Activation of nociceptive neurons in T9 and T10 in cerulein pancreatitis.

Mechanisms of pain transduction in acute pancreatitis are poorly understood. Increased Fos expression in the spinal cord is a marker of activation of nociceptive neurons. We hypothesized that cerulein pancreatitis leads to increased Fos expression at T9 and T10, which receive sensory input from the pancreas. Rats were injected with cerulein (100 microg/kg, s.c.) or saline carrier (NS). Endpoints at 4, 6, and 10 h were serum amylase, myeloperoxidase activity (MPO), and spinal cord Fos expression (number of immunoreactive nuclei/section dorsal gray matter). Fos-like immunoreactivity (FLI) at T9-T10 was compared to internal controls (T6, T12). An average of 20 spinal cord histologic sections were evaluated per rat. Some animals were injected with the mu-opioid receptor agonist, buprenorphine (90 microg/kg, s.c.), 3 h after cerulein, and their endpoints were measured at 6 h. Analysis of variance and t tests were used for statistical analysis. Results are means +/- SEM. As expected, cerulein induced edematous pancreatitis, with a 4-fold increase in serum amylase at 6 h [cer (n = 8): 14,000 +/- 1,300 U/ml versus NS (n = 10): 3,700 +/- 300, P < 0.005)] and a 2-fold increase in MPO activity (0.25 +/- 0.05) activity units/dry wt versus 0.13 +/- 0.02, P < 0.05). Cerulein induced nearly a 2-fold increase in FLI at T9 and T10 [n = 10 (cer) and n = 13 (NS): T9, 14 +/- 1.5 versus 7.8 +/- 0.88; T10, 15 +/- 1.7 versus 8.3 +/- 0.70; P < 0.05]. Peak effects of cerulein on FLI occurred at 6 h and were greatest at T9/T10 with relative sparing of T6/T12. T6/T12 expression was similar in experimental and control groups. Buprenorphine significantly reduced both serum amylase and FLI and T9/T10. Cerulein-induced acute pancreatitis in rat increases visceral nociceptive signaling at spinal cord levels T9 and T10, with a peak at 6 h. Blockade of this effect by the mu-opioid receptor agonist buprenorphine could occur either by direct activation of central opioid receptors and/or an anti-inflammatory mechanism. FLI is a useful tool for studying the pathophysiology of pain in experimental acute pancreatitis.

Prior exposure to phencyclidine decreases voluntary sucrose consumption and operant performance for food reward.

Prior exposure to the psychotomimetic drug phencyclidine (PCP) produces a number of schizophrenia-like behaviors in animals. The goal of the present study was to determine whether prior exposure to PCP produces decreased reward function, thereby modeling one aspect of negative schizophrenic symptomatology. To this aim, the consequences of prior exposure to PCP were assessed on two types of appetitive consumptive behavior. In the first set of experiments, the effects of PCP (15 mg/kg, 20 h before testing) on sucrose consumption were tested for three consecutive days under conditions of deprivation and nondeprivation. In the deprivation condition, animals were water deprived for 4 h prior to injection of PCP or saline (SAL). Twenty hours following the injection (24 h after the onset of water deprivation), animals were allowed access to either 5% sucrose or water for 30 min. In the nondeprivation condition, 5% sucrose consumption was measured for 30 min, 20 h after PCP or SAL injection and water consumption was measured during the 23.5 h preceding sucrose consumption. PCP decreased both sucrose and water consumption under deprivation conditions on the second and third day of testing but selectively decreased sucrose consumption under nondeprivation conditions on all three testing days. LiCl (50 mg/kg, 20 h before testing) did not significantly reduce sucrose consumption in the nondeprivation paradigm, indicating that the effect of PCP was not due to conditioned taste aversion. In the second experiment, PCP (15 mg/kg, 20 h before testing) decreased operant performance when animals were switched from a continuous reinforcement schedule of food delivery to a fixed ratio (FR4) schedule. Apomorphine (APO, 30 microg/kg, 30 min before testing), a positive control, induced a similar performance deficit. However, the PCP-induced deficit was not apparent until the third day of FR4 testing while the APO deficit was apparent on the first day. The effects of PCP on sucrose consumption demonstrate PCP-induced decreases in reward function. However, the delayed appearance of the PCP-induced decrease in operant performance suggests that these results may be better explained by a PCP-induced attentional deficit, also characteristic of schizophrenic psychopathology.