THALAMIC LESION EFFECTS ON AVERSIVE BEHAVIORS

这项研究的总体目标是增强我们对如何

The overall goal of this research is to enhance our understanding of how the aversive quality of pain is represented in the brain. Clinicians would welcome better methods for selectively reducing the unpleasantness of pain, while preserving other aspects of the sensation. Clinical, anatomical and physiological evidence speaks for a role of the thalamus in the conscious appreciation of pain. Nociceptive input is distributed to a variety of telencephalic targets from a number of thalamic nuclei, which represent nodes in a complex network of sensory, motor and limbic interactions. This research will provide a better insight into the function if diencephalic nociceptive systems and thus will aid in the development of treatments for presently intractable pain conditions. This proposal focuses on three diencephalic regions for which existing knowledge suggests a role in affective aspects of pain and/or related behaviors: the zona incerta, the nucleus submedius and the center median/parafascicular complex. The general approach is to measure the effect of bilateral stereotaxic radiofrequency lesions on operant behaviors elicited by nociceptive (heat) and non-nociceptive (bright light) aversive stimuli in the rat, in order to discriminate between different potential consequences of these lesions. The proposed behavioral assays are using different stimuli to elicit the same motor behavior, in order to differentiate between specific effects on nociception, generalized effects on aversion and motor effects. The tests further allow comparisons between effects on consciously perceived pain sensations (inferred from consciously directed learned escape behaviors) and more primitive, possible reflexive responses, such as hindpaw-licking. Proposed methodological refinements in the stereotaxic lesioning technique are expected to limit the extent of thalamic damage: 1.) corrections of stereotaxic errors due to inter-subject variability are made after surveying skeletal landmarks; 2.) the radiofrequency lesions are temperature-feedback controlled for achieving a predictable lesion size. Better focused and reproducible lesions facilitate greatly the interpretation of the resulting behavioral deficits.