1. Ontology of Pain Barry Smith National Center for Ontological Research University at Buffalo

2. BFO A simple top-level ontology to support information integration in scientific research 2

3. Basic Formal Ontology Continuant Occurrent (Process, Event) Independent Continuant (thing, substance) Dependent Continuant http://ifomis.uni-saarland.de/bfo/ 3

4. Continuant Independent Continuant Dependent Continuant.......... Non-realizable Dependent Continuant (quality) Realizable Dependent Continuant (function, role, disposition) 4

5. Specifically dependent continuants Examples: the height (quality) of this patient the disposition of this patient to experience diarrhea 5

6. Continuant Independent Continuant Dependent Continuant.......... Non-realizable Dependent Continuant (quality) Realizable Dependent Continuant (function, disposition) 6

7. depends_on Continuant Occurrent process Independent Continuant thing Dependent Continuant quality................ temperature depends on bearer 7

8. realization depends_on realizable Continuant Occurrent Independent Continuant bearer Dependent Continuant disposition................ 8 Process of realization

9. universals, types, kinds Continuant Occurrent process, event Independent Continuant Dependent Continuant................ 9 particulars, instances

10. the particular case of redness (of this particular fly’s left eye) the universal red instantiates this instance of eye (in this particular fly) the universal eye instantiates depends_on 10

11. this particular case of redness red instantiates this eye (in this particular fly) eye instantiates depends on coloranatomical structure is_a 11

12. this particular eye (in this particular fly) the universal eye 12 instantiates at t 1

13. this particular eye (in this particular fly) the universal eye 13 instantiates at t 1 instantiates at t 2 instantiates at t 3

14. plant this plant 14 seedmature plant instantiates at t 1 instantiates at t 2 Phase transitions

15. portion of water this portion of H 2 0 15 portion of ice portion of liquid water portion of gas instantiates at t 1 instantiates at t 2 instantiates at t 3 Phase transitions

16. human John 16 embryofetusadultneonateinfantchild instantiates at t 1 instantiates at t 2 instantiates at t 3 instantiates at t 4 instantiates at t 5 instantiates at t 6 in nature, no sharp boundaries here

17. temperature John’s temperature 17 37ºC37.1ºC37.5ºC37.2ºC37.3ºC37.4ºC instantiates at t 1 instantiates at t 2 instantiates at t 3 instantiates at t 4 instantiates at t 5 instantiates at t 6 in nature, no sharp boundaries here

18. Dependent Continuants Dependent Continuant Quality, Pattern Realizable Dependent Continuant if the bearer ceases to exist, then its quality, function, role ceases to exist the color of my skin the function of my heart to pump blood my weight 18

19. Realizable dependent continuants Disposition: fragility, virulence, susceptibility, genetic disposition to disease X Function: to pump (of the heart), to unlock (of the key) 19

20. Disposition (Internally-Grounded Realizable Entity) disposition =def. a realizable entity which if it ceases to exist, then its bearer is physically changed, and whose realization occurs when this bearer is in some special physical circumstances, in virtue of the bearer’s physical make-up Axiom: every disposition has a physical bearer 20

21. Disposition Internally-Grounded Realizable Entity A disposition is a realizable entity which is such that, if it ceases to exist, then its bearer is physically changed, whose realization occurs, in virtue of the bearer’s physical make-up, when this bearer is in some special physical circumstances 21

22. OGMS Ontology for General Medical Science, http://code.google.com/p/ogms/ 22

23. Big Picture 23

24. Disorder an independent continuant fiat object part of the whole organism (boundaries hard to specify) 24

25. Where does Mount Everest begin and end? Cf. Barry Smith and David M. Mark, “Do Mountains Exist?”, Environment and Planning B, 30, 2003. 25

26. Disorder A fiat object part of an organism which serves as the bearer of a disposition of a certain sort This fiat object may have no determinate boundaries (compare: Downtown Santa Barbara) 26

27. A disease is a disposition having as its bearer a physical disorder in the organism and realized in pathological processes. etiological process produces disorder bears disposition realized_in pathological process produces abnormal bodily features recognized_as signs & symptomsinterpretive process produces diagnosis used_in 27

28. Influenza - infectious Etiological process - infection of airway epithelial cells with influenza virus produces Disorder - viable cells with influenza virus bears Disposition (disease) - flu realized_in Pathological process - acute inflammation produces Abnormal bodily features recognized_as Symptoms - weakness, dizziness Signs - fever Symptoms & Signs used_in Interpretive process produces Hypothesis - rule out influenza suggests Laboratory tests produces Test results - elevated serum antibody titers used_in Interpretive process produces Result - diagnosis that patient X has a disorder that bears the disease flu 28

29. 29

30. independent continuant dependent continuant disposition disease disorder John’s disordered heart John’s coronary heart disease occurrent process course of disease course of John’s disease 30

31. coronary heart disease John’s coronary heart disease 31 coronary disease at the stage of asymptomatic (‘silent’) infarction coronary disease at the stage of early lesions and small fibrous plaques coronary disease at the stage of stable angina coronary disease the stage of surface disruption of plaque coronary disease at the stage of unstable angina instantiates at t 1 instantiates at t 2 instantiates at t 3 instantiates at t 4 instantiates at t 5 time

32. OGMS:pathological process def. – A process in an organism that is clinically abnormal.* i) is not part of the life plan for an organism of the relevant type (unlike aging, pregnancy or menopause), ii) is causally linked to an elevated risk either of pain or other feelings of illness, or of death or dysfunction, and iii) is such that the elevated risk exceeds a certain threshold level. * ≠ statistically abnormal 32

33. OGMS:disease def. – A disposition (i) to undergo pathological processes that (ii) exists in an organism because of one or more disorders in that organism. 33

34. Clinical abnormality ‘bodily feature’ - an abbreviation for: ‘a physical component, a bodily quality, or a bodily process’. A bodily feature is clinically abnormal = def. (1) is not part of the life plan for an organism of the relevant type (unlike aging or pregnancy), (2) is causally linked to an elevated risk either of pain or other feelings of illness, or of death or dysfunction, and (3) is such that the elevated risk exceeds a certain threshold level.* *Compare: baldness 34

35. Definitions - Foundational Terms Disorder =def. – A causally linked combination of physical components that is clinically abnormal. Pathological Process =def. – A bodily process that is a manifestation of a disorder and is clinically abnormal. Disease =def. – A disposition (i) to undergo pathological processes that (ii) exists in an organism because of one or more disorders in that organism. 35

36. Dispositions and Predispositions All diseases are dispositions; not all dispositions are diseases. A predisposition is a disposition. Predisposition to Disease of Type X =def. – A disposition in an organism that constitutes an increased risk of the organism’s subsequently developing the disease X. HNPCC is caused by a disorder (mutation) in a DNA mismatch repair gene that disposes to the acquisition of additional mutations from defective DNA repair processes, and thus is a predisposition to the development of colon cancer. 36

37. Huntington’s Disease - genetic Etiological process - inheritance of >39 CAG repeats in the HTT gene produces Disorder - chromosome 4 with abnormal mHTT bears Disposition (disease) - Huntington’s disease realized_in Pathological process - accumulation of mHTT protein fragments, abnormal transcription regulation, neuronal cell death in striatum produces Abnormal bodily features recognized_as Symptoms - anxiety, depression Signs - difficulties in speaking and swallowing Symptoms & Signs used_in Interpretive process produces Hypothesis - rule out Huntington’s suggests Laboratory tests produces Test results - molecular detection of the HTT gene with >39CAG repeats used_in Interpretive process produces Result - diagnosis that patient X has a disorder that bears the disease Huntington’s disease 37

38. HNPCC - genetic pre-disposition Etiological process - inheritance of a mutant mismatch repair gene produces Disorder - chromosome 3 with abnormal hMLH1 bears Disposition (disease) - Lynch syndrome realized_in Pathological process - abnormal repair of DNA mismatches produces Disorder - mutations in proto-oncogenes and tumor suppressor genes with microsatellite repeats (e.g. TGF-beta R2) bears Disposition (disease) - non-polyposis colon cancer realized in Symptoms (including pain) 38

39. Definition: Etiology Etiological Process =def. – A process in an organism that leads to a subsequent disorder. Example: toxic chemical exposure resulting in a mutation in the genomic DNA of a cell; infection of a human with a pathogenic virus; inheritance of two defective copies of a metabolic gene The etiological process creates the physical basis of that disposition to pathological processes which is the disease. 39

40. Definitions - Diagnosis Clinical Picture =def. – A representation of a clinical phenotype that is inferred from the combination of laboratory, image and clinical findings about a given patient. Diagnosis =def. – A conclusion of an interpretive process that has as input a clinical picture of a given patient and as output an assertion to the effect that the patient has a disease of such and such a type. 40

41. Definitions - Qualities Manifestation of a Disease =def. – A bodily feature of a patient that is (a) a deviation from clinical normality that exists in virtue of the realization of a disease and (b) is observable. Observability includes observable through elicitation of response or through the use of special instruments. Preclinical Manifestation of a Disease =def. – A manifestation of a disease that exists prior to its becoming detectable in a clinical history taking or physical examination. Clinical Manifestation of a Disease =def. – A manifestation of a disease that is detectable in a clinical history taking or physical examination. Phenotype =def. – A (combination of) bodily feature(s) of an organism determined by the interaction of its genetic make-up and environment. Clinical Phenotype =def. – A clinically abnormal phenotype. 41

42. Big Picture 42

43. Ontology for Mental Health Werner Ceusters University at Buffalo 43

44. 44

45. Ontology for Mental Health V0.0001 Legend representation process continuant disjunction MHOBFO/OGMS 45 some obvious links left out to aid readability

46. Ontology for Mental Health V0.0001 Legend representation process continuant disjunction MHOBFO/OGMS 46

47. M ENTAL P ROCESS (L1,U) =def. B ODILY P ROCESS which brings into being, sustains or modifies a C OGNITIVE R EPRESENTATION or a B EHAVIOR I NDUCING S TATE 47

48. B EHAVIOR (L1,U) =def. a P ROCESS having P ROCESSES as parts in which an O RGANISM participates as agent in response to external or internal stimuli and following some pattern which is dependent upon some combination of that O RGANISM ’s internal state and external conditions. (Derived from the Gene Ontology) 48

49. M ENTAL F UNCTIONING R ELATED A NATOMICAL S TRUCTURE (L1,U) =def. A NATOMICAL S TRUCTURE in which there inheres the D ISPOSITION to be the agent of a M ENTAL P ROCESS 49

50. Mental Functioning Related Anatomical Structure an independent continuant fiat object part of brain + central and peripheral nervous system 50

51. M ENTAL D ISORDER =def. D ISORDER in one or more M ENTAL F UNCTIONING R ELATED A NATOMICAL S TRUCTURES P ATHOLOGICAL M ENTAL P ROCESS =def. P ATHOLOGICAL P ROCESS which is the manifestation of a M ENTAL D ISORDER M ENTAL D ISEASE =def. a D ISEASE which is a D ISPOSITION to undergo P ATHOLOGICAL M ENTAL P ROCESSES 51

52. B EHAVIOR I NDUCING S TATE (L1,U) =def. B ODILY Q UALITY inhering in a M ENTAL F UNCTIONING R ELATED A NATOMICAL S TRUCTURE which leads to B EHAVIOR of some specific sort 52

53. Big Picture 53

54. Big Picture 54

55. Clinical Evaluation Terms Sign =def. – A bodily feature of a patient that is observed in a physical examination and is deemed by the clinician to be of clinical significance. (Objectively observable features) Symptom =def. – An experienced bodily feature of a patient that is observed by and observable only by the patient and is of the type that can be hypothesized by a patient to be a realization of a disease. (A restricted family of phenomena including: nausea, anger, drowsiness, itchiness, anguish, and pain, which are of their nature experienced in the first person) Symptoms are subjective. But this does not mean that there is no objective fact of the matter whether a given symptom exists 55

57. SymptomsSignsPhysical BasisExamples Canonical Pain PCT: Pain with concordant tissue damage Pain Manifestation of tissue damage Signals sent to nociceptive system Activation of emotion- generating brain centers, which can produce increased heart rate, blood pressure, galvanic skin response. Peripheral tissue damage Intact nociceptive system Primary sunburn Pain from strained muscle Pain from fracture Pulpitis Variant Pain PNT: pain without concordant tissue damage Pain Manifestation of some disorder in the patient Signals sent to nociceptive system Patient reports of pain are either exaggerated or muted relative to disorder Activation of emotion generating brain centers Physical disorder of amplitude control mechanisms associated with the nociceptive system Intact nociceptive system Myofascial pain disorder Tension-type headache Chronic back pain NN: neuro- pathic nociception Pain Neurological test confirming nerve damage Disorder in the nociceptive system Trigeminal neuralgia Post-herpetic neuralgia Diabetic neuropathy Central pain PRP: Pain-Related Phenomena Without Pain PBWP: pain behavior without pain ? Report of pain Sick role behaviors accompanied by normal clinical examination Grossly exaggerated pain behaviors Identified external incentives Mental states such as anxiety, rather than peripheral tissue locus Disordered emotional or cognitive systems misinterpreting sensory signals Factitious pain Malingering Anxiety-induced pain report TWP: tissue- damage without pain No pain Manifestation of tissue damage normally of the sort to cause pain Suppression of pain system by one or other mechanism Stress associated with sudden emergencies Physiological damping of the pain process caused by endorphins Placebo-induced opioid analgesia Genetic insensitivity to pain

58. Pain Ontology (PN)

59. Closing remarks about borderline cases The methodology of canonical ontology

60. Where does Mount Everest begin and end? Cf. Barry Smith and David M. Mark, “Do Mountains Exist?”, Environment and Planning B, 30, 2003. 60