Summary
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-immuno-reactivity 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. In the Pointers, the loss of primary sensory neurons was associated with notable reduction of SPL staining in the dlf and superficial laminae of the dorsal horn. In the lumbar intumescence of the older Pointer greater preservation of SPL staining in the lateral third of laminae I and II was consistent with somatotopic termination of trunkal afferents in this region.
In both Pointers there was no detectable decrease in trigeminal sensitivity and the SPL immunoreactivity in the spinal nucleus of the trigeminal nerve of the younger Pointer and the corresponding control dog appeared equivalent. In the older Pointer, however, the immunoreactivity in this nucleus was decreased relative to the control. This decrease and appearance of scattered fiber degeneration in the dorsal columns of the mature Pointer suggested that fiber degeneration progresses slowly with age to include sensory systems not affected in early postnatal life.
The findings in the Pointers were compared with those made in immunohistochemical studies of SP in familial dysautonomia and the mutilated foot rat.
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Cummings, J.F., de Lahunta, A., Simpson, S.T. et al. Reduced substance P-like immunoreactivity in hereditary sensory neuropathy of Pointer dogs. Acta Neuropathol 63, 33–40 (1984). https://doi.org/10.1007/BF00688468
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DOI: https://doi.org/10.1007/BF00688468