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Spotting pain in the brain. Towards a useful animal model of pain

By Tanja Jensen

Abstract

Current models of pain in conscious animals usually scores nocifensive responses. However, it is still unclear to what extent these responses are related to, for instance, the sensory discriminative or affective aspects of pain. This touches upon an intriguing question on how the nervous system processes nociceptive information in the conscious brain, a matter of which little is known. In order to illuminate how the nociception is processed, a suitable animal model for analysis on the conscious brain is essential. In this thesis, we pursued to develop an animal model to illuminate how nociception is processed in primary somatosensory cortex (SI), which is likely to play an important role in processing sensory aspects of pain. As part of this, differentiating the antinociceptive outcome of drugs would clarify confounding sedative properties of drugs when assessing analgetic effects. Surface electrodes or ultrathin implantable electrodes were used to record the transmission to SI. We show that both a sedative and an analgesic compound can inhibit nociceptive transmission to the cortex. Furthermore, by adjusting for effects on the electroencephalogram, CO2 laser C fibre evoked potentials (LCEP) may be used to distinguish between the sedative and analgesic effect of a drug in anaesthetized rats. To clarify the implications whether LCEP can provide information about central changes in anaesthetized and conscious rats, hyperalgesia was induced by partially irradiating the hind paw of rats with UVB-light. Changes were monitored during 14 days after induction of hyperalgesia in conscious animals, whereas changes from anaesthetised animals were collected one day after irradiation. A clear increase in LCEPs from both the primary and the secondary hyperalgesic skin, peaking the first day and declining over 14 days, was demonstrated. Also later onset latencies were observed the first day after exposure in awake rats. Additionally in anaesthetised rats, the LCEPs in forelimb SI elicited from forelimb skin displayed unaltered magnitude. This area was not monitored in conscious rats. Furthermore, tactile poke evoked potentials were also collected and displayed no change in anaesthetised rats, however, increased from secondary hyperalgesic skin day one in conscious rats. To further evaluate hyperalgesia in anaesthetised rats, tramadol was administered, which counteracted the changes induced by UVB exposure. This suggests that altered sensory processing related to hyperalgesia is reflected in altered LCEPs in SI. Comparing the time course and spatial characteristic of the changes in transmission to SI and the behavioural responses in the same animals, it is clear that there are prominent differences. Behavioural responses increased preferentially from the primary hyperalgesic skin. Moreover, the significant changes in nociceptive transmission to SI occurred earlier than those of motor responses. In view of this, it is conceivable that pathways to motor circuits and sensory circuits differ markedly. Together these findings show that multichannel electrodes implanted in SI may offer a more sensitive test for hyperalgesia in conscious, behaving rats than conventional models. The improvement of ground breaking neural interfaces has the potential to lay fundamentally new grounds for our understanding of how the nervous system processes nociceptive information in the long run

Topics: Basic Medicine, analgesics, freely moving rat, microelectrode, Nociception, Primary somatosensory cortex, Sedatives
Publisher: Division of Neuroscience, Department of Experimental Medical Sciences, Lund University
Year: 2011
OAI identifier: oai:lup.lub.lu.se:f1aa28c1-ad4e-4d6c-b671-33cfc2656e27
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