Inhibition of mammalian target of rapamycin activation in the rostral anterior cingulate cortex attenuates pain-related aversion in rats

Lu, Bo; Jiang, Jingyan; Sun, Jiao; Xiao, Chengshan; Meng, Bo; Zheng, Jinwei; Li, Xiaoyü; Wang, Ruichun; Wu, Guorong; Chen, Junping

doi:10.1016/j.bbr.2016.05.011

Cited by 10 publications

(7 citation statements)

References 44 publications

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“…The C-CPA test is based on associative learning between a painful stimulus aversion and the environmental context in which the stimulus is administered; the inhibition of pain-related aversive behavior may be caused by a disruption of various forms of long-term memory. 15 , 16 In our study, C-CPA was gradually attenuated to the baseline level over 4 weeks, but we still observed significant aversion to the pain-paired compartment in the CFA-injected group compared to the saline group. These findings indicate that the association between the painful stimulus aversion and the environmental context was weakened over time.…”

Section: Discussionmentioning

confidence: 43%

“… 10 – 12 The conditioned-place aversion (CPA) paradigm is a highly sensitive method for measuring the negative effect of an aversive memory associated with a pain-paired context. 13 – 16 Recent studies have shown that the affective component of chronic inflammatory pain can be assessed with a CPA test (pain aversion) and other emotional behavior tests, such as the elevated zero maze (EZM) and open field (OF) tests. 17 , 18 However, the onset, development, and maintenance of the affective component remain unclear.…”

Section: Introductionmentioning

confidence: 99%

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Pain aversion and anxiety-like behavior occur at different times during the course of chronic inflammatory pain in rats

Wu¹,

Yao²,

Jiang³

et al. 2017

JPR

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Pain is considered a multidimensional conscious experience that includes a sensory component and a negative affective-motivational component. The negative affective-motivational component of pain is different from the sensory component and amplifies the pain experience. Nowadays, a significant number of preclinical research groups have focused their attention on the affective symptoms of pain. In the present study, we investigated the pain aversion and anxiety-like behavior of the complete Freund’s adjuvant (CFA)-induced chronic pain model. CFA rats experienced spontaneous pain during pain-paired conditioning (pain aversion) and spontaneous pain produces an affective response (anxiety-like behavior). Moreover, pain aversion was gradually attenuated, while the anxiety-like behavior increased in 4 weeks. Therefore, although the negative effect (including pain aversion and anxiety) is always associated with hyperalgesia, the manifestations of negative effect may follow different time courses, which may influence the progress of primary disease. The findings illustrate that targeted therapy should focus on a specific aspect in different stages of pain. Our study emphasizes the necessity of using multiple tests to study pain comorbidities.

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Section: Discussionmentioning

confidence: 43%

Section: Introductionmentioning

confidence: 99%

Pain aversion and anxiety-like behavior occur at different times during the course of chronic inflammatory pain in rats

Wu¹,

Yao²,

Jiang³

et al. 2017

JPR

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“…Previous studies report increased activity of mTOR and its downstream effectors in the spinal cord dorsal horn in the chronic constriction injury model [ 44 ], the rostral ventromedial medulla in the spared nerve injury model [ 45 ], and the IC in the nerve-injured model [ 34 ]. Also, another study reports increased expression of p-mTOR and p-p70S6K in the ACC of a formalin-induced inflammatory animal model [ 46 ]. Together with previous studies, our results demonstrate that the mTOR-dependent signaling pathway in the ACC is involved in the development of chronic pain.…”

Section: Discussionmentioning

confidence: 99%

Pain-Relieving Effects of mTOR Inhibitor in the Anterior Cingulate Cortex of Neuropathic Rats

Kim

Leem

et al. 2018

Mol Neurobiol

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The anterior cingulate cortex (ACC) is a well-known brain area that is associated with pain perception. Previous studies reported that the ACC has a specific role in the emotional processing of pain. Chronic pain is characterized by long-term potentiation that is induced in pain pathways and contributes to hyperalgesia caused by peripheral nerve injury. The mammalian target of rapamycin (mTOR) signaling, which is involved in synaptic protein synthesis, could be a key factor controlling long-term potentiation in neuropathic pain conditions. Until now, there have been no reports that studied the role of mTOR signaling in the ACC involved in neuropathic pain. Therefore, this study was conducted to determine the relationship of mTOR signaling in the ACC and neuropathic pain. Male Sprague-Dawley rats were subjected to cannula implantation and nerve injury under pentobarbital anesthesia. Microinjection with rapamycin into the ACC was conducted under isoflurane anesthesia on postoperative day (POD) 7. A behavioral test was performed to evaluate mechanical allodynia, and optical imaging was conducted to observe the neuronal responses of the ACC to peripheral stimulation. Inhibition of mTOR by rapamycin reduced mechanical allodynia, down-regulated mTOR signaling in the ACC, and diminished the expressions of synaptic proteins which are involved in excitatory signaling, thereby reducing neuropathic pain-induced synaptic plasticity. These results suggest that inhibiting mTOR activity by rapamycin in the ACC could serve as a new strategy for treating or managing neuropathic pain before it develops into chronic pain.

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“…Recently, many studies demonstrated that ACC is involved in the nociceptive modulation in the brain2526272829303132. Neuropathic pain is one of common clinic pain131633.…”

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confidence: 99%

Involvement of galanin and galanin receptor 2 in nociceptive modulation in anterior cingulate cortex of normal rats and rats with mononeuropathy

Zhang

Wang

et al. 2017

Sci Rep

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The present study was performed to explore the role of galanin and galanin receptor 2 in nociceptive modulation in anterior cingulate cortex (ACC) of normal rats and rats with mononeuropathy. Intra-ACC injection of galanin induced significant increases in hindpaw withdrawal latencies (HWLs) to thermal and mechanical stimulations in both normal rats and rats with mononeuropathy, the increased HWLs were attenuated significantly by intra-ACC injection of galanin receptor 2 antagonist M871, indicating an involvement of galanin receptor 2 in nociceptive modulation in ACC. Interestingly, the galanin-induced HWL was significant higher in rats with mononeuropathy than that in normal rats tested by Randall Selitto test. Furthermore, both the galanin mRNA expression and galanin content increased significantly in ACC in rats with mononeuropathy than that in normal rats. Moreover, both the mRNA levels of galanin receptor 2 and the content of galanin receptor 2 in ACC increased significantly in rats with mononeuropathy than that in normal rats. These results found that galanin induced antinociception in ACC in both normal rats and rats with mononeuropathy. And there may be plastic changes in the expression of galanin and galanin receptor 2 in rats with mononeuropathy, as well as in the galanin-induced antinociception.

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Inhibition of mammalian target of rapamycin activation in the rostral anterior cingulate cortex attenuates pain-related aversion in rats

Cited by 10 publications

References 44 publications

Pain aversion and anxiety-like behavior occur at different times during the course of chronic inflammatory pain in rats

Pain aversion and anxiety-like behavior occur at different times during the course of chronic inflammatory pain in rats

Pain-Relieving Effects of mTOR Inhibitor in the Anterior Cingulate Cortex of Neuropathic Rats

Involvement of galanin and galanin receptor 2 in nociceptive modulation in anterior cingulate cortex of normal rats and rats with mononeuropathy

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