Philip A.M. Rogers MRCVS

AP and Neurology

AP and Fos-Neurons

He_L; Wang M; Gao M; Zhou J (1992) Expression of c-fos protein in serotonergic neurons of rat brainstem after EAP. AETRIJ Oct-Dec 17(4):243-248. Dept of Neurobiology, Shanghai Med Univ, PRC. The c-fos proto-oncogene encodes a nuclear phosphoprotein, Fos which has been proposed to be a "third messenger" coupling short term extracellular signals to long term alteration in cell function. Using double labelling immunocytochemistry, the present work showed the co-localization of Fos protein and serotonin in the nucleus raphe dorsalis, nucleus raphe centralis superior and rostral ventromedial medulla. The possible relation of Fos protein to the biosynthesis of serotonin, awaits further investigation.

Ji_RR; Wang XM; Han JS (1992) Induction of Fos-like protein in the rat spinal cord after EAP stimulation. Sheng-Li-Hsueh-Pao Aug 44(4):394-400. Dept of Physiology, Beijing Med Univ, PRC. The expression of the c-fos proto-oncogene has been regarded as a marker for noxious stimulation. We now report that EAP stimulation (100 Hz, 0.3 ms, 1-2-3 mA, 30 min) at SP06 also induced c-fos expression in the rat spinal cord, as shown immunohistochemically by using antibody against the c-fos protein product Fos. In rats receiving EAP, many cells with Fos-like immunoreactivity (FLI) were observed in both dorsal and ventral horn of the spinal cord with dense labelling in laminae III and IV of the ipsilateral side. Only scattered FLI cells were found in laminae I and II. In contrast, FLI evoked by noxious stimulation (5% formalin injected sc at the hindfoot) occurred mainly in laminae I and II, rather than in III and IV. The c-fos expression was very low in control animals receiving neither formalin nor EAP. The site specificity of the c-fos expression induced by EAP is different from that evoked by noxious stimulation. The possibility that EAP-induced Fos protein might participate in AP-analgesia is currently under investigation.

Lee_JH; Beitz AJ (1993) The distribution of brain-stem and spinal cord nuclei associated with different frequencies of EAP-analgesia. Pain Jan 52(1):11-28. Dept of Vet Biology, Univ of Minnesota, St. Paul 55108. Immunocytochemical localization of the c-fos primary gene protein, Fos, was used to identify spinal cord and brain-stem sites activated by either 4-Hz or 100-Hz EAP applied to the ST36 points of both hind limbs in lightly anaesthetized Sprague-Dawley rats. The number and distribution of Fos-immunoreactive neurons in the brain stem and spinal cord of 4-Hz and 100-Hz EAP-treated rats were compared with these in anaesthesia and room control rats. Compared to non-stimulated control rats or rats in which EAP was applied to a non-AP point, both 4-Hz and 100-Hz EAP-treated groups exhibited a significantly more Fos-labelled neurons in the dorsal horn of the L2 spinal cord segment, lateral parabrachial nucleus, substantia nigra, nucleus raphe pallidus, dorsal raphe, locus coeruleus, posterior pretectal nucleus, and the lateroventral PAG. In the 4-Hz-treated group, significant increases in Fos labelling were also observed in the cuneiform nucleus, dorsal and laterodorsal subdivisions of the PAG, habenular nucleus, arcuate hypothalamic nucleus, and the lateroventral and lateral hypothalamic nuclei as compared to non-stimulated controls. The only brain-stem nucleus that exhibited significantly increased Fos-immunoreactive neurons in 100-Hz but not 4-Hz EAP was the rostolateroventral nucleus of the medulla. Many brain-stem regions are activated by both 4-Hz and 100-Hz EAP but additional brain-stem regions are selectively activated by 4-Hz EAP which may relate to the opiate sensitivity of 4-Hz EAP. The data identify several distinct brain-stem nuclei that may play a role in AP-analgesia.

Ma_QP2; Zhou Y; Han JS (1993) EAP accelerated the expression of c-Fos protooncogene in dopaminergic neurons in the ventral tegmental area of the rat. Int J Neurosci Jun 70(3-4):217-222. Dept of Physiology, Beijing Med Univ, PRC. The mesolimbic dopaminergic system has been implicated in mediating morphine and EAP-analgesia. In the present study, Fos immunoreactivity was used as a marker of neuronal activity to study if EAP could activate the dopaminergic neurons in the midbrain. EAP significantly increased the number of Fos-positive dopaminergic neurons in the ventral tegmental area (VTA), whereas no significant c-fos expression in the dopaminergic neurons was observed in the substantia nigra (SN). VTA rather than the SN may play a role in mediating EAP-analgesia.

Pan_B; Castro Lopes JM; Coimbra A (1994) C-fos expression in the hypothalamo-pituitary system induced by EAP or noxious stimulation. Neuroreport 15 Aug 5(13):1649-1652. Inst of Histology and Embryology, Fac of Med, Univ of Oporto, Porto, Portugal. In the anaesthetized rat, low frequency electrostimulation of ST36 or noxious thermal stimulation caused by immersing the footpad in water at 52oC caused marked expression of c-fos in the anterior lobe of the pituitary gland, as well as in the arcuate and some nearby hypothalamic nuclei. A similar anterior lobe response was caused by immobilization stress in awake rats but in this case Fos-immunoreactive cells extended into the intermediate lobe and were very abundant in the paraventricular nucleus. The anterior pituitary cells that respond to stress are also activated by AP or painful stimuli. However, mechanisms of activation of pituitary cells by AP are distinct from those activated by stress, as different hypothalamic nuclei are involved.