Cognitive mechanisms in pain processing : Assessed with functional imaging methods

Abstract: The intensity and unpleasantness of a painful experience is often described as correlating well with the degree of noxious stimulation. However, the perception of pain is not a linear phenomenon, reflecting the signal from the peripheral neuron. Rather, the noxious input may be modulated at every level of the neural axis. Both low hierarchy brainstem processes and higher order cortical processes may change the pain perception. In this theses we have tried to describe some cognitive processes that are involved in such mechanisms. In the first study we show that the brainstem, including the hypothalamus, the PAG and the pons, is involved in the initial pain processing. This finding indicates the importance of an automatic immediate response to noxious input, possibly including various analgesic mechanisms. The second study shows that the primary somatosensory cortex (S1) co-varies pain specifically with other regions that are involved in pain processing. This finding indicates that pain is processed in a parallel and distributed fashion that is a pre-request for cognitive modulation processes. Also, because S1 was not activated during the subtraction analysis it is indicated that this region may be involved in pain processing although the net activity does not increase compared with the control stimulation. In the third study we show that the cognitive distraction decreases pain perception and the pain response in various structures processing pain. Also, the lateral orbitofrontal cortex is activated when the pain rating is decreased indicating an involvement in pain modulation. In the fourth study it is indicated that mechanisms involved in opioid analgesia also are present in placebo anlagesia, corroborating previous behavioral similarities between opioid and placebo analgesia. Especially, the rostral ACC, the lateral orbitofrontal cortex and the brainstem show functional similarities in these two analgesic states. In has previously been shown that amygdala activity is increased during fear processing, but decreased in pain processing - a finding that is contra-intuitive. In the fifth study we show that the ainygdala activity decreases when the subjects expect a more aversive painful experience and show more intense coping. We therefore suggest that decreased activity in arnygdala during pain may mirror cognitive coping strategies. Finally, in study six, it is shown that patients with touch evoked allodynia, also display decreased activity in the amygdala, which may suggest that these patients have developed coping strategies to deal with their pathological pain. Several other studies on chronic pain syndromes, have previously shown increased activity in the orbitofrontal cortex suggesting that modualtory functions may be involved in chronic pain. However, the studied group of patients with touch evoked allodynia did not show any such findings.