During the last three years, we have been investigating how the human brain processes pain-related signals it receives from the body’s internal organs. More recently, we have been examining what differences, if any, occur in the way the human brain processes these signals — both in healthy subjects and in patients suffering from irritable bowel syndrome. Several pieces of evidence suggest that women are more prone to certain chronic pain conditions than men. In the United States, IBS is about twice as common in women than in men, and many other chronic pain conditions such as irritable bladder syndrome and fibromyalgia are also significantly more common in women. Despite these clinical findings, the biological basis underlying these gender differences remains unclear.
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Using positron emission tomography (PET) and corroborative functional magnetic resonance imaging (fMRI), in combination with a protocol to stimulate the colon, investigators at the UCLA/CURE Neuroenteric Disease Program generated the first data to measure regional cerebral activity of intestinal pain in humans. They have also found a disease-specific pattern of alteration of that activity among patients suffering from the most common chronic gastrointestinal condition in the United States, IBS. (For a more detailed account of that work, please see the Los Angeles Times “Science” section’s feature article, 5 September 1996, or the January 1997 issue of Gastroenterology. ) To perform these studies, they employ a balloon catheter that is connected to a programmable pump which delivers precise distension pressures to the colon over fixed periods of time. The catheter is placed in the rectosigmoid colon approximately one hour before the brain imaging sessions. PET scans are then obtained at baseline and during inflation of the balloon to pre-specified distension pressures. Using this technique, the UCLA investigators discovered a failure in patients with IBS to activate a portion of the brain which is called the anterior cingulate cortex. This brain region has several properties which are pertinent to the symptoms of IBS. It has a high number of opiate receptors, suggesting that it plays a crucial role in the body’s ability to inhibit pain by releasing endorphins. It has been identified as the brain region that determines the degree of suffering and unpleasantness associated with pain and it plays an important role in regulating the autonomic nervous system’s response to pain, i.e. in the regulation of heart rate and gastrointestinal motility and secretion. The balance between so-called parasympathetic and sympathetic nerve influences on the digestive system plays an important role in the etiology of constipation and diarrhea. |
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By combining this kind of brain imaging protocol with continuous monitoring of autonomic measures (skin conductance, pulse rate, heartbeat-to-heartbeat variability), measures of perception (stimulus intensity, stimulus unpleasantness, anxiety level) and timed sampling of hormones in the blood (serum levels of estrogen, progesterone, norepinephrine, cortisol, ACTH), they have available a powerful method for establishing in detail the central and peripheral nervous systems’ responses to pain stimuli and how those responses differ between the sexes.
The results of their most recent experiments (so far involving 220 PET scans obtained from 36 subjects equally divided between males and females) indicate that during both actual and anticipated colonic distention, significant differences between the regional cerebral blood flow patterns in the brains of men and women occur. The sex differences are even more dramatic among patients with IBS. Areas that differ most significantly include the anterior left insula, a brain region with close connections to the anterior cingulate cortex and the prefrontal cortex. These three brain regions form a network that is involved in pain processing, and in memory retrieval of past pain experiences and associated emotional and autonomic responses. Thus, the same networks in the brain that process an actual painful stimulus are involved in the formation of complete memories of such events. This may be of importance in view of the common association of IBS with post traumatic stress syndrome (PTSD), a syndrome that develops after an extremely stressful situation during which an individual’s life was threatened (such as war combat exposure, motor vehicle accident or rape). Commonly, affected patients develop a flashback of the traumatic event, triggered by a sound or picture. This flashback is associated with all the emotional, sensory and autonomic responses that were part of the brain’s response to the traumatic stimulus in the first place.
Even though the majority of IBS patients do not have PTSD, it may be that certain life events, food intake or sensations from the gut can trigger memories of past abdominal pain and discomfort, which may have occurred as far back as childhood. Based on our findings it is intriguing to speculate that men and women differ in the degree to which they retrieve such memories in preparation for an anticipated pain from their gut.
If you would like to learn more about our research program, or if you are interested in participating in one our ongoing brain imaging studies, please contact our clinical trials office at (310) 268-3432.