review of literature on clinical pancreatology - The Pancreapedia

[266].The chemokine fractalkine induces migration <strong>of</strong> inflammatory cells into inflamed tissues,thereby aggravating inflammatory tissue damage and fibrosis. Furthermore, fractalkineincreases neuropathic pain through glial activation, which can be diminished by blocking <strong>of</strong>its receptor, CX3CR1, through neutralizing antibodies. As chronic pancreatitis ischaracterized by tissue infiltration <strong>of</strong> inflammatory cells, fibrosis, pancreatic neuritis andsevere pain, the roles <strong>of</strong> fractalkine and CX3CR1 were investigated in CP (n=61) and normalpancreas (NP, n=21) by QRT-PCR, western blot and immunohistochemistry analyses. Theirexpression correlated with the severity <strong>of</strong> pancreatic neuritis, fibrosis, intrapancreatic nervefiber density and hypertrophy, pain, CP duration and with the amount <strong>of</strong> inflammatory cellinfiltrate immuno-positive for CD45 and CD68. Advanced fibrosis was associated withincreased fractalkine expression, whereas in vitro fractalkine had no significant impact oncollagen-1 and alpha-SMA expressions in hPSCs. Therefore, pancreatic fractalkineexpression appears to be linked to visceral pain and to the recruitment <strong>of</strong> inflammatory cellsinto the pancreatic tissue and nerve fibers, with subsequent pancreatic neuritis. However,pancreatic fibrogenesis is probably indirectly influenced by fractalkine. Taken together, thesenovel findings suggest that CX3CR1 represents a potential novel therapeutic target to reduceinflammation and modulate pain in chronic pancreatitis [267].Medical pain treatmentThe aim <strong>of</strong> one study was to evaluate the efficacy <strong>of</strong> intrathecal narcotics pump (ITNP) as analternative treatment for patients with pain from chronic pancreatitis. ITNP <strong>of</strong>fers theadvantages <strong>of</strong> reversibility, lower total narcotic dose, and the pancreas remaining intact.Thirteen patients (8 female, 5 male), with mean age 41 years, who had experiencedintractable upper abdominal pain from chronic pancreatitis were <strong>review</strong>ed. Each patient hadmultiple other failed treatment modalities, including partial pancreatic resection (n=6). Theywere <strong>of</strong>fered ITNP after a successful intraspinal opioid trial. Etiologies <strong>of</strong> the pancreatitisincluded idiopathy (n=3), cystic fibrosis (n=2), alcohol (n=2), and pancreas divisum (n=6).The median duration <strong>of</strong> severe, intractable pain prior to ITNP was 6 years (2-22 years). Themedian follow-up time after ITNP was 29 months (range, 7-94 months). The ITNP was in situfor a mean duration <strong>of</strong> 29 months (range, 0.5-94 months). Seven patients had pumpexchange or removal for various reasons; improvement <strong>of</strong> pain at month 53 (n=1), meningitis(n=1), meningitis with subsequent replacement (n=1), pump failure at month 31, 68, 79, and84 (n=4). There were no deaths. The mean pain score prior to implantation was significantlyhigher than 1 year after and last follow-up. The median oral narcotic dose before and 1 yearafter ITNP were morphine sulfate equivalents 338 mg per day (range, 68-1320) and 40 mgper day (range, 0-1680), respectively. Two patients were considered failures, as they stillrequire a high dosage <strong>of</strong> both oral and intrathecal medications to control their pain, despitesignificant pain-score improvement. One patient who was excluded due to meningitis wasalso considered a failure. Therefore, the overall success rate <strong>of</strong> ITNP based on an intentionto-treatanalysis was 77 percent (10/13). The major complications <strong>of</strong> ITNP were centralnervous system infection requiring pump removal (n=1), cerebrospinal fluid leak requiringlaminectomy (n=1), and perispinal abscess with bacterial meningitis requiring pump removal(n=1) [268].Pancreatic enzymes as treatment for painThe multiple possible etiologies <strong>of</strong> painful chronic pancreatitis combined with the likelihoodthat many patients with the condition are addicted to alcohol (and possibly continue to abusealcohol) make clinical research in this field particularly challenging. Additionally, the biologicbasis <strong>of</strong> pain in chronic pancreatitis remains somewhat controversial. Multiple other