Alteration of the cell adhesion molecule L1 expression in a specific subset of primary afferent neurons contributes to neuropathic pain

Abstract

The cell adhesion molecule L1 (L1‐CAM) plays important functional roles in the developing and adult nervous systems. Here we show that peripheral nerve injury induced dynamic post‐transcriptional alteration of L1‐CAM in the rat dorsal root ganglia (DRGs) and spinal cord. Sciatic nerve transection (SCNT) changed the expression of L1‐CAM protein but not L1‐CAM mRNA. In DRGs, SCNT induced accumulation of the L1‐CAM into the surface of somata, which resulted in the formation of immunoreactive ring structures in a number of unmyelinated C‐fiber neurons. These neurons with L1‐CAM‐immunoreactive ring structures were heavily colocalized with phosphorylated p38 MAPK. Western blot analysis revealed the increase of full‐length L1‐CAM and decrease of fragments of L1‐CAM after SCNT in DRGs. Following SCNT, L1‐CAM‐immunoreactive profiles in the dorsal horn showed an increase mainly in pre‐synaptic areas of laminae I–II with a delayed onset and colocalized with growth‐associated protein 43. In contrast to DRGs, SCNT increased the proteolytic 80‐kDa fragment of L1‐CAM and decreased full‐length L1‐CAM in the spinal cord. The intrathecal injection of L1‐CAM antibody for the extracellular domain of L1‐CAM inhibited activation of p38 MAPK and emergence of ring structures of L1‐CAM immunoreactivity in injured DRG neurons. Moreover, inhibition of extracellular L1‐CAM binding by intrathecal administration of antibody suppressed the mechanical allodynia and thermal hyperalgesia induced by partial SCNT. Collectively, these data suggest that the modification of L1‐CAM in nociceptive pathways might be an important pathomechanism of neuropathic pain.