{Reference Type}: Journal Article
{Title}: Pain hypersensitivity is dependent on autophagy protein Beclin 1 in males but not females.
{Author}: Tam TH;Zhang W;Tu Y;Hicks JL;Farcas S;Kim D;Salter MW;
{Journal}: Cell Rep
{Volume}: 43
{Issue}: 6
{Year}: 2024 Jun 25
暂无{DOI}: 10.1016/j.celrep.2024.114293
{Abstract}: Chronic pain is associated with alterations in fundamental cellular processes. Here, we investigate whether Beclin 1, a protein essential for initiating the cellular process of autophagy, is involved in pain processing and is targetable for pain relief. We find that monoallelic deletion of Becn1 increases inflammation-induced mechanical hypersensitivity in male mice. However, in females, loss of Becn1 does not affect inflammation-induced mechanical hypersensitivity. In males, intrathecal delivery of a Beclin 1 activator, tat-beclin 1, reverses inflammation- and nerve injury-induced mechanical hypersensitivity and prevents mechanical hypersensitivity induced by brain-derived neurotrophic factor (BDNF), a mediator of inflammatory and neuropathic pain. Pain signaling pathways converge on the enhancement of N-methyl-D-aspartate receptors (NMDARs) in spinal dorsal horn neurons. The loss of Becn1 upregulates synaptic NMDAR-mediated currents in dorsal horn neurons from males but not females. We conclude that inhibition of Beclin 1 in the dorsal horn is critical in mediating inflammatory and neuropathic pain signaling pathways in males.