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

To understand how the brain and spinal cord processes nociceptive information and how this processing changes during long term nociceptive input, valid animal models of pain are needed. The main aim of the present thesis was to develop a translational animal model based on cortical recordings for assessing pain related mechanisms. To this end, focus was put on evaluating changes in nociceptive transmission to the primary somatosensory cortex (SI). A comparison with changes in nocifensive responses, commonly used to assess pain related mechanisms, was also made.

It is demonstrated that both a sedative and an analgesic compound can inhibit CO2 laser C fibre evoked potentials (LCEPs) in SI and that by adjusting for effects on the electroencephalogram, sedative effects can be differentiated from the analgesic effects in anaesthetized rats.

Following induction of hyperalgesia with UVB-light, LCEPs from both the primary and the secondary hyperalgesic skin was significantly increased in awake animals. In anaesthetised animal, LCEPs increased from secondary hyperalgesic skin. The opiate tramadol counteracted the UVB induced changes. From recordings in awake animals using implanted multichannel electrodes this hyperalgesia was found to peak the first day and then decline over 2-14 days. Nocifensive responses increased from the primary hyperalgesic skin and occurred later than the changes of LCEP, indicating that pathways to motor circuits and sensory circuits differ substantially. These findings suggests that multichannel electrodes implanted in rat SI offer a more valid test for hyperalgesia in rats than conventional models based on behavioural measurements.