Frontal cingulotomy reconsidered from a WGA-HRP and c-Fos study in cat

A recent positron emission tomography (PET) study demonstrated that the anterior cingulate cortex (area 24), in addition to SI and SII cortices, was activated by painful stimuli. In order to elucidate the participation of relay nuclei in the ascending pain pathway to area 24, we performed a regrograde labelling study with WGA-HRP injection into area 24 in cats. Area 24 was found to receive pain-related thalamic inputs from the intralaminar nuclei including the central medial nucleus, midline nuclei, modiodorsal nucleus and possibly the submedial nucleus. We then examined the expression of Fos protein in CNS induced by formalin injection into the face in cats. Fos positive neurons were demonstrated in areas 23 and 24, the anterior limbic area, insular cortex, midline and paraventricular nuclei in the thalamus, paraventricular nucleus and other areas in the hypothalamus, and in many nuclei in the brainstem in both the formalin-injected group and the control group (anesthesia only). Labelled regions appeared to correspond to stress-related sites. The sole difference from the control group was the expression of Fos in the coronal gyrus and in the trigeminal caudalis nucleus in the experimental group. Although more Fos positive cells were observed in area 24 in experimental than in control cats, the difference was not significant. Our findings suggest that the demonstrated response of area 24 on PET scan represents stress- and emotion-related events rather than pain. Surgical intervention into the anterior cingulate cortex including cingulotomy thus appears to relieve stress and emotion associated with chronic pain, but not pain itself.