Involvement of EphB1 receptors signalling in models of inflammatory and neuropathic pain.

EphB receptors tyrosine kinases and ephrinB ligands were first identified as guidance molecules involved in the establishment of topographical mapping and connectivity in the nervous system during development. Later in development and into adulthood their primary role would switch from guidance to activity-dependent modulation of synaptic efficacy. In sensory systems, they play a role in both the onset of inflammatory and neuropathic pain, and in the establishment of central sensitisation, an NMDA-mediated form of synaptic plasticity thought to underlie most forms of chronic pain.

Nociceptor-expressed ephrin-B2 regulates inflammatory and neuropathic pain.

Background: EphB receptors and their ephrin-B ligands play an important role in nervous system development, as well as synapse formation and plasticity in the adult brain. Recent studies show that intrathecal treatment with EphB-receptor activator ephrinB2-Fc induced thermal hyperalgesia and mechanical allodynia in rat, indicating that ephrin-B2 in small dorsal root ganglia (DRG) neurons and EphB receptors in the spinal cord modulate pain processing. To examine the role of ephrin-B2 in peripheral pain pathways, we deleted ephrin-B2 in Nav1.

Tamoxifen-inducible NaV1.8-CreERT2 recombinase activity in nociceptive neurons of dorsal root ganglia.

To explore the function of genes expressed in adult mouse nociceptive neurons, we generated heterozygous knock-in mice expressing the tamoxifen-inducible Cre recombinase construct CreERT2 downstream of the Na(V)1.8 promoter. CreERT2 encodes a Cre recombinase (Cre) fused to a mutant estrogen ligand-binding domain (ERT2) that requires the presence of tamoxifen for activity.

BDNF modulates sensory neuron synaptic activity by a facilitation of GABA transmission in the dorsal horn.

Topical application of brain-derived neurotrophic factor (BDNF) to the adult rat isolated dorsal horn with dorsal root attached preparation inhibited the electrically evoked release of substance P (SP) from sensory neurons. This effect of BDNF was dose dependent (EC(50) 250 pM) and reversed by the tyrosine kinase inhibitor, K-252a. BDNF-induced inhibition of SP release was blocked by the GABA(B) receptor antagonist CGP 55485 but not by naloxone.

A peripheral nervous system actin-binding protein regulates neurite outgrowth.

Difference cloning has identified a Villin-like mRNA transcript expressed selectively in peripheral sensory and sympathetic neurons. Pervin, the encoded 820-amino acid protein, has 60% identity with Villin and is the rat homologue of Advillin. Coimmunoprecipitation studies demonstrate that Pervin and actin interact in vivo.