Studies of human psycho-physiological responses to visceral pain.

Nature of proposed research: while pain is a common human experience, our tolerance to it varies. This is because factors that influence pain perception such as life experiences, mental state and our genes, differ between individuals. Furthermore, when we perceive pain different parts of the nervous system are activated. These include nerves that carry pain signals from the body to the brain, control organ function e.g. heart and gut, and those that control the secretion of hormones such as cortisol that help combat stress.
In our preliminary studies, we induced pain by blowing up a balloon in the healthy human oeosphagus (gullet) while we measured the activity of nerves that control the heart. We demonstrated that the activity of the vagus nerve which slows down the heart increased in some subjects and decreased in others. Interestingly, subjects who showed an increase in activity were in general more anxious and worried than those who showed a decrease in activity. These results suggest that two distinct populations exist in the way they respond to pain. We now want to carry out studies in a larger number of subjects to determine how prevalent the two types of responses to pain are and also to determine whether a particular response in an individual is reproducible over time. Furthermore we want to determine whether the hormonal response (cortisol levels) to stress is different in the two types of individuals and whether they also differ in the degree to which their oesophagus becomes sensitive after injury with acid. Finally we want to determine if patients who have chronic pain arising from the oesophagus but in whom no cause can be identified also demonstrate the same two types of response to pain as healthy subjects. We will also determine whether individuals who behave differently to pain do so because they have different genes from others.
Prospective outcomes: we anticipate that this research will improve our understanding of why individuals differ in their response to pain and also whether certain individuals are more likely to developing chronic pain conditions.
Expected benefit to human health: if certain individuals are more at risk of developing chronic pain then treatment strategies can be developed based on the reasons leading to this increase in risk, and preventative measures can then be taken to protect these individuals from environmental influences that may predispose them to the development of chronic pain conditions.

Background: Pain perception depends on the interaction between the psychological state and trait of the individual with physiological responses in the Autonomic Nervous System (ANS) and the Hypothalamic Pituitary Axis (HPA). Our preliminary healthy subject studies suggest that two distinct ANS responses to visceral pain occur. Subjects with an increase in Cardiac Vagal Tone (CVT) have more pain-susceptible psychological traits (group A) compared with those who show a decrease in CVT (group B). Primary aim: to determine the prevalence and stability of the psychophysiological response to visceral pain in health. General hypothesis: there will be phenotypic differences in the psychophysiolgical response to visceral pain and these phenotypes will respond differently to psychophysiological stress and to transient oesophageal injury/inflammation. Similar phenotypes will exist in patients with chronic oesophageal pain.
Questions to be addressed:
1. What is the prevalence and stability of the psycho-physiological phenotypes to visceral pain?
2. Do these psycho-physiological phenotypes differ:
a. in their ANS and HPA response to psychological and physiological stress?
b. in the magnitude of central sensitisation to transient injury?
c. in their cortical processing of sensation?
3. Do similar psycho-physiological phenotypes exist in patients with chronic oesophageal pain as in the healthy population?
Methods: study 1: in healthy subjects prevalence and stability of group A and B psychophysiolgical response to visceral pain will be assessed over time. Study 2: In groups A and B the: a) effect of physiological (35% CO2 inhalation) and psychological stress (Trier Social Stress Task) b) the magnitude of secondary allodyina to oesophageal acidification and c) the cortical response (using Magnetoencephalography) to psychological and sensitising stimuli will be assessed. Study 3: In patients with Non cardiac chest pain, the prevalence of psychophysiological profiles identified in healthy subjects will be assessed.
Outcome: these studies will lead to identification of risk factors for the development of chronic pain.