Role of the Anterior Cingulate Cortex in Translational Pain Research

Xiao, Xiao; Ding, Ming; Zhang, Yu‐Qiu

doi:10.1007/s12264-020-00615-2

Cited by 53 publications

(29 citation statements)

References 239 publications

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“…Instead, the advent of deep brain stimulation (DBS) provides a promising alternative for modifying dysfunctional pain-matrix activity in the treatment of refractory pain disorders, surpassing lesion surgery due to its adjustability and reversibility [65]. The ACC is a newly-identified stimulation spot for the treatment of drug-resistant depression [66] and chronic pain [67]. Bilateral ACC DBS is known to relieve various types of neuropathic pain and restore quality of life; it outperforms periaqueductal gray or thalamus stimulation by targeting the affective component of pain [66].…”

Section: Neuromodulation Techniques Targeting the Acc As A Viable Therapy For Painful Cpmentioning

confidence: 99%

Anterior Cingulate Cortex Mediates Hyperalgesia and Anxiety Induced by Chronic Pancreatitis in Rats

Ren

Qiu

et al. 2021

Neurosci. Bull.

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Central sensitization is essential in maintaining chronic pain induced by chronic pancreatitis (CP), but cortical modulation of painful CP remains elusive. Here, we examined the role of the anterior cingulate cortex (ACC) in the pathogenesis of abdominal hyperalgesia in a rat model of CP induced by intraductal administration of trinitrobenzene sulfonic acid (TNBS). TNBS treatment resulted in long-term abdominal hyperalgesia and anxiety in rats. Morphological data indicated that painful CP induced a significant increase in FOS-expressing neurons in the nucleus tractus solitarii (NTS) and ACC, and some FOS-expressing neurons in the NTS projected to the ACC. In addition, a larger portion of ascending fibers from the NTS innervated pyramidal neurons, the neural subpopulation primarily expressing FOS under the condition of painful CP, rather than GABAergic neurons within the ACC. CP rats showed increased expression of vesicular glutamate transporter 1, and increased membrane trafficking and phosphorylation of the N-methyl-D-aspartate receptor (NMDAR) subunit NR2B and the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) subunit GluR1 within the ACC. Microinjection of NMDAR and AMPAR antagonists into the ACC to block excitatory synaptic transmission significantly attenuated abdominal hyperalgesia in CP rats, which was similar to the analgesic effect of endomorphins injected into the ACC. Specifically inhibiting the excitability of ACC pyramidal cells via chemogenetics reduced both hyperalgesia and comorbid anxiety, whereas activating these neurons via optogenetics failed to aggravate hyperalgesia and anxiety in CP rats. Taken together, these findings provide neurocircuit, biochemical, and behavioral evidence for involvement of the ACC in hyperalgesia and anxiety in CP rats, as well as novel insights into the cortical modulation of painful CP, and highlights the ACC as a potential target for neuromodulatory interventions in the treatment of painful CP.

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Section: Neuromodulation Techniques Targeting the Acc As A Viable Therapy For Painful Cpmentioning

confidence: 99%

Anterior Cingulate Cortex Mediates Hyperalgesia and Anxiety Induced by Chronic Pancreatitis in Rats

Ren

Qiu

et al. 2021

Neurosci. Bull.

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“…The anterior cingulate cortex (ACC) is a critical limbic site for the regulation of pain perception [26], which is involved in the process of sensory information and pain aversion [5,27]. Peripheral nerve injury increases excitatory synaptic transmissions [28] or changes the intrinsic properties of intermediate neurons in the ACC; these changes contribute to peripheral hypersensitivity via descending control of the spinal cord [29].…”

Section: Ltd Induction In the Somatosensory Pathway Is Dependent On T...mentioning

confidence: 99%

Targeting long‐term depression of excitatory synaptic transmission for the treatment of neuropathic pain

Wang

Lian

et al. 2021

The FEBS Journal

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Injury or disease in the somatosensory nervous system may cause broad molecular changes and lead to neuropathic pain. Excitatory synaptic transmission in somatosensory pathways conveys the somatosensory information from the peripheral to the central nervous system. Long-term effects of excitatory synaptic transmission on the pain pathway contribute to neuropathic pain hypersensitivity. Synaptic strength is dynamically regulated and undergoes bidirectional changes, manifested by two primary forms of synaptic plasticity, long-term potentiation and long-term depression (LTD), which are mediated by insertion and endocytosis of amino-3hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), respectively. Molecular mechanisms of LTP have been extensively studied; on the other hand, the role of AMPAR endocytosis in the pain-related synaptic enhancement is less well known. Recent research in the anterior cingulate cortex reveals that loss of LTD contributes to the maintenance of neuropathic pain, which provides the novel perspective of the mechanism of LTD also being critical for maintaining neuropathic pain. More importantly, exploring the molecular mechanism of LTD may help with the development of novel analgesic strategies to manage neuropathic pain.

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“…The significant regions of the superior thalamic radiations terminate in the posterior cingulate (PCC), a key node within the default-mode network (DMN), a system of connected regions that mediate self-referential thinking and rumination ( Mak et al, 2017 ). While the anterior cingulate is more commonly implicated in pain processing ( Tsuda et al, 2017 , Xiao et al, 2021 ), some studies have specifically targeted PCC. A weaker connection between PCC and the rest of the DMN has been found to predict a stronger pain experience in both CP patients and HCs ( Alshelh et al, 2018 , Loggia et al, 2013 ).…”

Section: Discussionmentioning

confidence: 99%

White matter microstructure predicts measures of clinical symptoms in chronic back pain patients

Robertson

Aristi

Hashmi

2023

NeuroImage: Clinical

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Role of the Anterior Cingulate Cortex in Translational Pain Research

Cited by 53 publications

References 239 publications

Anterior Cingulate Cortex Mediates Hyperalgesia and Anxiety Induced by Chronic Pancreatitis in Rats

Anterior Cingulate Cortex Mediates Hyperalgesia and Anxiety Induced by Chronic Pancreatitis in Rats

Targeting long‐term depression of excitatory synaptic transmission for the treatment of neuropathic pain

White matter microstructure predicts measures of clinical symptoms in chronic back pain patients

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