5-HT<sub>2C</sub>Receptor Knockdown in the Amygdala Inhibits Neuropathic-Pain-Related Plasticity and Behaviors

Ji, Guangchen; Zhang, Wei; Mahimainathan, Lenin; Narasimhan, Madhusudhanan; Kiritoshi, Takaki; Fan, Xueli; Wang, Jigong; Green, Thomas A.; Neugebauer, Volker

doi:10.1523/jneurosci.2468-16.2016

Cited by 71 publications

(96 citation statements)

References 94 publications

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“…Behavioral or electrophysiological studies were done four weeks after surgery when neuropathic pain-related behavioral and neuronal changes reach a stable plateau in this model. 26 In another set of control experiments, sensory and affective behaviors (mechanosensitivity, vocalizations, and open field test (OFT) performance) were measured two days before and two days after the fear conditioning/extinction trials to rule out any changes induced by the fear conditioning and extinction tests. The experimenter was blinded with regard to the FE phenotype (see fear conditioning and extinction) and neuropathic versus sham condition.…”

Section: Methodsmentioning

confidence: 99%

“…Paw withdrawal thresholds (expressed in g) were determined by the up-down method and the formula of Dixon as in our previous studies. 26 In some experiments, a plantar electronic von Frey anesthesiometer (IITC Life Science, Woodland Hills, CA) was used to measure mechanical thresholds. The tip was applied perpendicularly to the base of the third or fourth toe with increasing force until a flexion reflex was provoked, which was automatically recorded as the paw withdrawal threshold (in grams).…”

Section: Methodsmentioning

confidence: 99%

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Fear extinction learning ability predicts neuropathic pain behaviors and amygdala activity in male rats

Yakhnitsa

Kiritoshi

et al. 2018

Mol Pain

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BackgroundThe amygdala plays a key role in fear learning and extinction and has emerged as an important node of emotional-affective aspects of pain and pain modulation. Impaired fear extinction learning, which involves prefrontal cortical control of amygdala processing, has been linked to neuropsychiatric disorders. Here, we tested the hypothesis that fear extinction learning ability can predict the magnitude of neuropathic pain.ResultsWe correlated fear extinction learning in naive adult male rats with sensory and affective behavioral outcome measures (mechanical thresholds, vocalizations, and anxiety- and depression-like behaviors) before and after the induction of the spinal nerve ligation model of neuropathic pain compared to sham controls. Auditory fear conditioning, extinction learning, and extinction retention tests were conducted after baseline testing. All rats showed increased freezing responses after fear conditioning. During extinction training, the majority (75%) of rats showed a decline in freezing level to 50% in 5 min (fear extinction+), whereas 25% of the rats maintained a high freezing level (>50%, fear extinction−). Fear extinction− rats showed decreased open-arm preference in the elevated plus maze, reflecting anxiety-like behavior, but there were no significant differences in sensory thresholds, vocalizations, or depression-like behavior (forced swim test) between fear extinction+ and fear extinction− types. In the neuropathic pain model (four weeks after spinal nerve ligation), fear extinction− rats showed a greater increase in vocalizations and anxiety-like behavior than fear extinction+ rats. Fear extinction− rats, but not fear extinction+ rats, also developed depression-like behavior. Extracellular single unit recordings of amygdala (central nucleus) neurons in behaviorally tested rats (anesthetized with isoflurane) found greater increases in background activity, bursting, and evoked activity in fear extinction− rats than fear extinction+ rats in the spinal nerve ligation model compared to sham controls.ConclusionThe data may suggest that fear extinction learning ability predicts the magnitude of neuropathic pain-related affective rather than sensory behaviors, which correlates with differences in amygdala activity changes.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Fear extinction learning ability predicts neuropathic pain behaviors and amygdala activity in male rats

Yakhnitsa

Kiritoshi

et al. 2018

Mol Pain

Self Cite

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“…6,7 Recently, a significant number of preclinical research groups have focused their attention on the affective symptoms of pain. [8][9][10][11][12] However, the onset, development and maintenance of the affective component remain unclear.…”

Section: Introductionmentioning

confidence: 99%

<p>Proteomics analysis of the amygdala in rats with CFA-induced pain aversion with electro-acupuncture stimulation</p>

Wu¹,

Jiang²,

Shao³

et al. 2019

JPR

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Background: Clinical patients suffering from pain usually exhibit aversion to pain-associated environments (pain aversion). Electro-acupuncture (EA) has been proven to be effective for the treatment of pain aversion in our previous studies. The amygdala could have substantial consequences on emotion and pain consolidation as well as general pain aversion behavior, however, the underlying mechanism remains unclear. Purpose: The current study was performed to investigate Isobaric tags for relative and absolute quantitation (iTRAQ) based quantitative proteomic analysis of the amygdala in rats with complete Freund's adjuvant (CFA)-induced pain aversion, and comprehensive analysis of protein expression were performed to explore the underlying mechanism by which EA affects pain aversion. Materials and methods: Inflammatory pain was induced with an intraplantar injection of 100 μL of CFA in the plantar surface of the left hind paw of the male Spragure-Dawley (SD) rats. Then the CFA-induced conditioned place aversion (C-CPA) test was performed. EA stimulation on the bilateral Zusanli and Sanyinjiao acu-points was used for 14 days and the EA stimulation frequency is 2 Hz. Based on iTRAQ-based proteomics analysis, we investigated the protein expression in the amygdala. Results: EA can increase the paw withdrawal threshold in inflammatory pain induced by noxious stimulation. A total of 6319 proteins were quantified in amygdala. Of these identified proteins, 123 were identified in the pain aversion group relative to those in the saline group, and 125 significantly altered proteins were identified in the pain aversion + EA group relative to the pain aversion group. A total of 11 proteins were found to be differentially expressed in the amygdala of pain aversion and EA-treated rats. The expression of three proteins, glyceraldehyde-3-phosphate dehydrogenase, glutamate transporter-1, and p21-activated kinase 6, were confirmed to be consistent with the results of the proteome. Conclusion: Our investigation demonstrated the possible mechanism of central nerve system by which EA intervetion on pain aversion.

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“…A second common difference across slice electrophysiology experiments is the recording temperature, with studies performing experiments either at room temperature (e.g., Kirson et al, ; de Guglielmo et al, ), or using an in‐line heater to maintain recording aCSF at a more physiologically relevant temperature (e.g., Herman et al, ; Ji et al, ). Recording temperature affects the excitability of neurons in vitro , with greater activity in cells maintained near physiological temperatures (e.g., Cao and Oertel, ; Lee et al, ; Micheva and Smith, ; Graham et al, ; Baginskas et al, ), and was therefore included as an additional variable in our experiments.…”

Section: Introductionmentioning

confidence: 99%

Synaptic GABAergic transmission in the central amygdala (CeA) of rats depends on slice preparation and recording conditions

2019

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The central nucleus of the amygdala (CeA) is a primarily GABAergic brain region implicated in stress and addictive disorders. Using in vitro slice electrophysiology, many studies measure GABAergic neurotransmission to evaluate the impact of experimental manipulations on inhibitory tone in the CeA, as a measure of alterations in CeA activity and function. In a recent study, we reported spontaneous inhibitory postsynaptic current (sIPSC) frequencies higher than those typically reported in CeA neurons in the literature, despite utilizing similar recording protocols and internal recording solutions. The purpose of this study was to systematically evaluate two common methods of slice preparation, an NMDG‐based aCSF perfusion method and an ice‐cold sucrose solution, as well as the use of an in‐line heater to control recording temperature, on measures of intrinsic excitability and spontaneous inhibitory neurotransmission in CeA neurons. We report that both slice preparation and recording conditions significantly impact spontaneous GABAergic transmission in CeA neurons, and that recording temperature, but not slicing solution, alters measures of intrinsic excitability in CeA neurons. Bath application of corticotropin‐releasing factor (CRF) increased sIPSC frequency under all conditions, but the magnitude of this effect was significantly different across recording conditions that elicited different baseline GABAergic transmission. Furthermore, CRF effects on synaptic transmission differed according to data reporting methods (i.e., raw vs. normalized data), which is important to consider in relation to baseline synaptic transmission values. These studies highlight the impact of experimental conditions and data reporting methods on neuronal excitability and synaptic transmission in the CeA.

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5-HT_2CReceptor Knockdown in the Amygdala Inhibits Neuropathic-Pain-Related Plasticity and Behaviors

Cited by 71 publications

References 94 publications

Fear extinction learning ability predicts neuropathic pain behaviors and amygdala activity in male rats

Fear extinction learning ability predicts neuropathic pain behaviors and amygdala activity in male rats

<p>Proteomics analysis of the amygdala in rats with CFA-induced pain aversion with electro-acupuncture stimulation</p>

Synaptic GABAergic transmission in the central amygdala (CeA) of rats depends on slice preparation and recording conditions

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5-HT2CReceptor Knockdown in the Amygdala Inhibits Neuropathic-Pain-Related Plasticity and Behaviors

Cited by 71 publications

References 94 publications

Fear extinction learning ability predicts neuropathic pain behaviors and amygdala activity in male rats

Fear extinction learning ability predicts neuropathic pain behaviors and amygdala activity in male rats

<p>Proteomics analysis of the amygdala in rats with CFA-induced pain aversion with electro-acupuncture stimulation</p>

Synaptic GABAergic transmission in the central amygdala (CeA) of rats depends on slice preparation and recording conditions

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5-HT_2CReceptor Knockdown in the Amygdala Inhibits Neuropathic-Pain-Related Plasticity and Behaviors