Rab11a in the spinal cord: an essential contributor to complete Freund's adjuvant-induced inflammatory pain in mice

Mol Brain. 2023 Sep 28;16(1):70. doi: 10.1186/s13041-023-01057-3.

Abstract

Inflammatory pain is a commonly observed clinical symptom in a range of acute and chronic diseases. However, the mechanism of inflammatory pain is far from clear yet. Rab11a, a small molecule guanosine triphosphate enzyme, is reported to regulate orofacial inflammatory pain in our previous works. However, the mechanism of Rab11a's involvement in the regulation of inflammatory pain remains obscure. Here, we aim to elucidate the potential mechanisms through which Rab11a contributes to the development of inflammatory pain in the spinal level. It's shown that neurons, rather than glial cells, were the primary cell type expressing Rab11a in the spinal dorsal horn (SDH). After intra-plantar injection of CFA, both the number of Fos/Rab11a-immunopositive neurons and the expression of Rab11a were increased. Administration of Rab11a-shRNA into the SDH resulted in significantly analgesic effect in mice with CFA injection. Application of Rab11a-shRNA also reduced the NMDA receptor-mediated excitatory post-synaptic current (EPSC) and the spike number of neurons in lamina II of the SDH in mice with CFA injection, without affecting the presynaptic glutamate release and the postsynaptic AMPA receptor-mediated EPSC. Our results thus suggest that the enhanced expression of neuronal Rab11a may be important for the process of inflammatory pain in mice with CFA injection, which is likely mediated by Rab11a's potentiation of the competence of post-synaptic NMDAR and spiking of SDH neurons.

Keywords: Inflammatory pain; NMDA receptor; Rab11a; Spinal dorsal horn.

MeSH terms

  • Animals
  • Freund's Adjuvant
  • Hyperalgesia / metabolism
  • Inflammation / chemically induced
  • Mice
  • Neurons / metabolism
  • Pain* / complications
  • Pain* / metabolism
  • Posterior Horn Cells
  • RNA, Small Interfering / metabolism
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Spinal Cord Dorsal Horn / metabolism
  • Spinal Cord* / metabolism

Substances

  • Freund's Adjuvant
  • Receptors, N-Methyl-D-Aspartate
  • RNA, Small Interfering
  • rab11 protein