An Improved Method for Intrathecal Catheterization in the Rat / 한국실험동물학회지

Catheterization of the subarachnoid space provides a useful tool to deliver drugs to spinal cord in rat. However, the passage of a long intrathecal catheter inserted via the cisterna magnum to lumbar spinal levels increases the risk of spinal cord trauma and the mislocation of catether into other places. Thus, present study was aimed to introduce direct subarachnoid catheterization of the rat lumbar spinal cord with novel shape of catheter. An intrathecal PE-10 catheter was fabricated with coil (four-time helix with 2 mm diameter) on either end and attached small silicon beads on both end of the coil. Using the silicon bead at insertion part as an anchorage, the catheter was advanced into the subarachnoid space until the silicon bead was embedded on a drilled hole over interspinous space between L4 and L5 vertebra. And then, silicon bead was tightly attached by surgical glue and dental resin with vertebra. Using the other side of silicon bead, catheter was tightly suturing with muscle layer. Finally, external portion of the catheter was placed into stainless steel protector on neck to reduce the damage by rat. Following this catheterization, it is not significantly affect the general physiology (i.e. motor function, weight gain and mechanical allodynia) of the rat without catheter loss over 2 weeks. Moreover, intrathecal injection either fluorescent dye or lidocaine further confirmed that drug diffusion site was appropriated for intended target.

The Antinociceptive Effect of Sigma-1 Receptor Antagonist, BD1047, in a Capsaicin Induced Headache Model in Rats

Intracranial headaches, including migraines, are mediated by nociceptive activation of the trigeminal nucleus caudalis (TNC), but the precise mechanisms are poorly understood. We previously demonstrated that selective blockage of spinal sigma-1 receptors (Sig-1R) produces a prominent antinociceptive effect in several types of pain models. This study evaluates whether the Sig-1R antagonist (BD1047) has an antinociceptive effect on capsaicin (a potent C-fiber activator) induced headache models in rats. Intracisternal infusion of capsaicin evoked pain behavior (face grooming), which was significantly attenuated by BD1047 pretreatment. BD1047 consistently reduced capsaicin-induced Fos-like immunoreactivity (Fos-LI), a neuronal activator, in the TNC in a dose-dependent manner. Moreover, capsaicin-induced phosphorylation of N-methyl-D-aspartate receptor subunit 1 was reversed by BD1047 pretreatment in the TNC. These results indicate that the Sig-1R antagonist has an inhibitory effect on nociceptive activation of the TNC in the capsaicin-induced headache animal model.