Introduction: Nucleus reticularis paragigantocellularis (PGi) is one of the major components of the rostral ventromedial medulla (RVM), which is involved in nociceptive processing and pain modulation. The aim of this study was to examine the effect of C fiber destruction on responsiveness of nucleus reticularis paragigantocellularis (PGi) to formalin, as a noxious stimulus, in normal and morphine dependent rats. Material and Methods: C-fiber destruction was induced by neonatal capsaicin (CAP) treatment (50mg/Kg, s.c.), in the second postnatal day. Extracellular single unit recording was used in control, capsaicin treated and morphine dependent, urethane (1.2-1.5g/Kg) anesthetized rats. After baseline recording (40 min), 100µl formalin (5%) was injected into the controlateral hind paw and recording was continued in the PGi, for 60 min after noxious stimulus. Results: In control rats three types of neurons were detected, which were categorized as, increased (38.45%), decreased (23.1%) and neutral neurons (38.45%). In CAP treated rats the 3 types of neurons were observed, too. The duration of response (Baseline ± 2SD), in CAP treated rats was significantly shorter than that of controls. All recorded neurons in morphine dependent rats were neutral, but 30% of recorded neurons in CAP treated morphine dependent rats showed short increase in firing rate. Conclusion: It was concluded that C-fiber destruction may just reduce the time course of changes in firing rate in response to peripheral noxious stimulus, while chronic morphine exposure may suppress the neuronal responsiveness, totally.