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.
