523/JNEUROSCI.21-05-01779.2001

Watabe, 2013, Synaptic potentiation in the nociceptive amygdala following fear learning in mice, Mol Brain, 6, 11, 10.1186/1756-6606-6-11

Woolf, 2007, Central sensitization: uncovering the relation between pain and plasticity, Anesthesiology, 106, 864, 10.1097/01.anes.0000264769.87038.55

Xie, 2017, Kappa opioid receptor antagonists: a possible new class of therapeutics for migraine prevention, Cephalalgia, 37, 780, 10.1177/0333102417702120

Thông tin
Thông tin xuất bản

Pain

Tập 160 Số 4

824-832

Thông tin tác giả