Key Laboratory of Brain Stress and Behavior

Fengcheng, China

Key Laboratory of Brain Stress and Behavior

Fengcheng, China
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Chen J.,PLA Fourth Military Medical University | Chen J.,Key Laboratory of Brain Stress and Behavior | Chen J.,Beijing Institute for Brain Disorders
Neuroscience Bulletin | Year: 2017

Empathy is traditionally thought to be a unique ability of humans to feel, understand, and share the emotional state of others. However, the notion has been greatly challenged by the emerging discoveries of empathy for pain or distress in rodents. Because empathy is believed to be fundamental to the formation of prosocial, altruistic, and even moral behaviors in social animals and humans, studies associated with decoding the neural circuits and unraveling the underlying molecular and neural mechanisms of empathy for pain or distress in rodents would be very important and encouraging. In this review, the author set out to outline and update the concept of empathy from the evolutionary point of view, and introduce up-to-date advances in the study of empathy and its neural correlates in both humans and rodents. Finally, the author highlights the perspectives and challenges for the further use of rodent models in the study of empathy for pain or distress. © 2017 Shanghai Institutes for Biological Sciences, CAS and Springer Science+Business Media Singapore


Lu Y.-F.,PLA Fourth Military Medical University | Lu Y.-F.,Key Laboratory of Brain Stress and Behavior | Neugebauer V.,Texas Tech University Health Sciences Center | Chen J.,PLA Fourth Military Medical University | And 4 more authors.
Neuroscience Letters | Year: 2016

Reactive oxygen species (ROS), such as superoxide and hydrogen peroxide, play essential roles in physiological plasticity and are also involved in the pathogenesis of persistent pain. Roles of peripheral and spinal ROS in pain have been well established, but much less is known about ROS in the amygdala, a brain region that plays an important role in pain modulation. The present study explored the contribution of ROS in the amygdala to bee venom (BV)-induced pain behaviors. Our data show that the amygdala is activated following subcutaneous BV injection into the left hindpaw, which is reflected in the increased number of c-Fos positive cells in the central and basolateral amygdala nuclei in the right hemisphere. Stereotaxic administration of a ROS scavenger (tempol, 10 mM), NADPH oxidase inhibitor (baicalein, 5 mM) or lipoxygenase inhibitor (apocynin, 10 mM) into the right amygdala attenuated the BV-induced spontaneous licking and lifting behaviors, but had no effect on BV-induced paw flinch reflexes. Our study provides further evidence for the involvement of the amygdala in nociceptive processing and pain behaviors, and that ROS in amygdala may be a potential target for treatment strategies to inhibit pain. © 2016 Elsevier Ireland Ltd.


Yang F.,PLA Fourth Military Medical University | Sun W.,PLA Fourth Military Medical University | Sun W.,Key Laboratory of Brain Stress and Behavior | Luo W.-J.,PLA Fourth Military Medical University | And 8 more authors.
Molecular Neurobiology | Year: 2017

Emerging evidence has demonstrated the involvement of stromal cell-derived factor 1 (SDF1, also known as CXCL12)-CXCR4 signaling in a variety of pain state. However, the underlying mechanisms of SDF1-CXCR4 signaling leading to the maintenance of chronic pain states are poorly understood. In the present study, we sought to explore the role of SDF1-CXCR4 signaling in the forming of neuroplasticity by applying a model of the transition from acute to chronic pain state, named as hyperalgesic priming. Utilizing intraplantar bee venom (BV) injection, we successfully established hyperalgesic priming state and found that peripheral treating with AMD3100, a CXCR4 antagonist, or knocking down CXCR4 by intraganglionar CXCR4 small interfering RNA (siRNA) injection could prevent BV-induced primary mechanical hyperalgesia and hyperalgesic priming. Moreover, we showed that single intraplantar active SDF1 protein injection is sufficient to induce acute mechanical hyperalgesia and hyperalgesic priming through CXC4. Intraplantar coinjection of ERK inhibitor, U0126, and PI3K inhibitor, LY294002, as well as two protein translation inhibitors, temsirolimus and cordycepin, prevented the development of SDF1-induced acute mechanical hyperalgesia and hyperalgesic priming. Finally, on the models of complete Freund’s adjuvant (CFA)-induced chronic inflammatory pain and spared nerve injury (SNI)-induced chronic neuropathic pain, we observed that knock-down of CXCR4 could both prevent the development and reverse the maintenance of chronic pain state. In conclusion, our present data suggested that through regulating ERK and PI3K-AKT pathways-mediated protein translation SDF1-CXCR4 signaling mediates the transition from acute pain to chronic pain state and finally contributes to the development and maintenance of chronic pain. © 2016, Springer Science+Business Media New York.


Liu M.-G.,PLA Fourth Military Medical University | Liu M.-G.,Seoul National University | Chen X.-F.,PLA Fourth Military Medical University | Chen X.-F.,Key Laboratory of Brain Stress and Behavior | And 6 more authors.
Neuroscience Bulletin | Year: 2012

Simultaneous multisite recording using multi-electrode arrays (MEAs) in cultured and acutely-dissociated brain slices and other tissues is an emerging technique in the field of network electrophysiology. Over the past 40 years, great efforts have been made by both scientists and commercial concerns, to advance this technique. The MEA technique has been widely applied to many regions of the brain, retina, heart and smooth muscle in various studies at the network level. The present review starts from the development of MEA techniques and their uses in brain preparations, and then specifically concentrates on the use of MEA recordings in studies of synaptic plasticity at the network level in both the temporal and spatial domains. Because the MEA technique helps bridge the gap between single-cell recordings and behavioral assays, its wide application will undoubtedly shed light on the mechanisms underlying brain functions and dysfunctions at the network level that remained largely unknown due to the technical difficulties before it matured. © Shanghai Institutes for Biological Sciences, CAS and Springer-Verlag Berlin Heidelberg 2012.


Liu M.-G.,PLA Fourth Military Medical University | Liu M.-G.,Seoul National University | Liu M.-G.,King's College | Chen J.,PLA Fourth Military Medical University | And 2 more authors.
Progress in Neurobiology | Year: 2014

Affective disorders and cognitive deficits are common comorbidities of chronic pain in the clinical setting, which severely affect the quality of life of pain patients and impose a great difficulty upon clinical pain therapy. Despite large numbers of human studies examining this issue, there are surprisingly few reports investigating the comorbidities of chronic pain in animal models. This review summarizes and integrates previous reports of animal studies on pain and comorbidity, covering pain-evoked anxiety, depression, attentional deficits, cognitive impairment and locomotor dysfunction in rodents. Moreover, pain-induced alterations in synaptic plasticity are also discussed in terms of long-term potentiation and long-term depression, synaptic transmission, neuronal excitability and structural correlates in 'pain matrix'. Finally, we conclude this review by pointing out some unresolved problems and future research directions. © 2014 Elsevier Ltd.


Yu Y.-Q.,PLA Fourth Military Medical University | Yu Y.-Q.,Key Laboratory of Brain Stress and Behavior | Zhao Z.-Y.,PLA Fourth Military Medical University | Zhao Z.-Y.,Key Laboratory of Brain Stress and Behavior | And 9 more authors.
NeuroMolecular Medicine | Year: 2013

Tetrodotoxin-resistant (TTX-R) sodium channels NaV1.8 and NaV1.9 in dorsal root ganglion (DRG) neurons play important roles in pathological pain. We recently reported that melittin, the major toxin of whole bee venom, induced action potential firings in DRG neurons even in the presence of a high concentration (500 nM) of TTX, indicating the contribution of TTX-R sodium channels. This hypothesis is fully investigated in the present study. After subcutaneous injection of melittin, NaV1.8 and Na V1.9 significantly upregulate mRNA and protein expressions, and related sodium currents also increase. Double immunohistochemical results show that NaV1.8-positive neurons are mainly medium- and small-sized, whereas NaV1.9-positive ones are only small-sized. Antisense oligodeoxynucleotides (AS ODNs) targeting NaV1.8 and Na V1.9 are used to evaluate functional significance of the increased expressions of TTX-R sodium channels. Behavioral tests demonstrate that AS ODN targeting NaV1.9, but not NaV1.8, reverses melittin-induced heat hypersensitivity. Neither NaV1.8 AS ODN nor NaV1.9 AS ODN affects melittin-induced mechanical hypersensitivity. These results provide previously unknown evidence that upregulation of Na V1.9, but not NaV1.8, in small-sized DRG neurons contributes to melittin-induced heat hypersensitivity. Furthermore, melittin-induced biological effect indicates a potential strategy to study properties of TTX-R sodium channels. © 2012 Springer Science+Business Media New York.


Li Z.,PLA Fourth Military Medical University | Li Z.,Key Laboratory of Brain Stress and Behavior | Lu Y.-F.,PLA Fourth Military Medical University | Lu Y.-F.,Key Laboratory of Brain Stress and Behavior | And 15 more authors.
Pain | Year: 2014

Empathy for the pain experience of others can lead to the activation of pain-related brain areas and can even induce aberrant responses to pain in human observers. Recent evidence shows this high-level emotional and cognitive process also exists in lower animals; however, the mechanisms underlying this phenomenon remain unknown. In the present study we found that, after social interaction with a rat that had received subcutaneous injection of bee venom (BV), only the cagemate observer (CO) but not the noncagemate observer (NCO) showed bilateral mechanical hypersensitivity and an enhanced paw flinch reflex following BV injection. Moreover, neuronal activities labeled by c-Fos immunoreactivity in the spinal dorsal horn of CO rats were also significantly increased relative to the control 1 hour after BV injection. A stress-related response can be excluded because serum corticosterone concentration following social interaction with demonstrator rats in pain was not changed in CO rats relative to NCO and isolated control rats. Anxiety can also be excluded because anxiety-like behaviors could be seen in both the CO and NCO rats tested in the open-field test. Finally, bilateral lesions of the medial prefrontal cortex eliminated the enhancement of the BV-induced paw flinch reflex in CO rats, but bilateral lesions of either the amygdala or the entorhinal cortex failed. Together, we have provided another line of evidence for the existence of familiarity-dependent empathy for pain in rats and have demonstrated that the medial prefrontal cortex plays a critical role in processing the empathy-related enhancement of spinal nociception. ©2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.


Chen J.,PLA Fourth Military Medical University | Chen J.,Key Laboratory of Brain Stress and Behavior | Chen J.,Beijing Institute for Brain Disorders | Guan S.-M.,PLA Fourth Military Medical University | And 4 more authors.
Neuroscience Bulletin | Year: 2016

Melittin is a basic 26-amino-acid polypeptide that constitutes 40–60% of dry honeybee (Apis mellifera) venom. Although much is known about its strong surface activity on lipid membranes, less is known about its pain-producing effects in the nervous system. In this review, we provide lines of accumulating evidence to support the hypothesis that melittin is the major pain-producing substance of bee venom. At the psychophysical and behavioral levels, subcutaneous injection of melittin causes tonic pain sensation and pain-related behaviors in both humans and animals. At the cellular level, melittin activates primary nociceptor cells through direct and indirect effects. On one hand, melittin can selectively open thermal nociceptor transient receptor potential vanilloid receptor channels via phospholipase A2-lipoxygenase/cyclooxygenase metabolites, leading to depolarization of primary nociceptor cells. On the other hand, algogens and inflammatory/pro-inflammatory mediators released from the tissue matrix by melittin’s pore-forming effects can activate primary nociceptor cells through both ligand-gated receptor channels and the G-protein-coupled receptor-mediated opening of transient receptor potential canonical channels. Moreover, subcutaneous melittin up-regulates Nav1.8 and Nav1.9 subunits, resulting in the enhancement of tetrodotoxin-resistant Na+ currents and the generation of long-term action potential firing. These nociceptive responses in the periphery finally activate and sensitize the spinal dorsal horn pain-signaling neurons, resulting in spontaneous nociceptive paw flinches and pain hypersensitivity to thermal and mechanical stimuli. Taken together, it is concluded that melittin is the major pain-producing substance of bee venom, by which peripheral persistent pain and hyperalgesia (or allodynia), primary nociceptive neuronal sensitization, and CNS synaptic plasticity (or metaplasticity) can be readily induced and the molecular and cellular mechanisms underlying naturally-occurring venomous biotoxins can be experimentally unraveled. © 2016 Shanghai Institutes for Biological Sciences, CAS and Springer Science+Business Media Singapore


Yu Y.-Q.,PLA Fourth Military Medical University | Yu Y.-Q.,Beijing Institute for Brain Disorders | Chen X.-F.,PLA Fourth Military Medical University | Chen X.-F.,Beijing Institute for Brain Disorders | And 7 more authors.
Physiological Research | Year: 2014

In the mammalian autonomic nervous system, tonic and phasic neurons can be differentiated on firing patterns in response to long depolarizing current pulse. However, the similar firing patterns in the somatic primary sensory neurons and their functional significance are not well investigated. Here, we identified two types of neurons innervating somatic sensory in rat dorsal root ganglia (DRG). Tonic neurons fire action potentials (APs) in an intensity-dependent manner, whereas phasic neurons typically generate only one AP firing at the onset of stimulation regardless of intensity. Combining retrograde labeling of somatic DRG neurons with fluorescent tracer DiI, we further find that these neurons demonstrate distinct changes under inflammatory pain states induced by complete Freund's adjuvant (CFA) or bee venom toxin melittin. In tonic neurons, CFA and melittin treatments significantly decrease rheobase and AP durations (depolarization and repolarization), enhance amplitudes of overshoot and afterhyperpolarization (AHP), and increase the number of evoked action potentials. In phasic neurons, however, the same inflammation treatments cause fewer changes in these electrophysiological parameters except for the increased overshoot and decreased AP durations. In the present study, we find that tonic neurons are more hyperexcitable than phasic neurons after peripheral noxious inflammatory stimulation. The results indicate the distinct contributions of two types of DRG neurons in inflammatory pain. © 2014 Institute of Physiology v.v.i.


Xie F.,PLA Fourth Military Medical University | Xie F.,Key Laboratory of Brain Stress and Behavior | Fu H.,PLA Fourth Military Medical University | Fu H.,Key Laboratory of Brain Stress and Behavior | And 5 more authors.
PLoS ONE | Year: 2013

To establish the role of the metabolic state in the pathogenesis of polyneuropathy, an age- and sex-matched, longitudinal study in rats fed high-fat and high-sucrose diets (HFSD) or high-fat, high-sucrose and high-salt diets (HFSSD) relative to controls was performed. Time courses of body weight, systolic blood pressure, fasting plasma glucose (FPG), insulin, free fatty acids (FFA), homeostasis model assessment-insulin resistance index (HOMA-IR), thermal and mechanical sensitivity and motor coordination were measured in parallel. Finally, large and small myelinated fibers (LMF, SMF) as well as unmyelinated fibers (UMF) in the sciatic nerves and ascending fibers in the spinal dorsal column were quantitatively assessed under electron microscopy. The results showed that early metabolic syndrome (hyperinsulinemia, dyslipidemia, and hypertension) and prediabetic conditions (impaired fasting glucose) could be induced by high energy diet, and these animals later developed painful polyneuropathy characterized by myelin breakdown and LMF loss in both peripheral and central nervous system. In contrast SMF and UMF in the sciatic nerves were changed little, in the same animals. Therefore the phenomenon that high energy diets induce bilateral mechanical, but not thermal, pain hypersensitivity is reflected by severe damage to LMF, but mild damage to SMF and UMF. Moreover, dietary sodium (high-salt) deteriorates the neuropathic pathological process induced by high energy diets, but paradoxically high salt consumption, may reduce, at least temporarily, chronic pain perception in these animals. © 2013 Xie et al.

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