mind body2

Slide 1: 

Mind and body Qasim Aziz Wingate Institute of neurogastroenterology

René Descartes (1596-1650): 

René Descartes (1596-1650) French Mathematician, physiologist and Philosopher

Descarte’s mind body theory: 

Descarte’s mind body theory External motions affect the peripheral ends of the nerve fibrils, which in turn displace the central ends. As the central ends are displaced, the pattern of interfibrillar space is rearranged and the flow of animal spirits is thereby directed into the appropriate nerves. Descartes' credited with the founding of reflex theory.

Cartesian dualism: 

Cartesian dualism In Descartes' conception, the rational soul, an entity distinct from the body and making contact with the body at the pineal gland, might or might not become aware of the differential outflow of animal spirits brought about through the rearrangement of the interfibrillar spaces. When such awareness does occur, however, the result is conscious sensation -- body affecting mind. In turn, in voluntary action, the soul might itself initiate a differential outflow of animal spirits. Mind, in other words, could also affect body

Slide 5: 

Does mind-body interaction modulate visceral function?

Slide 6: 

Historical perspective

Slide 7: 

Historical perspective

Slide 8: 

Historical perspective

Slide 9: 

Colonic response to stress - the bowels are ringing ………. Almy TP, AM J Med. 1951; 10:60

Pain as a model of studying Cartesian Dualism: 

Pain as a model of studying Cartesian Dualism

The components perception of pain!: 

The components perception of pain! Sensory-Discriminative Cognitive-Evaluative Affective- Motivational Melzack and Casey (1968) Melzack and Katz (1994) Emotional Valence Attention Anticipation Intensity Site

Slide 12: 

Functional Brain Imaging

Slide 13: 

Functional brain imaging Cortical Evoked Potentials (CEP) Magnetoencephalograpy (MEG) Positron Emission Tomography functional Magnetic Resonance Imaging

Slide 14: 

Excellent Spatial res (2-5mm), poor temporal res (4-8 msec)

Slide 15: 

Oesophageal stimulation

Slide 16: 

Cortical representation of oesophageal pain Sensory cortex Insular cortex Ant. Cingulate Cortex / prefrontal cortex Aziz et al. J Neuroscience 2000

Slide 17: 

Emotions

Emotional context: facial Expressions!!!: 

Emotional context: facial Expressions!!!

Neural correlates of emotional context: 

Neural correlates of emotional context Phillips et al (1997) Nature. 389: 495-498. Fear Disgust

Hypothesis: 

Hypothesis Negative emotional context will modulate the brain processing of oesophageal sensation

Experimental condition 1: 

Experimental condition 1 Neutral face + OS

Experimental condition 2Fearful face +OS: 

Experimental condition 2Fearful face +OS

Results: 

Results Philips et al. Brain. 2003

Slide 24: 

Anticipation

Slide 25: 

Ivan Pavlov ~ Classical Conditioning Learned autonomic responses can be produced in the GI tract to external stimuli Conditioning Procedure Physiological Response Food => Salivation During Conditioning (Learning) Bell + Food => Salivation Anticipation Bell => Salivation Extinction Bell => No response

Learning phase: 

Learning phase (20 trials)

Anticipation phase: 

Anticipation phase (10 Trials) No Pain (10 Trials) Randomised

Slide 28: 

Results - learning phase Gregory et al. IASP. 2002. poster no: 1110-p26

Slide 29: 

Results - anticipation phase Gregory et al. IASP. 2002. poster no: 1110-p26

Clinical relevance: 

Clinical relevance

Functional gut disordersNCCP, FD, IBS: 

Functional gut disordersNCCP, FD, IBS Unexplained abdominal symptoms Any gut organ can be involved Pain is the commonest symptom Expensive to treat - $8 billion/year in USA

Slide 32: 

IBS Visceral hypersensitivity Whitehead et al. Dig Dis Sci. 1980

Functional gut disorders: 

Functional gut disorders Past history of gut inflammation or injury Post infective Post surgical Inflammatory bowel disease 50-80% -Psychological Disorders Anxiety Depression Somatisation Panic Disorders

Slide 34: 

Abnormal brain processing Emotions : Depression Anxiety Cognition : Hypervigilance

Slide 35: 

Sensitisation

Mechanisms of nerve sensitisation: 

Mechanisms of nerve sensitisation

Slide 37: 

Peripheral nerve terminal Cell Body Dorsal Horn Synapse Glutamate Mechanism of pain transmission NMDA Decreases threshold of activation Increase receptive field

Slide 38: 

Somatic hypersensitivity Injured Tissue Non Injured Tissue 2 1 (Primary Hyperalgesia) (Secondary Hyperalgesia)

Slide 39: 

FGID - Sensitization

Does the gut get injured?: 

Does the gut get injured?

Slide 41: 

Model of visceral hypersensitivity 15cm pH probe Electrical Stimulating Electrode pH probe Infusion port pH Pre Infusion pH During Infusion Acid Acid Saline Saline

Slide 42: 

Sarkar et al. Lancet 2000 Central sensitization Upper oesophagus Time (Hours) Saline Saline Acid Acid 30 min Pain Tolerance Pain Tolerance Δ Pain Threshold

Anxiety and sensitisation: 

Anxiety and sensitisation Relationship between baseline anxiety score and magnitude of sensitisation in the proximal oesophagus after acid (n=14) Max change in PT (mA) Baseline SAI score r = -0.572 p = 0.03

What is the evidence for gut inflammation in FGID?: 

What is the evidence for gut inflammation in FGID?

Slide 45: 

IBS - Post-infection Gut Dysfunction Gwee et. al., Gut 1999; 44:400

Increased plasma pro-inflammatory cytokines in IBS: 

Dinan TG et al, Gastroenterology 2006 Increased plasma pro-inflammatory cytokines in IBS

Post-infection Gut Dysfunction - Psychological Scores: 

IBS - Post-infection Gut Dysfunction Post-infection Gut Dysfunction - Psychological Scores Gwee et. al., Gut 1999; 44:400

The role of stress: 

The role of stress

Slide 49: 

parasympathetic Stress autonomic nervous system Enteric nervous system sympathetic glucocorticoids adrenaline, noradrenaline medulla adrenal gland higher cortical structures hypothalamus pituitary CRF ACTH cortex Gut immune cells Brain-gut axis PSYCHONEUROIMMUNOLOGY pons

Relationship between the brain and immune system is reciprocal: 

Relationship between the brain and immune system is reciprocal Brain NPs Hormones Neurotransmitters Cytokines NPs

Slide 52: 

Sternberg, Nat Rev Immuno 2006

Potentiation of inflammation induced epithelial permeability by stress: 

Potentiation of inflammation induced epithelial permeability by stress

Slide 55: 

To understand ‘gut feelings’……..

Warning !: 

Warning !

Acknowledgements: 

Acknowledgements University of Manchester, GI Sciences Professor David Thompson, Sanchoy Sarkar, Anthony Hobson, Robert Willert, Phillip Mathews Institute of Psychiatry, London Steven Williams, Lloyd Gregory, Lidia Yaqez, Mary Phillips, Steve Coen, Virginia Ng,