Intradermal Injection with Nerve Growth Factor: A Reproducible Model to Induce Experimental Allodynia and Hyperalgesia.

BACKGROUND: Nerve growth factor (NGF) plays a pivotal role in survival, growth, and differentiation of the nervous system. Increased levels of NGF have been reported in human pain disorders. Experimental injection of NGF in humans is known to evoke long-lasting mechanical sensitization and subsequent allodynia and hyperalgesia. METHODS: Reproducibility of intradermal injection of NGF was investigated. Twenty healthy male volunteers were included (mean age 24 years, range 19 to 31). The experiment consisted of 3 identical treatment periods with period 1 stimulating the right arm, period 2 the left arm, and period 3 stimulating the right arm again (period one and three were separated by at least 21 days). Pain intensity was assessed in response to several phasic stimuli in 3 adjacent sites of the volar forearm: pressure; pinprick; brush; and heat before and after NGF injection. Additionally, areas of allodynia and secondary hyperalgesia were assessed. Rekindling with pressure was performed 1 hour and 24 hours after injection. Reproducibility was assessed with intraclass correlation coefficient (ICC 3,1). RESULTS: ICC values > 0.6 for all phasic stimuli and for the area of hyperalgesia. After NGF injection, pressure pain (P < 0.001) and heat pain (P < 0.01) sensitivity increased significantly. After rekindling, the area of hyperalgesia (von Frey 26 g) was significantly increased (P = 0.03) and sensitivity to pinprick was increased (P < 0.02). CONCLUSION: Intradermal NGF injection is capable of inducing reproducible allodynia and hyperalgesia, and the model is recommended for future experimental and pharmacological pain studies.

Pain severity reduces life quality in chronic pancreatitis: Implications for design of future outcome trials.

BACKGROUND/OBJECTIVES: Chronic pancreatitis (CP) is a disabling disease characterised by abdominal pain, and various pancreatic and extra-pancreatic complications. We investigated the interactions between pain characteristics (i.e. pain severity and its pattern in time), complications, and quality of life (QOL) in patients with CP. METHODS: This was a cross-sectional study of 106 patients with CP conducted at two North European tertiary medical centres. Detailed information on clinical patient characteristics was obtained from interviews and through review of the individual patient records. Pain severity scores and pain pattern time profiles were extracted from the modified brief pain inventory short form and correlated to QOL as assessed by the EORTC QLQ-C30 questionnaire. Interactions with exocrine and endocrine pancreatic insufficiency, as well as pancreatic and extra-pancreatic complications were analysed using regression models. RESULTS: Pain was the most prominent symptom in our cohort and its severity was significantly correlated with EORTC global health status (r = -0.46; P < 0.001) and most functional and symptom subscales. In contrast the patterns of pain in time were not associated with any of the life quality subscales. When controlling for interactions from exocrine and endocrine pancreatic insufficiency no effect modifications were evident (P = 0.72 and P = 0.85 respectively), while the presence of pancreatic and extra-pancreatic complications was associated with an almost 15% decrease in life quality (P = 0.004). CONCLUSIONS: Pain severity and disease related complications significantly reduce life quality in patients with CP. This information is important in order to design more accurate and clinical meaningful endpoints in future outcome trials.