I am a
Home I AM A Search Login

Papers of the Week

Papers: 7 Sep 2019 - 13 Sep 2019

Animal Studies

2019 Oct

Nat Neurosci



Editor's Pick

A neuronal circuit for activating descending modulation of neuropathic pain.


Huang J, Gadotti VM, Chen L, Souza IA, Huang S, Wang D, Ramakrishnan C, Deisseroth K, Zhang Z, Zamponi GW
Nat Neurosci. 2019 Oct; 22(10):1659-1668.
PMID: 31501573.


Neuropathic pain can be a debilitating condition with both sensory and affective components, the underlying brain circuitry of which remains poorly understood. In the present study, a basolateral amygdala (BLA)-prefrontal cortex (PFC)-periaqueductal gray (PAG)-spinal cord pathway was identified that is critical for the development of mechanical and thermal hypersensitivity after peripheral nerve injury. It was shown that nerve injury strengthens synaptic input from the BLA onto inhibitory interneurons located in the prelimbic medial PFC, by virtue of reduced endocannabinoid modulation. These augmented synaptic connections mediate a feedforward inhibition of projections from the PFC to the ventrolateral PAG region and its downstream targets. Optogenetic approaches combined with in vivo pharmacology reveal that these BLA-PFC-PAG connections alter pain behaviors by reducing descending noradrenergic and serotoninergic modulation of spinal pain signals. Thus, a long-range brain circuit was identified that is crucial for pain processing and that can potentially be exploited toward targeting neuropathic pain.