2015
DOI: 10.1038/ncomms8660
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Deactivation of excitatory neurons in the prelimbic cortex via Cdk5 promotes pain sensation and anxiety

Abstract: The medial prefrontal cortex (mPFC) is implicated in processing sensory-discriminative and affective pain. Nonetheless, the underlying mechanisms are poorly understood. Here we demonstrate a role for excitatory neurons in the prelimbic cortex (PL), a sub-region of mPFC, in the regulation of pain sensation and anxiety-like behaviours. Using a chronic inflammatory pain model, we show that lesion of the PL contralateral but not ipsilateral to the inflamed paw attenuates hyperalgesia and anxiety-like behaviours in… Show more

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Cited by 168 publications
(174 citation statements)
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“…Accordingly, we did not observe a significant increase in the protein levels of the P2X2aR in immunoblots when the receptor was co-expressed with p35 or Cdk5, however future studies will be conducted to explore P2X2aR trafficking to the plasma membrane when Cdk5 is highly activated. There is evidence showing that Cdk5 regulate the activation of several ion channels and membrane receptors, suggesting a role during peripheral and central sensitization in pain pathways [21; 47; 52; 60]: For example Cdk5 can phosphorylate NMDA receptors at Ser1232 of the NR2A subunit [32] and regulate its surface expression through NR2B subunit phosphorylation [44]. P/Q-type voltage-dependent Ca 2+ channels are also targets for Cdk5 phosphorylation, a process that regulates neurotransmitter release [51].…”
Section: Discussionmentioning
confidence: 99%
“…Accordingly, we did not observe a significant increase in the protein levels of the P2X2aR in immunoblots when the receptor was co-expressed with p35 or Cdk5, however future studies will be conducted to explore P2X2aR trafficking to the plasma membrane when Cdk5 is highly activated. There is evidence showing that Cdk5 regulate the activation of several ion channels and membrane receptors, suggesting a role during peripheral and central sensitization in pain pathways [21; 47; 52; 60]: For example Cdk5 can phosphorylate NMDA receptors at Ser1232 of the NR2A subunit [32] and regulate its surface expression through NR2B subunit phosphorylation [44]. P/Q-type voltage-dependent Ca 2+ channels are also targets for Cdk5 phosphorylation, a process that regulates neurotransmitter release [51].…”
Section: Discussionmentioning
confidence: 99%
“…It is interesting to note that neuronal activity in the mPFC, especially the PrLC and ILC, can be inhibited by a GABAergic enhancing mechanism under some pathological pain conditions in animal models of joint arthritis, peripheral neuropathy, and visceral pain [14,[48][49][50]. Moreover, deactivation of excitatory neurons in the PrLC via Cdk5 (cyclin-dependent kinase 5) promotes pain sensation and anxiety [13]. In contrast, optogenetic activation of excitatory pyramidal neurons in the PrLC reverses the GABA-mediated inhibitory state, improving both the sensory and affective aspects of pain [13,14,50,51].…”
Section: Involvement Of Mpfc In Top-down Facilitation Of Mechanical Pmentioning
confidence: 99%
“…Moreover, deactivation of excitatory neurons in the PrLC via Cdk5 (cyclin-dependent kinase 5) promotes pain sensation and anxiety [13]. In contrast, optogenetic activation of excitatory pyramidal neurons in the PrLC reverses the GABA-mediated inhibitory state, improving both the sensory and affective aspects of pain [13,14,50,51]. Besides, pharmacological activation of the ILC output with a combination of metabotropic glutamate receptor 5 (mGluR5) and cannabinoid receptor type 1 (CB1) activators inhibits pain-related behavior and restores decisionmaking in an arthritis model of pain [52].…”
Section: Involvement Of Mpfc In Top-down Facilitation Of Mechanical Pmentioning
confidence: 99%
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“…Studies in rodents have implicated several key brain regions in the development of anxiety-like behavior specifically, the basolateral nucleus of the amygdala (BLA) (Hitchcock and Davis 1986; LeDoux et al 1990; Maren 1999, Davis and Whalen 2001, Moscarello and LeDoux 2013) and the prelimbic (PL) subdivision of the prefrontal cortex (PFC) (Morgan and LeDoux 1995; Gewirtz et al 1997; Corcoran and Quirk 2007; Bravo-Rivera et al 2014; Wang et al 2015). Synaptic plasticity between the BLA and the PL cortex, at least in part, underlies emotional learning and memory (Rosenkranz et al 2003; Maroun Richter-Levin 2003; Vouimba and Maroun 2011).…”
Section: Introductionmentioning
confidence: 99%