Long-term behavioral profiling of spared nerve injury chronic neuropathic pain mouse model

Chronic neuropathic pain (NP) is a severe neurological condition with significant clinical relevance. Beyond sensory discomfort, it leads to cognitive and emotional disorders, lowering patients’ quality of life. Although this comorbidity is clinically recognized, the mechanisms linking persistent pain and cognitive/emotional issues remain uncertain. The spared nerve injury of the sciatic nerve (SNI) is a model used to study long-term consequences of NP in rodents. Research often focuses on time-periods close to peripheral nerve injury. To understand better the long-term behavioral impact of SNI intervention we evaluated animal behavior from one to four months post-lesion (PL), confirming robust and sustained mechanical allodynia throughout. Working memory and sociability showed no significant differences between groups at any time point. Locomotion in the open field test was reduced at one and two months PL but normalized by month three PL, when reduced relative center exploration emerged. At four months, anxiety-like and repetitive behaviors were normal, except for a selective reduction in induced grooming duration. Our previous work showed no neurodegeneration in cortical and hippocampal regions, while expression of the RNA-binding protein TDP-43, critical for neuronal function, appeared altered in select areas. These results indicate that SNI induces subtle, time-specific behavioral and molecular changes, without overt neurodegeneration or generalized impairment.