Gabapentin prevents synaptogenesis between sensory and spinal cord neurons induced by thrombospondin-4 acting on pre-synaptic Ca α δ subunits and involving T-type Ca channels.

Background And Purpose: Nerve injury induces concurrent up-regulation of the voltage-gated calcium channel subunit Ca α δ and the extracellular matrix protein thrombospondin-4 (TSP4) in dorsal root ganglia and dorsal spinal cord, leading to the development of a neuropathic pain state. Interactions of these proteins promote aberrant excitatory synaptogenesis that contributes to neuropathic pain state development through unknown mechanisms. We investigated the contributions of Ca α δ subunits and TSP4 to synaptogenesis, and the pathways involved in vitro, and whether treatment with gabapentin could block this process and pain development in vivo.

The Antinociceptive Properties of the Corydalis yanhusuo Extract.

Corydalis yanhusuo. W.T.

Central Mechanisms Mediating Thrombospondin-4-induced Pain States.

Peripheral nerve injury induces increased expression of thrombospondin-4 (TSP4) in spinal cord and dorsal root ganglia that contributes to neuropathic pain states through unknown mechanisms. Here, we test the hypothesis that TSP4 activates its receptor, the voltage-gated calcium channel Cavα2δ1 subunit (Cavα2δ1), on sensory afferent terminals in dorsal spinal cord to promote excitatory synaptogenesis and central sensitization that contribute to neuropathic pain states. We show that there is a direct molecular interaction between TSP4 and Cavα2δ1 in the spinal cord in vivo and that TSP4/Cavα2δ1-dependent processes lead to increased behavioral sensitivities to stimuli.

A novel analgesic isolated from a traditional Chinese medicine.

Background: Current pain management is limited, in particular, with regard to chronic pain. In an attempt to discover novel analgesics, we combined the approach developed to characterize traditional Chinese medicine (TCM), as part of the "herbalome" project, with the reverse pharmacology approach aimed at discovering new endogenous transmitters and hormones.

Results: In a plant used for centuries for its analgesic properties, we identify a compound, dehydrocorybulbine (DHCB), that is effective at alleviating thermally induced acute pain.