Background & Objectives:

Chronic neuropathic pain is a highly prevalent, disabling, and costly pain syndrome which is associated with debilitating psychological co-morbidities related to abnormal fear learning. The lateral amygdala has been shown to play a key role in integrating the sensory components of fear memory and both the acquisition and expression of conditioned fear. However, little is known about how fear learning and its associated brain regions are affected by animal neuropathic pain models.

Methods:

Adult male C57BL/6 mice underwent either chronic constriction injury (CCI) or control sham surgery. Mice were then subjected to a Pavlovian fear conditioning protocol, and the extent of fear-induced freezing behaviour was quantified to determine changes in fear learning and extinction. A separate cohort of CCI and sham mice was used in brain slice electrophysiology experiments to examine synaptic transmission onto lateral amygdala neurons.

Findings:

Following fear conditioning, CCI but not control mice displayed disrupted expression of fear learning and extinction. Unlike sham mice, evoked AMPAR-mediated excitatory postsynaptic currents (EPSCs) in CCI mice displayed inward rectification, indicating the expression of calcium-permeable, GluR2-lacking receptors. In addition, evoked EPSCs in CCI mice displayed a decrease in the AMPA paired-pulse ratio, indicating altered presynaptic excitability.

Conclusion:

These findings suggest that chronic neuropathic pain disrupts fear memory and is associated with pre- and postsynaptic modifications in the lateral amygdala, a crucial substrate for this learning process.