RT Journal Article
SR Electronic
T1 Hyperactivity of Anterior Cingulate Cortex Areas 24a/24b Drives Chronic Pain-Induced Anxiodepressive-like Consequences
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 3102
OP 3115
DO 10.1523/JNEUROSCI.3195-17.2018
VO 38
IS 12
A1 Jim Sellmeijer
A1 Victor Mathis
A1 Sylvain Hugel
A1 Xu-Hui Li
A1 Qian Song
A1 Qi-Yu Chen
A1 Florent Barthas
A1 Pierre-Eric Lutz
A1 Meltem Karatas
A1 Andreas Luthi
A1 Pierre Veinante
A1 Ad Aertsen
A1 Michel Barrot
A1 Min Zhuo
A1 Ipek Yalcin
YR 2018
UL http://www.jneurosci.org/content/38/12/3102.abstract
AB Pain associates both sensory and emotional aversive components, and often leads to anxiety and depression when it becomes chronic. Here, we characterized, in a mouse model, the long-term development of these sensory and aversive components as well as anxiodepressive-like consequences of neuropathic pain and determined their electrophysiological impact on the anterior cingulate cortex (ACC, cortical areas 24a/24b). We show that these symptoms of neuropathic pain evolve and recover in different time courses following nerve injury in male mice. In vivo electrophysiological recordings evidence an increased firing rate and bursting activity within the ACC when anxiodepressive-like consequences developed, and this hyperactivity persists beyond the period of mechanical hypersensitivity. Whole-cell patch-clamp recordings also support ACC hyperactivity, as shown by increased excitatory postsynaptic transmission and contribution of NMDA receptors. Optogenetic inhibition of the ACC hyperactivity was sufficient to alleviate the aversive and anxiodepressive-like consequences of neuropathic pain, indicating that these consequences are underpinned by ACC hyperactivity.SIGNIFICANCE STATEMENT Chronic pain is frequently comorbid with mood disorders, such as anxiety and depression. It has been shown that it is possible to model this comorbidity in animal models by taking into consideration the time factor. In this study, we aimed at determining the dynamic of different components and consequences of chronic pain, and correlated them with electrophysiological alterations. By combining electrophysiological, optogenetic, and behavioral analyses in a mouse model of neuropathic pain, we show that the mechanical hypersensitivity, ongoing pain, anxiodepressive consequences, and their recoveries do not necessarily exhibit temporal synchrony during chronic pain processing, and that the hyperactivity of the anterior cingulate cortex is essential for driving the emotional impact of neuropathic pain.