cGMP-dependent protein kinase in dorsal root ganglion: Relationship with nitric oxide synthase and nociceptive neurons

Abstract

Nitric oxide and cGMP influence plasticity of nociceptive processing in spinal cord. However, effectors for cGMP have not been identified in sensory pathways. We now demonstrate that cGMP-dependent protein kinase I (cGKI) occurs in the DRGs at levels comparable to that in cerebellum, the richest source of cGKI in the body. Immunohistochemical studies reveal that cGKI is concentrated in a subpopulation of small- and medium-diameter DRG neurons that partially overlap with substance P and calcitonin gene-related polypeptide containing cells. During development, cGKI expression throughout the embryo is essentially restricted to sensory neurons and to the spinal floor and roof plates. Neuronal nitric oxide synthase (nNOS) is coexpressed with cGKI in sensory neurons during embryonic development and after peripheral nerve axotomy. The primary target for cGKI in cerebellum, G- substrate, is not present in developing, mature, or regenerating sensory neurons, indicating that other proteins serve as effectors for cGKI in sensory processing. These data establish sensory neurons as a primary focus for cGMP actions during development and suggest a role for cGKI in plasticity of nociception.