Werner CEUSTERS Center of Excellence in Bioinformatics and Life Sciences Ontology Research Group

1. Meeting on Pain and Neurological Disease OntologiesFoundations for an Ontology for pain-related disablement, mental health and quality of life (OPMQoL) SUNY at Buffalo - January 20, 2012 Werner CEUSTERS Center of Excellence in Bioinformatics and Life Sciences Ontology Research Group University at Buffalo, NY, USA http://www.org.buffalo.edu/RTU

2. Acknowledgement The work described is funded in part by grant 1R01DE021917-01A1 from the National Institute of Dental and Craniofacial Research (NIDCR). The content of this presentation is solely the responsibility of the author and does not necessarily represent the official views of the NIDCR or the National Institutes of Health.

3. Collaborators Werner Ceusters – Richard Ohrbach UB (PIs) Mike T. John – Eric L. Schiffman University of Minnesota Vishar Aggarwal Manchester, UK Joanna Zakrzewska London, UK Thomas List Malmö, Sweden Rafael Benoliel Hadassah, Israel

4. Background (1) • July 2008, Toronto: • the International RDC/TMD Consortium Network identified a need to incorporate the RDC/TMD diagnostic taxonomy into a comprehensive orofacial pain taxonomy. • April, 2009, Miami: • ‘The International Consensus Workshop: Convergence on an Orofacial Pain Taxonomy’ participants decided that an adequate treatment of the ontology of pain in general, and orofacial pain in particular, together with an appropriate terminology, is mandatory to advance the state of the art in diagnosis, treatment and prevention. Ohrbach R, List T, Goulet J, Svensson P. Recommendations from the International Consensus Workshop: Convergence on an Orofacial Pain Taxonomy. Journal of Oral Rehabilitation. 2010.

5. Background (2) • The following consecutive steps were proposed: • study the terminology and ontology of pain as currently defined, • find ways to make individual data collections more useful for international research, • develop an ontology for integrating knowledge and data over all the known basic and clinical science domains concerning TMD and its relationship to complex disorders, and • expand this ontology to cover all pain-related disorders.

6. Potential impact • Improvements anticipated: • Better assessment of quality of life and disablement in relation to pain, • Increasing the reliability and validity of the Research Diagnostic Criteria for TMD, • Better methods and tools for unambiguous data annotation and classification for pain; • Expected changes in the field: • Better use of self-report assessment approaches for functional limitation and psychosocial disability related to pain, • Widespread use of an adequate terminology and ontology of disease and disease perception.

7. Project goals • to obtain better insight into: • the complexity of pain disorders, pain types as well as pain-related disablement and • its association with mental health and quality of life, • to develop an ontology for this subdomain incorporating a broad array of measures consistent with a biopsychosocial perspective regarding pain, • to integrate five existing datasets that broadly encompass the major types of pain in the oral and associated regions.

8. Specific Aims • describe the portions of reality covered by the five datasets by means of a realism-based ontology (OPMQoL), • design bridging axioms required to express the data dictionaries of the datasets in terms of the OPMQoL and translate these axioms in the query languages used by the underlying databases, • validate OPMQoL by querying the datasets with and without using the ontology and by comparing the results in function of the clinical question identified, • document the development and validation approach in a way that other groups can re-use and expand OPMQoL, and use our approach in other domains.

9. Starting point: IASP definition for ‘pain’ • ‘an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage’; • what asserts: • a common phenomenology (‘unpleasant sensory and emotional experience’) to all instances of pain, • the recognition of three distinct subtypes of pain involving, respectively: • actual tissue damage, • what is called ‘potential tissue damage’, and • a description involving reference to tissue damage.

10. Five pain-related phenomena Smith B, Ceusters W, Goldberg LJ, Ohrbach R. Towards an Ontology of Pain. In: Mitsu Okada (ed.), Proceedings of the Conference on Logic and Ontology, Tokyo: Keio University Press, February 2011:23-32.

11. Pain with concordant tissue damage =def.: (1) a bodily process in an organism S involving two integrated levels: (1a) activation of the nociceptive system including the pain-associated emotion-generating brain components of S, and (1b) a simultaneous sensory and aversive experience on the part of S  that is (2) caused by damage to tissue located in a region R of the body of the subject S, (3) experienced by S as being caused by this damage, (4) such as to involve an aversive reaction on the part of S directed towards that which is presumed by S to be causing this damage, (5) concordant with the tissue damage on both levels (1a) and (1b), and also (6) such that the sensory experience is sufficiently intense to communicate the presence of tissue damage to the subject. Smith B, Ceusters W, Goldberg LJ, Ohrbach R. Towards an Ontology of Pain. In: Mitsu Okada (ed.), Proceedings of the Conference on Logic and Ontology, Tokyo: Keio University Press, February 2011:23-32.

12. Tissue damage sensing and pain generation David Julius & Allan I. Basbaum . Molecular mechanisms of nociception. Nature Vol 413, 13 Sept 2001

13. Current general definition for ‘pain’ (1) • pain =def. a bodily process in an organism S involving two integrated levels: • (a) activation of the nociceptive system and associated emotion generating brain components of S, and • (b) a simultaneous aversive sensory and emotional experience on the part of S, • where (b) is phenomenologically similar to the sort of aversive experience involved in PCT pain. Smith B, Ceusters W, Goldberg LJ, Ohrbach R. Towards an Ontology of Pain. In: Mitsu Okada (ed.), Proceedings of the Conference on Logic and Ontology, Tokyo: Keio University Press, February 2011:23-32.

14. Current general definition for ‘pain’ (2) • ‘phenomenologically similar’ means inter alia: • (1) that the experience is ‘of’ or is ‘targeted towards’ some region R of the body of S, so that all pain is in this sense (and however diffusely) localized; • (2) that the experience involves a dimension of unpleasantness which – as is shown by the case of pain asymbolia – is not necessarily of the sort that involves suffering or aversion on the part of the subject S. Smith B, Ceusters W, Goldberg LJ, Ohrbach R. Towards an Ontology of Pain. In: Mitsu Okada (ed.), Proceedings of the Conference on Logic and Ontology, Tokyo: Keio University Press, February 2011:23-32.

15. PNT: pain without concordant tissue damage • pain associated with some (past) disorder outside the nociceptive system, • this disorder being predominantly associated with peripheral trauma (e.g. myofacial pain), or predominantly not (for example tension headache) , • the pain being marked by discordances in terms of some attribute, such as intensity, spatial extent, or episode frequency or duration, relative to the state of the underlying tissue, • with intact nociceptive system though possibly ramped up or down (e.g. pain asymbolia) to what would be the normal (PCT) case.

16. Neuropathic nociception • pain caused by some disorder in the nociceptive system, • may be experienced as having a peripheral cause, (e.g. phantom limb pain).

17. Pain-related phenomena • PBWP: pain behavior without pain: there is, for example, a mere report in a medical record attributed to the statements of a patient, but no pain is being experienced by the patient (a fact which may or may not be detectable by an external observer). • TWP: Tissue-damage without pain: tissue damage normally of the sort to cause pain does not activate the pain system (as contrasted with pain asymbolia, where pain is experienced, so that the pain system is activated, but the patient does not experience the pain as something that is suffered).

18. Considered datasets • ‘US Dataset’ (724 patients) resulted from the NIH funded RDC/TMD Validation Project, • ‘Hadassah Dataset’ (306 patients) from the Orofacial Pain Clinic at the Faculty of Dentistry, Hadassah, • ‘German Dataset’ (416 patients) of patients seeking treatment for orofacial pain at the Department of Prosthodontics and Materials Sciences, University of Leipzig, • ‘Swedish Dataset’of 46 consecutive Atypical Odontalgia (AO) patients recruited from 4 orofacial pain clinics in Sweden as well as data about age- and gender-matched control patients, 35 of which being painless and 41 being TMD patients, • ‘UK Dataset’ (168 patients) of facial pain of non dental origin present for a minimum of three months.

19. Technical questions to be answered • Q1: To what extent do the data sets and used assessment tools overlap? • Q2: Given that these distinct artifacts refer to the entities on the side of the patient primarily implicitly, indirectly and in different ways, how can this overlap be made explicit and quantifiable? • Q3: How can this overlap be made understandable to software agents in such a way that they can use the corresponding representations of the entities as a basis for meaningful computations, including making comparisons and deriving new information? • Q4: How can we demonstrate that our approach is successful? • Q5: How can we ensure that our work is extensible and the methodology applied easy transferable to other assessment tools and data sets?

20. Old style terminology continues

21. Challenges • (1) which terms used in the domain correspond with real entities, • (2) what real entities need to exist for certain signs and symptoms to manifest themselves, • (3) to what degree do distinct pain disorders lead to similar types of signs and symptoms, and • (4) to what extent can individual patients be suffering from distinct pain disorders at the same time, yet exhibiting manifestations that can be explained by the presence of only one particular pain disorder.

22. PDAP: ‘persistent dento-alveolar pain disorder’ • Key features: patient report of … • episode(s) of dysesthesia, otherwise referred to as "pain" which: • is anatomically located in the dento-alveolar region innervated by the trigeminal nerve • exhibits a continuous or near continuous temporal course • is present more often than not • is not primarily characterized by acute paroxysms • cannot be explained by the presence of another disease or disorder Nixdorf D, Drangsholt M, Ettlin D, Gaul C, de Leeuw R, Svensson P, Zakrzewska J, DeLaat A, Ceusters W. Classifying orofacial pains: a new proposal of taxonomy based on ontology. Journal of Oral Rehabilitation 2011

23. ‘Simple’ ontological perspective on PDAP criteria

24. Data – Terminology – Ontology

25. Mapping assessment instrument terms, ontology and patient cases

26. Current ‘pastime’ • Full ontological analysis of IASP definitions and their evolution since 1994. • (spreadsheet) • Trying to receive data dictionaries. • Analysis of assessment scales and procedure manuals.