Chronic pain including neuropathic pain increases risk of cognitive dysfunction. High-mobility group box 1 (HMGB1), a damage-associated molecular pattern, is involved in the development and maintenance of neuropathic pain and cognitive dysfunction. However, the relationship between HMGB1 and cognitive dysfunction in chronic pain state is unclear. The current study examined the effects of neutralizing antibody (nAb) against HMGB1 on cognitive dysfunction and related changes of neuronal morphology in mice with neuropathic pain.
Neuropathic pain was induced by partial sciatic nerve ligation (PSNL) of male ddY mice. Cognitive function was evaluated by novel object recognition test. Neuronal morphology in the hippocampus was assessed using Golgi-Cox staining. Anti-HMGB1 nAb was intranasally administered to mice to deliver into brain.
Nerve injury significantly evoked mechanical hypersensitivity and cognitive dysfunction compared with sham group. Repeated administration of anti-HMGB1 nAb to mice with neuropathic pain improved maladaptive neuroplastic changes, such as decreases of dendritic length and spine density, in the hippocampus and cognitive dysfunction.
The current study suggests that HMGB1-mediated maladaptive neuroplastic changes in the hippocampus could be involved in cognitive dysfunction under neuropathic pain state.