Patients with chronic pancreatitis show decreased cortical thickness in five areas of the brain known to be involved in the processing of visceral pain, Dr. Jens Brondum Frøkjær and his colleagues reported in the April issue of Clinical Gastroenterology and Hepatology.
Moreover, these reductions in cortical thickness correlated with scores in the patients’ pain diaries, so that patients with the most pain showed the greatest cortical thinning on MRI.
The findings indicate that the chronic pain caused "structural reorganization of the neuromatrix expressed as regional differences in cortical thickness," wrote Dr. Frøkjær of the department of gastroenterology and hepatology and the department of radiology at Aalborg (Denmark) Hospital and Aarhus University Hospital, and his associates (Clin. Gastroenterol. Hepatol. 2011 [10.1016/j.cgh.2011.11.024]).
Their study results further suggest that MRI measurements of cortical thickness, which they characterized as quick and relatively easy to obtain, may serve as a valid indicator of "the overall damage and dysfunction of the pain system."
Dr. Frøkjær and his colleagues assessed cortical thickness in patients with chronic pancreatitis using the same high-resolution three-dimensional MRI technique that other investigators have used when assessing brain changes in patients with the chronic pain of irritable bowel syndrome or trigeminal neuropathy. The recently improved methods now permit "accurate, robust, and rapid analysis of cortical thickness," they said.
The investigators assessed 19 adults with chronic pancreatitis and 15 healthy volunteers matched for age and gender who served as control subjects. All the study subjects completed pain diaries for 1 week before undergoing brain MRI.
Compared with controls, the pancreatitis patients showed cortical thinning in the secondary somatosensory cortex (the Rolandic operculum), the dorsolateral prefrontal cortex (the middle frontal gyrus), the laterofrontal cortex (the orbital parts of the superior and inferior frontal gyrus), the midsection of the cingulate cortex, and the insula.
In previous studies, activation of the secondary somatosensory cortex has been linked to patients’ efforts to attend to and to rate the strength and quality of pain. The prefrontal cortex is central to the processing of visceral pain and "the cognitive aspects of the pain experience," and the frontal cortex receives sensory inputs and is involved in pain processing. The middle cingulate cortex is thought to connect with the hypothalamus and the periaqueductal grey matter "as part of the descending pain modulation system," and the insula is involved in integrating visceral sensory and motor function as well as transmitting pain input to the frontal cortex.
In contrast, no differences between patients and controls were seen in cortical thickness in a control area of the brain – the occipital middle sulcus – that is not involved in central nervous system processing of pain.
Cortical thinning in the five areas of interest were found to correlate with patients’ clinical pain scores.
There were no correlations between cortical thickness and several factors that may have contributed to pancreatic pain, such as excessive alcohol use, the presence of diabetes, and the use of opioid treatments. Cortical thickness also was no different between patients who reported a continuous pattern of pancreatic pain and those who instead suffered discrete attacks of pancreatic pain.
These findings all suggest that the ongoing pain input to the brain results in structural reorganization of the neuromatrix, which has also been proposed to occur in other diseases characterized by chronic pain. The cortical thinning "could be a result of neuroplasticity induced by sustained chronic pain and of increased synaptic activity in the brain’s pain matrix related to the greater inhibitory activity generated to counterbalance the nociceptive input," the researchers said.
However, it is also possible that other factors related to pancreatitis may have contributed to these structural brain alterations. This study could not address that question because there was no matching control group of patients with pancreatitis who did not have abdominal pain. "Such patients are very difficult to find," Dr. Frøkjær and his colleagues noted.
This study was supported by the Karen Elise Jensen Foundation, SparNord Foundation, the Obelske Family foundation, and Heinrich Kopp. No relevant financial conflicts of interest were reported.