The gap junction inhibitor INI-0602 attenuates mechanical allodynia and depression-like behaviors induced by spared nerve injury in rats
2019
: Gap junctions (GJs) are novel molecular targets for pain therapeutics due to their pain-promoting function. INI-0602, a new GJ inhibitor, exerts a neuroprotective role, while its role in neuropathic pain is unclear. The objective was to investigate the analgesic role and mechanisms of INI-0602 in neuropathic pain induced by spared nerve injury (SNI), and whether INI-0602 attenuated pain-induced depression-like behaviors. Rats were randomly assigned to saline treatment groups (sham+NS and SNI+NS) or INI-0602 treatment groups (sham+INI-0602 and SNI+INI-0602). The von Frey test was used to assess pain behavior, and the sucrose preference test, the forced swimming test, and the tail suspension test were used to assess depression-like behaviors. Gap junction intercellular communication (GJIC) was measured by parachute assay. Western blots were used to determine the protein expression. In vitro, INI-0602 significantly suppressed GJIC by decreasing connexin43 and connexin32 expression. In vivo, INI-0602 significantly suppressed mechanical allodynia during initiation (7 days after SNI) and the maintenance phase (21 days after SNI) and simultaneously attenuated accompanying depression-like behaviors. Furthermore, INI-0602 markedly suppressed the activation of astrocytes and microglia on days 7 and 21 by reducing GJIC. Finally, INI-0602 reversed the changes in the brain-derived neurotrophic factor and Nr2b subunits of the N-methyl-D-aspartate receptor in SNI rats, suggesting that these effects of INI-0602 were related to its analgesic effect. Our findings demonstrated that blocking GJs with INI-0602 attenuated mechanical pain hypersensitivity and related depression-like behaviors in SNI rats by reducing glial activation.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
29
References
7
Citations
NaN
KQI