Comparison of the induction of c-fos-eGFP and Fos protein in the rat spinal cord and hypothalamus resulting from subcutaneous capsaicin or formalin injection

Abstract We evaluated whether a c- fos -enhanced green fluorescent protein (eGFP) transgenic rat line, which expresses the c- fos and eGFP fusion gene, can be useful for the study of nociceptive pathways and processing. Capsaicin solution (15%) or formalin (5%) was subcutaneously injected bilaterally into the hind paws (100 μL per each paw) of adult male c- fos -eGFP transgenic or wild-type rats. Control rats were injected with ethanol or physiological saline respectively. Transgenic and wild-type rats were perfused at 1.5, 3 and 6 h post injection, with some transgenic rats being perfused 24 h post injection. A comparison of eGFP in transgenic rats and Fos-like immunoreactivity (LI) in wild-type rats was made in the dorsal spinal cord, paraventricular nucleus (PVN) and supraoptic nucleus (SON). Oxytocin-LI (OXT-LI) was carried out to examine the activation of OXT neurons in the PVN and SON. Following capsaicin or formalin treatment, eGFP was maximally expressed at 6 h in the spinal cord and 3 h in the PVN and SON, whereas, Fos-LI was maximally expressed at 1.5 h in all the regions we analyzed. Induction of eGFP in the OXT neurons was observed after capsaicin or formalin treatment, while Fos-LI in the OXT neurons was observed only after formalin treatment. These results demonstrate that the peak induction of c- fos -eGFP following exposure to acute nociceptive stimuli was delayed by around 1.5–4.5 h, but more sensitive than endogenous Fos, suggesting that the c-fos -eGFP rat line can be useful for the study of nociceptive pathways and processing.