Figure 6. Immunohistochemical staining of DRG and spinal cord from human and canine subjects.

Dog and human sensory ganglia and spinal cord were harvested after intrathecal treatment with RTX, and immunohistochemical staining was performed. Trigeminal and DRG samples from dogs treated with RTX in an independently conducted GLP toxicology study were assessed by a pathologist. (A) At the maximum tolerated dose (3.6 μg/kg), 5 of 10 dogs treated with RTX showed mild pathology in the trigeminal, whereas 3 of 10 showed minimal pathology in the DRG after ICM injection (nonsignificant, Mantel-Haenszel χ²). (B) An example of an infrequent pathological manifestation is the formation of a neuronophagic nodule (arrows). (C) Dogs were injected in the cisterna magna. In the dog, a marked reduction in CGRP was observed in the cervical region of the dorsal spinal cord, with a near-total ablation of substance P (SP) staining at the same level (n = 5 dogs). **P ≤ 0.01. (D) One human patient was injected with RTX using an end-hole catheter positioned at the cauda equina. After RTX treatment, CGRP and SP staining was almost completely abolished in the lumbar spinal cord. Similar reductions were also observed in the thoracic spinal cord for CGRP and TRPV1. A single human was autopsied to procure tissue. To estimate the magnitude of the effect size, several sections of the single human sample (points shown in the graphs) were compared with untreated human sections.