As research findings in general, results of this thesis certainly arise more questions than they are able to answer. The best I can hope is that some of these questions stand at more advanced level than those from which this thesis started. Table 2 lists some questions arising from the present findings.
Finding Questions
Recovery cycles of laser evoked responses
Could recovery of the pain system be distorted in some pain disorders?
C-nociceptor-mediated brain responses
Could laser-evoked responses reveal selective involvement of certain pain-mediating system in some pain disorders?
What is the role of the posterior parietal cortex in pain?
Modulation of the primary motor cortex function and corticomuscular coherence by painful stimulation
How are the pain-related suppression of oscillations and increase in coherence related to behavioral changes, such as changes in reaction time and speed of ongoing movement?
How does long-term noxious stimulation affect the spontaneous activity of the motor cortex?
Is the cortical motor system involved in tension-type pain?
Brain correlates of suggestion-induced pain
Could the activity of sensory pain processing circuitry differ between patients with pain of predominantly physical and psychological origin?
What are the brain mechanisms that mediate activation of the pain circuitry during suggestion-induced pain?
Brain correlates of subjective reality of pain
What is the role of the medial prefrontal cortex in the experience of reality?
Could similar systems be involved in psychotic disorders?
Table 2. Some questions arising from the findings of this thesis.
7 Conclusions
Whereas acute pain has an important protective function, chronic pain does not have physiological meaning. Knowledge about pain is needed especially to help those numerous people suffering from chronic pain. This thesis aimed to increase understanding about brain function related to acute pain, and to build thereby basis for studies on chronic pain. We found that both laser-evoked fields and potentials increase in amplitude with increasing ISI up to about 4 s and saturate thereafter.
Based on these findings, optimum signal-to-noise ratio in a fixed measurement time is achieved by inter-stimulus intervals of 4–5 s (Study I). Characterization of cortical responses to painful C-fiber stimuli revealed that the C-fiber-mediated pain activates similar cortical network than Aδ−mediated pain, including the bilateral somatosensory cortices and the posterior parietal cortex (Study II).
Selectively painful laser stimuli suppressed spontaneous oscillatory activity of the MI cortex (Study III) and, during isometric muscle contraction, increased oscillatory cortex–muscle coupling (Study IV).
Suggestion-induced and laser-induced pain were associated with similar activation of the emotional parts of the brains’s pain circuitry, whereas the laser-induced pain was related to stronger activations of sensory parts of this circuitry (Study V). Subjective reality of laser-induced pain correlated with activation strengths in the sensory pain-processing areas. During suggestion-induced pain, the subjective reality of pain correlated with activation strengths in the medial prefrontal cortex, and similar trend was evident during laser-induced pain.
Our findings help to apply cortical laser-evoked responses more effectively (Study I), and to address involvement of Aδ- vs. C-fiber system in chronic pain disorders (Study II). The findings of pain-related PPC (Study II) and MI (Studies III and IV) activation arise question about role of these regions in acute and chronic
pain. Results on brain correlates of suggestion-induced pain and subjective reality of pain (Study V) benefit understanding of psychological modulation of pain, and may be helpful for studies on mechanisms of reality distortions in psychiatric disorders.
Acknowledgments
Work for this thesis was conducted at the Brain Research Unit of the Low Temperature Laboratory (LTL) and at the Advanced Magnetic Imaging Centre of the Helsinki University of Technology, and it was financially supported by the Finnish Graduate School for Neuroscience, the Signe and Ane Gyllenberg foundation, and the Maud Kuistila foundation, and via LTL by the Academy of Finland.
It has been honor to work in such a high-quality unit as LTL is. I am thankful for this possibility to the founder of LTL, late Academician Olli V.
Lounasmaa, to current director of LTL, Professor Mikko Paalanen, and to the head of the Brain Research Unit, Professor Riitta Hari. I have had a privilege to conduct my graduate studies under supervision of Prof. Hari, whos enthusiasm and knowledge about human mind and brain I can’t stop admiring. To my other supervisor, Doc. Nina Forss, I owe greatest thanks for her skilful guidance, inspiring scientific discussions, and for her great impact on the atmosphere of LTL.
I want to thank Prof. Eija Kalso and Doc. Juha Huttunen for constructive suggestions on the manuscript of this thesis.
I am grateful to my co-authors Phil. Lic. Jaana Hiltunen, and Drs. Veikko Jousmäki, Jussi Numminen, Sakari Närvänen, Andrej Stancak, and Nuutti Vartiainen for collaboration.
Great thanks to the “AIVO social group” and the “graduate students’ floor ball team” for the great time spent together, and to Dr. Tommi Raij for his inspiring example.
I’m thankful to my parents, sister, brother, captains of the Venekerho, and all my friends for their support and relaxing company.
I owe my greatest thanks to Mr. Samuel Aulanko, Mrs. Mia Ilman, Dr. Ole Jensen, Dr. Raimo Joensuu, Mrs. Marita Kattelus, Dr. Hanna Renvall, Mr. Ville Renvall, Prof. Riitta Salmelin, Dr. Martin Schürmann, Mr. Mika Seppä, Dr.
Cristina Simões, Mr. Topi Tanskanen, and Dr. Antti Tarkiainen for their expert help and advice.
The great equipment and support provided by Neuromag Ltd. and General Electrics have been essential for my work. Thank you!
Great thanks to the computer support team—Samuli Hakala, Jan Kujala, Mika Seppä, Antti Tarkiainen, and Kimmo Uutela; without their help this thesis would have taken much longer time.
I would also like to thank Sari Avikainen, Peter Berglund, Gina Caetano, Katri Cornelissen, Nobuya Fujiki, Teija Halme, Päivi Helenius, Liisa Helle, Linda Henriksson, Kati Hirvonen, Yevhen Hlushchuk, Marja Holmström, Annika Hulden, Kaisa Hytönen, Marianne Inkinen, Antti Jalava, Helge Kainulainen, Erika Kirveskari, Tuire Koivisto, Hannu Laaksonen, Martin Lehécka, Sari Levänen, Mia Liljeström, Sasu Liuhanen, Sanna Malinen, Mika Martikainen, Seppo Mattila, Pirjo Muukkonen, Jyrki Mäkelä, Satu Pakarinen, Lauri Parkkonen, Tiina Parviainen, Liisi Pasanen, Marjatta Pohja, Antti Puurula, Miiamaaria Saarela, Timo Saarinen, Stephan Salenius, Ronny Schreiber, Teija Silén, Linda Stenbacka, Oguz Tanzer, Johanna Uusvuori, Simo Vanni, Minna Vihla, and all the other former and present members of LTL personnel; without them there would not be this Center of Excellence. I also wish to thank Flamine Alary, Ken-Ichi Kaneko, Marieke Longcamp, Takeshi Morita, Nobuyuki Nishitani and all the other visitors who have created lively international atmosphere in our laboratory. Special thanks to Juha Järveläinen for friendship and inspiring conversations.
I highly appreciate participation of the subjects in my painful studies.
Most of all I want to thank my wife Niina for her patience and support, my daughter Pinja for her energy and creativity, and my son Oiva for smiles in the mornings. This thesis I dedicate to them.
May 2005
Tuukka Raij
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