The role of galanin in chronic pain mechanisms

Abstract: The general aim of these studies is to further elucidate the role of galanin in pain mechanisms. We have utilized normal and genetically modified animals and a variety of techniques. In order to use genetically modified mice to study chronic pain, we adapted a photochemically-induced, peripheral nerve ischemia model, originally developed in rats, to mice. Both morphological and behavioral studies were conducted to determine the optimal irradiation time for producing hypersensitivity after partial nerve injury. This model was then used to study galanin over-expressing mice and mice lacking the galanin receptor 1. The normal basal response of these mice to sensory testing was also determined. During basal conditions, the over-expressing mice showed less sensitivity to thermal stimulation than the normal controls. After the photochemically-induced peripheral nerve ischemia, the over- expressing mice showed reduced development of heat and mechanical hyperalgesia as compared to wild-type mice. In contrast, the mice lacking the galanin receptor 1 displayed hypersensitivity to cold and heat in the hot-plate test under basal condition. After photochemically-induced nerve injury these mice exhibited a longer lasting hypersensitivity than wild-type controls, and this was not due to a slower nerve regeneration. A microdialysis technique to measure the release of galanin in the dorsal horn of the spinal cord in rat was developed. Using this method it could be demonstrated that electrical stimulation of primary afferent C-fibers causes release of galanin in the dorsal horn. of normal rats. The data presented in this thesis suggest that galanin primarily plays an inhibitory role in nociception under basal conditions. This role is further strengthened after peripheral nerve ischemia, where endogenous galanin appears to reduce the severity and duration of pain-like behaviors via activation of galanin receptor 1.