1. Paincognition and suffering Aya Nakae Osaka University Graduate School of Medicine, Department of Anesthesiology

2. Outline  What is pain?  My research What is “schizophrenia?” The correlation between schizophrenia and chronic pain Results  Future plans

3. The definition of pain Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.

4. What is pain? (Simple cases) 1. Tissue damage occurs. 2. Inflammation change occurs. 3. As a result, patients feel pain. 4. Pain disappears with the scar.

5. What is pain? (Difficult cases)  Some patients feel pain for a long time.  Many such patients feel more pain than predicted by tests.  Patients are unable to work.

6. Components of pain Pain behaviours Suffering Perception of Pain Nociception 1.Nociception 2.Perception of Pain 3.Suffering 4.Pain behaviours

7. Nociception

8. Perception of pain  The message is received by the brain and pain is perceived because of the way, the brain works in individuals. Perception of Pain

9. Suffering Negative and emotional reactions caused by  pain  depression  fear  anxiety  stress  etc Suffering

10. Pain behaviours  Saying” Ouch!!”  Grimacing  Limping  Lying down  Recourse to health care  Refusing work Pain behaviours

11. The purpose of our research The clarification of the process from pain perception to suffering through researching patients with schizophrenia and chronic pain.

12. Why patients with schizophrenia? They are less sensitive to pain  ruptured appendix  perforated bowels  peritonitis  painless myocardial infarction  Chronic pain is rare. ? ? ?

13. Why are they less sensitive?  Cognitive impairment  Affective impairment  Attention deficiency

14. Why patients with schizophrenia? Pain Suffering Pain Behaviour Patients with chronic painPatients with schizophrenia

15. Degree of pain suffering Strong Weak Schizophrenia Normal Chronic pain Schizophrenia is a human model considered to be the opposite of that with chronic pain.

16. Methods Chieko Takamura Chieko was an artist who created many works of art after suffering with schizophrenia.

17. Participants  Patients with schizophrenia: - Diagnosed using DSM-IV criteria - Exclusion criteria 1) cannot understand the test 2) cannot answer the questionnaire accurately  Healthy control: - Not diagnosed with any psychiatric illnesses

18. Clinical assessments of patients  Symptoms of schizophrenia - Positive and Negative Syndrome Scale (PANSS)  Medication - Chlorpromazine equivalents  History  patient’s age on diagnosis  diabetes  self injury  etc.

19. Pain assessments  Electrical stimulation - minimum detection threshold - pain detection threshold - pain tolerance  Thermal stimulation - warm/cold detection threshold - heat/cold pain threshold - heat/cold tolerance

20. Expression of pain  McGill Pain Questionnaire (short form) S-PRI: Subjective assessments A-PRI: Affective assessments T-PRI: Total assessments  Visual Analogue Scale (VAS)

21. Results This picture by Norwegian artist Edvard Munch is said to show the hallucination of a patient with schizophrenia.

22. Participants PatientsControls Total3932 Male15 Female2417 Age Patients (Mean  SEM) Controls (Mean  SEM) Total37.2 (±12.9)35.7 (±9.8) Male37.3 (±14.9)36.3 (±9.1) Female37.2 (±12.2)35.1 (±10.7)

23. Discussion Self-portrait with bandaged ear. Vincent van Gogh, who was troubled By mental health, cut off his own ear.

24. Causes of Schizophrenia  Genetic Intermediate phenotypes  Prenatal  Social  Others Eugen Bleuler (1857-1939) coined the term "Schizophrenia" in 1908.

25. What is a phenotype? Gregor Johann Mendel

26. The phenotype Patients Control The data showed potential phenotype groups in schizophrenia.

27. Analgesic effect of antipsychotics? Dopamine D2 antagonist (traditional Antipsychotics) and opioids Neuroleptic analgesia Less sensitivity to pain due to antipsychotics’ analgesic effects? Not dosage dependent

28. Severe schizophrenia?  Less sensitivity to pain due to the symptoms of schizophrenia? No correlation between symptoms and pain sensitivity No correlation between symptoms and pain sensitivity shown in PANSS (schizophrenia syndrome scale) data.

29. Schizophrenia Normal HPT and pain suffering Strong Weak Schizophrenia Normal Chronic pain Degree of pain suffering Heat pain threshold High Low Patients with normal heat pain thresholds have a normal degree of suffering? ?

30. Patient 1: Confident against pain!!  History of spinal contusion injury(SCI)  No pain  No analgesics HighLow Heat pain threshold

31. Patient 2: Always feels knee pain  Feels pain due to osteoarthritis in the knee.  Receives general therapy for knee pain HighLow Heat pain threshold

32. Patient 3: Feels pain but ・・・・ ・  History of SCI with paralysis  She feel pain.  She looks free from pain HighLow Heat pain threshold

33. Schizophrenia Normal HPT and pain suffering Strong Weak Schizophrenia Normal Chronic pain Degree of pain suffering Heat pain threshold High Low

34. Why don’t need analgesics?  The last patient felt pain.  She didn’t want her pain treated. Pain is an unpleasant sensory and emotional experience  Her pain probably was not so unpleasant to require treatment.

35. Schizophrenia less sensitive to pain 1. Sensory insensitivity 2. Less suffering due to the noxious stimuli ? ?? ? ?

36. Future plans (1, 2, 3 ・・・・ ) John Forbes Nash, Jr. is an American mathematician who received a Novel Prize for his works in game theory. Nash is the subject of the Hollywood movie “A Beautiful Mind”. The film focuses on Nash's mathematical genius and his struggle with schizophrenia.

37. 1. Detailed evaluation of sensitivity

38. 2. fMRI study  Participants Patients with schizophrenia not suffering from pain and Controls  Pain task 15˚C, 45˚C, 50˚C stimulation lasting 20s  Analyzing the areas which contribute to suffering

39. 3. Other possible imaging studies  Dopamine  Glutamate

40. Significance : Area detection Area detection Evaluation of degree and treatment Molecular mechanism Direct stimulation therapy

41. Significance : Genes Target gene Molecular mechanism New analgesic and anesthetic Progress in schizophrenia research

42. Acknowledgements Department of Psychiatry Ryota Hashimoto and his colleagues Nihon Koden Cooporation Syogo Maeda & Tomoko Oku Department of Pain Medicine Masahiko Shibata Graduate School of Dentistry Syoichi Ishigaki Department of Anesthesiology All my colleagues