Reduced substance P-like immunoreactivity in hereditary sensory neuropathy of pointer dogs

Two unrelated Pointer dogs, each from a breeding of normal parents which produced three affected pups in a litter of nine, began to bite their paws at 3 and 5 months of age. Insensitivity to painful stimuli was marked in the distal parts of the limbs and receded proximally. The affected dogs were euthanatized at 5 and 20 months because of acral mutilation and infection. Changes affecting the primary sensory neurons included: small spinal ganglia with reduced numbers of cell bodies, degeneration of unmyelinated and myelinated fibers in dorsal roots and peripheral nerves, and reduced fiber density in the dorsolateral fasciculus (dlf). Since nociceptive loss was the salient deficit in a neuropathy affecting primary sensory neurons, immunohistochemical studies focused on substance P, the undecapeptide imputed to mediate nociception at the first synapse in the spinal cord and brain. The localization and density of substance P-like (SPL) immunoreactivity was studied in three control dogs and the two Pointers by the indirect antibody peroxidase-antiperoxidase method. The spinal intumescences of the control dogs contained dense SPL-immunoreactivity in fibers of the dlf and the superficial laminae of the dorsal horn (i.e., laminae I, II, and the dorsal part of III). Immunoreactive fascicles on the lateral aspect of the dorsal horn and in the reticular process sent contributions medially to a plexiform fiber arrangement in lamina V. Medially, SPL-immunoreactive fibers were more loosely arranged in the internal third of laminae VI and VII and in lamina X.(ABSTRACT TRUNCATED AT 250 WORDS)