Pharmacological restoration of anti-nociceptive functions in the prefrontal cortex relieves chronic pain

Talay, Robert; Liu, Yaling; Michael, Matthew; Li, Anna; Friesner, Isabel D.; Zeng, Fei; Sun, Guanghao; Chen, Zhe; Zhang, Qiaosheng; Wang, Jing

doi:10.1016/j.pneurobio.2021.102001

Cited by 11 publications

(15 citation statements)

References 96 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We then examined the average peak ΔF of Ca 2+ activity in response to both non-noxious and noxious stimuli and found that peak fluorescence was significantly higher in response to noxious stimuli than non-noxious stimuli ( Figure 1I ). These results are compatible with previous findings that suggest neurons in the PFC increase their firing rates in response to noxious stimuli ( Dale et al, 2018 ; Talay et al, 2021 ). Furthermore, the number of neurons that responded to the noxious stimulus was greater than the number of neurons responsive to the non-noxious stimulus ( Figures 1J – 1L ).…”

Section: Resultssupporting

confidence: 93%

“…The prefrontal cortex (PFC) integrates sensory inputs and in turn provides both top-down and cortico-cortical regulation of such inputs ( Salzman and Fusi, 2010 ). Recent studies indicate that neurons in the PFC can increase their firing rates in response to noxious stimuli, but such response is diminished by the presence of chronic pain ( Dale et al, 2018 ; Ji and Neugebauer, 2011 ; Kelly et al, 2016 ; Radzicki et al, 2017 ; Talay et al, 2021 ; Zhang et al, 2015 ). In vitro studies in rodent models have further demonstrated decreased excitability of pyramidal neurons in the PFC under chronic pain conditions ( Ji and Neugebauer, 2011 ; Kelly et al, 2016 ; Radzicki et al, 2017 ; Zhang et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Disrupted population coding in the prefrontal cortex underlies pain aversion

Liu

Zhang

et al. 2021

Cell Reports

Self Cite

View full text Add to dashboard Cite

SUMMARY The prefrontal cortex (PFC) regulates a wide range of sensory experiences. Chronic pain is known to impair normal neural response, leading to enhanced aversion. However, it remains unknown how nociceptive responses in the cortex are processed at the population level and whether such processes are disrupted by chronic pain. Using in vivo endoscopic calcium imaging, we identify increased population activity in response to noxious stimuli and stable patterns of functional connectivity among neurons in the prelimbic (PL) PFC from freely behaving rats. Inflammatory pain disrupts functional connectivity of PFC neurons and reduces the overall nociceptive response. Interestingly, ketamine, a well-known neuromodulator, restores the functional connectivity among PL-PFC neurons in the inflammatory pain model to produce anti-aversive effects. These results suggest a dynamic resource allocation mechanism in the prefrontal representations of pain and indicate that population activity in the PFC critically regulates pain and serves as an important therapeutic target.

show abstract

Section: Resultssupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Disrupted population coding in the prefrontal cortex underlies pain aversion

Liu

Zhang

et al. 2021

Cell Reports

Self Cite

View full text Add to dashboard Cite

show abstract

“…No neurological diseases have been found to be specifically associated with presynaptic AMPAR dysfunction. However, the most recent progresses in this field have shown that the modulation of the activity of AMPARs is effective in chronic pain therapy [ 94 , 95 , 104 ]. Worthy of notice is the recent literature showing that the enhancement of glutamate signaling by AMPAkines, a class of agents that specifically potentiate the function of AMPAR, reduce acute and chronic pain [ 104 , 105 , 106 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, the most recent progresses in this field have shown that the modulation of the activity of AMPARs is effective in chronic pain therapy [ 94 , 95 , 104 ]. Worthy of notice is the recent literature showing that the enhancement of glutamate signaling by AMPAkines, a class of agents that specifically potentiate the function of AMPAR, reduce acute and chronic pain [ 104 , 105 , 106 ]. In addition, recent studies indicate that AMPAkines may have an antidepressant effect [ 107 , 108 , 109 ] and that they may influence memory in a mouse model of intellectual disability [ 110 ].…”

Section: Discussionmentioning

confidence: 99%

Presynaptic AMPA Receptors in Health and Disease

Zanetti

Regoni

Ratti

et al. 2021

Cells

View full text Add to dashboard Cite

AMPA receptors (AMPARs) are ionotropic glutamate receptors that play a major role in excitatory neurotransmission. AMPARs are located at both presynaptic and postsynaptic plasma membranes. A huge number of studies investigated the role of postsynaptic AMPARs in the normal and abnormal functioning of the mammalian central nervous system (CNS). These studies highlighted that changes in the functional properties or abundance of postsynaptic AMPARs are major mechanisms underlying synaptic plasticity phenomena, providing molecular explanations for the processes of learning and memory. Conversely, the role of AMPARs at presynaptic terminals is as yet poorly clarified. Accruing evidence demonstrates that presynaptic AMPARs can modulate the release of various neurotransmitters. Recent studies also suggest that presynaptic AMPARs may possess double ionotropic-metabotropic features and that they are involved in the local regulation of actin dynamics in both dendritic and axonal compartments. In addition, evidence suggests a key role of presynaptic AMPARs in axonal pathology, in regulation of pain transmission and in the physiology of the auditory system. Thus, it appears that presynaptic AMPARs play an important modulatory role in nerve terminal activity, making them attractive as novel pharmacological targets for a variety of pathological conditions.

show abstract

“…The medial and dorsolateral prefrontal cortices (PFC) and the anterior cingulate cortex (ACC) play critical roles in acute and chronic pain modulation. Previous studies have shown that acute noxious stimuli could induce an increase in neuronal firing in those regions (7)(8)(9)(10). The PFC is an important center for top-down regulation of sensory stimuli (11).…”

Section: Introductionmentioning

confidence: 99%

Frequency Dependent Electrical Stimulation of PFC and ACC for Acute Pain Treatment in Rats

Liu

Sun

et al. 2021

Front. Pain Res.

Self Cite

View full text Add to dashboard Cite

As pain consists of both sensory and affective components, its management by pharmaceutical agents remains difficult. Alternative forms of neuromodulation, such as electrical stimulation, have been studied in recent years as potential pain treatment options. Although electrical stimulation of the brain has shown promise, more research into stimulation frequency and targets is required to support its clinical applications. Here, we studied the effect that stimulation frequency has on pain modulation in the prefrontal cortex (PFC) and the anterior cingulate cortex (ACC) in acute pain models in rats. We found that low-frequency stimulation in the prelimbic region of the PFC (PL-PFC) provides reduction of sensory and affective pain components. Meanwhile, high-frequency stimulation of the ACC, a region involved in processing pain affect, reduces pain aversive behaviors. Our results demonstrate that frequency-dependent neuromodulation of the PFC or ACC has the potential for pain modulation.

show abstract

Pharmacological restoration of anti-nociceptive functions in the prefrontal cortex relieves chronic pain

Cited by 11 publications

References 96 publications

Disrupted population coding in the prefrontal cortex underlies pain aversion

Disrupted population coding in the prefrontal cortex underlies pain aversion

Presynaptic AMPA Receptors in Health and Disease

Frequency Dependent Electrical Stimulation of PFC and ACC for Acute Pain Treatment in Rats

Contact Info

Product

Resources

About