The Effect of a 10-day Course of Transcranial Magnetic Stimulation on Abdominal Pain in Patients With Locally Advanced and Advanced Pancreatic Cancer, a Randomized Phase II Study.

The primary aim of this protocol is to investigate a possible novel treatment for visceral pain in patients with locally advanced or advanced pancreatic cancer. Pain is a major contributor to the poor quality of life in patients with pancreatic cancer. Most patients with locally advanced or advanced pancreatic cancer have abdominal pain that requires treatment with increasing doses of narcotic pain medication. The refractory nature of pancreatic cancer pain to pharmacologic therapy led us to hypothesize that one mechanism leading to pain in these patients is dysfunction of brain cortical regulation of visceral sensation. This notion is supported by the finding that deep electrical stimulation of the brain can produce pain relief in patients with intractable pain due to progressive cancers of various types. In addition, patients with pancreatitis, a non-malignant pancreatic condition causing chronic pain, can continue to experience disabling pain even after total pancreatectomy. These finding suggests that pain symptoms in pancreatic cancer can be sustained by a pancreas-independent, neural-based mechanisms in the brain.

Visceral sensation is processed in the secondary somatosensory area (SII). Therefore, pancreatic cancer pain may be sustained by dysfunction of SII rather than by local effects of the cancer alone. We hypothesize further, that dysfunction of SII is one of hyper-excitability. According to this hypothesis, suppression of SII activity may help control the pain in patients with pancreatic cancer and may provide synergy with pharmacologic treatment.

Temporary inhibition of SII activity can be obtained by a novel, non-invasive procedure called transcranial magnetic stimulation (TMS). TMS can suppress brain excitability beyond the duration of the direct application of TMS if appropriate stimulation parameters are utilized. This hypothesis is supported by a sham controlled, double blind pilot trial of 5 subjects with idiopathic chronic pancreatitis: active rTMS applied to SII resulted in significant pain improvement in three of the subjects while sham did not provide any benefit in any of these patients. Furthermore, recent evidence suggests that stimulation of other brain areas, such as the dorsolateral pre-frontal cortex, can modulate acute, experimentally invoked pain (Graff-Guerrero et al 2005).

We will rigorously test the hypothesis that pain due to pancreatic cancer is sustained by dysfunction of SII characterized by hyperexcitability through two specific aims:

1. The first aim of this study is to examine whether 1Hz repetitive TMS (rTMS) applied to SII for ten days during two consecutive weeks in patients with abdominal pain due to pancreatic cancer has an analgesic effect.