Brain-derived neurotrophic factor (BDNF) in the rostral anterior cingulate cortex (rACC) contributes to neuropathic spontaneous pain-related aversion via NR2B receptors

Zhang, Le; Wang, Gongming; Ma, Jing; Liu, Chengxiao; Liu, Xijiang; Zhan, Yufeng; Zhang, Mengyuan

doi:10.1016/j.brainresbull.2016.08.016

Cited by 28 publications

(21 citation statements)

References 41 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: 42%

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: 42%

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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“…Activation of the ACC is associated with reduced pain behavior produced by unilateral spinal nerve injury in rats34. The ACC is also reported to be involved in the persistent neuropathic pain313839. The nerve cells in ACC responded to noxious stimuli and were activated during pain tested by electrophysiological methods40.…”

Section: Discussionmentioning

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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“…Similarly, increased neuronal activities in the medial prefrontal cortex (including the rostral anterior cingulate) were detected during a sustained high-pain period in patients with chronic back pain (Baliki et al, 2006 ). Other studies applied various chemicals, including ζ-pseudosubstrate inhibitory peptide (ZIP; Li et al, 2010 ), IEM1460 (Liu et al, 2015 ) and clonidine (Zuo et al, 2015 ), to the ACC locally, and unmasking effects on the aversion induced by peripheral nerve injury were observed, whereas lesion (Qu et al, 2011 ) or injection of brain-derived neurotrophic factor (BDNF)–tropomyosin receptor kinase B (TrkB) antagonist into the rostral ACC completely blocked the CPP induced by clonidine (Zhang et al, 2016 ), suggesting that the ACC is necessary for the regulation of spontaneous pain. In the current study, we showed that application of clonidine topically to the ACC is sufficient to alleviate both mechanical allodynia and spontaneous pain at day 7 after nerve injury, and that inhibiting the activities of cingulate α 2A adrenoceptors abolishes the place preference induced by clonidine in CPN-ligated mice, suggesting that the activation of cingulate α 2A adrenoceptors is necessary for the analgesic effects of clonidine on the spontaneous pain.…”

Section: Discussionmentioning

confidence: 99%

Cingulate Alpha-2A Adrenoceptors Mediate the Effects of Clonidine on Spontaneous Pain Induced by Peripheral Nerve Injury

Wang

Zuo

et al. 2017

Front. Mol. Neurosci.

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The anterior cingulate cortex (ACC) is an important brain area for the regulation of neuropathic pain. The α2A adrenoceptor is a good target for pain management. However, the role of cingulate α2A adrenoceptors in the regulation of neuropathic pain has been less studied. In this study, we investigated the involvement of cingulate α2A adrenoceptors in the regulation of neuropathic pain at different time points after peripheral nerve injury in mice. The application of clonidine, either systemically (0.5 mg/kg intraperitoneally) or specifically to the ACC, increased paw withdrawal thresholds (PWTs) and induced conditioned place preference (CPP) at day 7 after nerve injury, suggesting that cingulate α2 adrenoceptors are involved in the regulation of pain-like behaviors. Quantitative real-time PCR data showed that α2A adrenoceptors are the dominant α2 adrenoceptors in the ACC. Furthermore, the expression of cingulate α2A adrenoceptors was increased at day 3 and day 7 after nerve injury, but decreased at day 14, while no change was detected in the concentration of adrenaline or noradrenaline. BRL-44408 maleate, a selective antagonist of α2A adrenoceptors, was microinfused into the ACC. This blocking of cingulate α2A adrenoceptors activity abolished the CPP induced by clonidine (0.5 mg/kg intraperitoneally) but not the effects on PWTs at day 7. However, clonidine applied systemically or specifically to the ACC at day 14 increased the PWTs but failed to induce CPP; this negative effect was reversed by the overexpression of cingulate α2A adrenoceptors. These results suggest that cingulate α2A adrenoceptors are necessary for the analgesic effects of clonidine on spontaneous pain.

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Brain-derived neurotrophic factor (BDNF) in the rostral anterior cingulate cortex (rACC) contributes to neuropathic spontaneous pain-related aversion via NR2B receptors

Cited by 28 publications

References 41 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

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

Cingulate Alpha-2A Adrenoceptors Mediate the Effects of Clonidine on Spontaneous Pain Induced by Peripheral Nerve Injury

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