Activation of the c-fos Proto-Oncogene in the Spinal Cord Following Noxious Stimulation of the Urinary Bladder

Abstract

Activation of the c-fos proto-oncogene following mechanical or chemical noxious stimulation of the urinary bladder was studied at T₁₂-L₂ and L₅-S₁, the spinal cord segments of projection of the hypogastric nerve (HGN) and pelvic nerve (PN) fibers, respectively. In intact adult rats, c-fos expression was found at T₁₂-L₂ only in lamina I. At L₅-S₁, Fos cells occurred in lamina I, the intermediolateral gray matter (ILG), and the dorsal commissure (DCM). These two areas contained the highest number of immunoreactive cells. Although more Fos cells were induced by mechanical than by chemical stimulation, the distribution of the reactive neurons was similar after both types of stimuli. In adult rats that had been treated neonatally with capsaicin, there was a marked fall in c-fos activation by mechanical or chemical noxious stimuli in all immunoreactive areas. The loss of Fos cells was more pronounced in ILG and DCM at L₅-S₁ (95%) than in lamina I at the two spinal domains (70%). The confinement of c-fos activation to lamina I at T₁₂-L₂, the spinal cord domain of the HGN, suggests that the input carried from the bladder by this nerve is preferentially used for pain perception. The same function is expected for noxious input reaching lamina I at L₅-S₁, the spinal cord territory of termination of the PN. However, the striking number of Fos cells in ILG and DCM supports the important role played by this nerve in the control of the micturition reflex. The marked block of c-fos activation in ILG and DCM by capsaicin suggests, in addition, that these bladder reflexogenic areas receive massive sensory input through unmyelinated C fibers.

Key Words:

• c-fos
• nociception
• hypogastric nerve
• pelvic nerve
• spinal cord
• bladder
• capsaicin
• rat