Involvement of Spinal Neuroplastin 65 in Neuropathic Pain by GABAA Receptor α2 Subunit Regulation

This study investigates the role of neuroplastin 65 (NP65) in neuropathic pain (NP) by examining its relationship with the gamma aminobutyric acid A receptor α2 subunit (GABAAR-α2). The researchers hypothesized that NP65 is involved in the development of NP by regulating the levels of GABAAR-α2 in the spinal cord. The study found that the expression of NP65 is decreased in a rat model of neuropathic pain. Overexpression of NP65 through intrathecal injection of adeno-associated virus alleviated pain behavior and upregulated GABAAR-α2 levels. In vitro experiments further confirmed that NP65 affects GABAAR-α2 expression via the calcineurin-nuclear factor of activated T-cell 4 (CaN-NFATc4) signaling pathway. The researchers concluded that NP65 modulates the level of GABAAR-α2 through the CaN-NFATc4 signaling pathway, which may be an underlying mechanism for neuropathic pain. This suggests that targeting NP65 could be a potential therapeutic strategy for managing neuropathic pain.

• 1
  The expression level of NP65 protein and mRNA were significantly decreased in the CCI group compared to the control group, indicating a downregulation of NP65 in neuropathic pain conditions.
• 2
  Intrathecal injection of NP65 overexpressing AAV in CCI rats significantly alleviated pain behavior and upregulated levels of GABAAR-α2, suggesting a therapeutic effect of NP65 overexpression.
• 3
  NP65 regulates GABAAR-α2 levels through the CaN-NFATc4 signaling pathway, as evidenced by in vitro experiments where alterations in NP65 expression affected the expression of GABAAR-α2, CaN, and phosphorylated NFATc4, and the specific CaN inhibitor cyclosporine A (CsA) blocked these changes.