Brain processing of experimental muscle pain and its interrelation with proprioception and muscle fatigue : positron emission tomography study

Abstract: Chronic muscle pain is a significant medical and social problem and better understanding of the pathophysiological mechanisms involved is an important requirernent for further development of diagnostics, treatment and rehabilitation methods. Experimental imaging studies have investigated functional neuroanatomy of different pain cornponents. However, several aspects ofbrain mechanisrns underlying brain processing ofmuscle pain rernain unclear.The general goal of the present thesis was to study functional brain anatomy of systerns underlying perception ofmuscle pain, processing ofproprioceptive information and maintenance of fatiguing muscle contractions with an ernphasize on their possible interrelations.Four series of experiment were carried out. Using an injection of hypertonic saline (HS) into the m. triceps to induce pain comparable with clinical muscle pain a significant activation of in sula and putamen as weIl as decrease of activit y in the temporal and occipital cortex in comparison with control stimulation were revealed. An advanced model of prolonged muscle pain were provided by the infusion of the HS during 20 minutes into m. erector spinae A cornplex dynamics of brain activit y during the habituation to nociceptive stimulation was shown: initial activation of insula changed to decrease of activit y in this and several other cortical areas. A conjunction analysis identified activations jointly significant in both experiments (despite localization of HS nociceptive stimulation) in the right insula, occipital and left parietal cortical areas. The study of brain activit y in response to different modalities of prorioceptive inputs - passive movernents, kinesthetic illusions and muscle vibration showed corresponding different patteros of activation in motor and sornatosenory areas and temporal areas. Finally, the study of sustained isometric muscle contractions of various force levels and durations revealed that muscle fatigue is associated with contralateral activation of the motor and sornatosensory areas and temporal areas and bilateral activation in the supplementary motor areas and cingular cortex, indicating that increased efforts needed to maintain required force and its eventual breakdown with fatigue might induce activation of additional cortical areas. Analysis of data obtained in all experimental series revealed that insula, secondary sornatosensory and auditory areas are activated during both perception of muscle pain and processing of somatosensory afferentation.In conclusion, this thesis has elucidated brain processing of muscle pain showing distributed, bilateral patteros cornprised of activated structures predominantly attributed to the medial pain system and deactivated structures. Furthermore, initial and late phases of tonic muscle pain are associated with different brain reactions, namely initial activation of the insula followed by a significant bilateral decrease of activit y at the late stage. Area of brain cortex located near lateral sulcus and cornprised of secondary sornatosensory cortex, posterior part of the insula and adjacent auditory cortex is engaged in the perception of muscle pain and processing of sornatosensory afferentation as weIl as rnaintenance of fatiguing muscle contractions.