Long-term neuropathic pain behaviors correlate with synaptic plasticity and limbic circuit alteration: a comparative observational study in mice

Abstract

Neuropathic pain has long-term consequences in affective and cognitive disturbances, suggesting the involvement of supraspinal mechanisms. In this study, we used the spared nerve injury (SNI) model to characterize the development of sensory and aversive components of neuropathic pain and to determine their electrophysiological impact across prefrontal cortex and limbic regions. Moreover, we evaluated the regulation of several genes involved in immune response and inflammation triggered by SNI. We showed that SNI led to sensorial hypersensitivity (cold and mechanical stimuli) and depressive-like behavior lasting 12 months after nerve injury. Of interest, changes in nonemotional cognitive tasks (novel object recognition and Y maze) showed in 1-month SNI mice were not evident normal in the 12-month SNI animals. In vivo electrophysiology revealed an impaired long-term potentiation at prefrontal cortex-nucleus accumbens core pathway in both the 1-month and 12-month SNI mice. On the other hand, a reduced neural activity was recorded in the lateral entorhinal cortex-dentate gyrus pathway in the 1-month SNI mice, but not in the 12-month SNI mice. Finally, we observed the upregulation of specific genes involved in immune response in the hippocampus of 1-month SNI mice, but not in the 12-month SNI mice, suggesting a neuroinflammatory response that may contribute to the SNI phenotype. These data suggest that distinct brain circuits may drive the psychiatric components of neuropathic pain and pave the way for better investigation of the long-term consequences of peripheral nerve injury for which most of the available drugs are to date unsatisfactory.

Unbiased analysis of the dorsal root ganglion after peripheral nerve injury: no neuronal loss, no gliosis, but satellite glial cell plasticity

“…Animals develop robust allodynia and pain-like behavior that last for months after the tibioperoneal nerves are cut at SNI. 16 , 20 , 59 In line with other studies, 17 , 27 , 32 , 37 , 65 we focused on early plasticity responses (7, 14 days) after nerve injury. Early responses are also observed in injury models of the central nervous system.…”

A Prospective Study of Chronic Postsurgical Pain in Elderly Patients: Prevalence, Characteristics and Risk factors

“…In this study, the rate of CPSP with neuropathic component was lower than those reported in studies in young adult and pediatric patients [29,30], although direct comparisons are not possible because of difference in patient characteristics. The protective impact of aging on the occurrence of neuropathic pain has been indicated in animal experiment, and the possible mechanisms include thickness of nerve sheath, nerve injury, and weaker glial activation [31].…”

Effect of TGF-β1-Mediated Exercise Analgesia in Spared Nerve Injury Mice

“…Mechanical and cold allodynia occurred on the 3rd and 4th days after SNI surgery, respectively, and the allodynia was maintained until the end of the experiment. Previous studies have shown that the SNI model induced mechanical and cold allodynia for 12 months [ 25 ], which is suitable for the study of the effect of long-term regular exercise on pain. Studies have shown that high-intensity exercise has a better analgesic effect than low-intensity exercise [ 26 ], but excessive high-intensity exercise may aggravate pain in mice [ 27 ].…”