Unraveling the central processing of pain by studying brain activity and behaviour in rats

Abstract

Pain is described as a subjective unpleasant sensory and emotional experience, which is generated in the brain. In both humans and animals, pain is frequently undertreated. The primary barrier to an effective pain treatment is the incomplete knowledge about underlying central mechanisms. In animals, the recognition and effective treatment of pain is furthermore hampered by a lack of reliable and quantifiable read-out parameters of pain. This necessitates the generation of more fundamental knowledge about animal pain (patho)physiology. When investigating and treating pain, it is important to acknowledge and address the multidimensional character of pain, i.e. affirm the relevance of both the sensory and emotional component. The sensory component relates to the recognition and determination of the type of stimulus, location, intensity, temporal pattern and duration of the pain experience. The emotional component relates to the affective-motivational aspect (e.g. pain unpleasantness). It is the latter component which determines the 'painfulness' or 'hurtfulness' in the subject’s experience. One promising tool to investigate pain is the somatosensory-evoked potential (SEP), which potentially quantifies and differentiates between the sensory and emotional component. SEPs are used in humans and animals to study the central processing of pain. Previous research, using anaesthetic interventions, supports the SEP as a valid method to objectively quantify central pain processing in animals. The studies described in this thesis focus on refinement of the technique to measure the SEP in rats and the subsequent validation of the SEP as a method to study central pain processing. The principal conclusion of the studies described in this thesis is that the SEP as such is to be considered a highly suitable tool to assess alterations in central pain processing caused by non-pharmacological interventions. Effects of an altered emotional state and differences in innate pain sensitivity on central pain processing are reflected in the cortically-derived SEP, further supporting the SEP as a valid and valuable read-out parameter in pain research. However, to investigate and differentially determine the underlying mechanisms of the sensory and emotional component of pain, the SEP's measurement technology applied needs to be refined further. More detailed and differential knowledge about the underlying central mechanisms of pain will ultimately contribute to the adequate treatment of animal pain.