Serum concentrations of substance P in cholestasis

Substance P (SP) is an excitatory neuropeptide that acts via the neurokinin-1 receptor (NK-1) in the nervous system. Pruritus, a complication of cholestasis, is a nociceptive stimulus; thus, we hypothesized that cholestasis would be associated with increased neurotransmission via SP as evidenced, in part, by increased serum concentrations of this neuropeptide. Accordingly, the aim of this study was to determine the serum concentration of SP in patients with pruritus secondary to cholestasis and in the serum of rats with cholestasis secondary to bile duct resection (BDR). The mean serum SP concentration of patients with chronic liver disease (CLD) and pruritus was 9.09 pg/mL SD +/- 6.5, significantly higher than 0.74 pg/mL SD +/- 0.77, the mean serum concentration of SP from patients with CLD without pruritus (p = 0.0001), and from that of the control group, which was 0.65 pg/mL SD +/- 0.37 (p = 0.0001). The mean serum SP concentration from six rats with cholestasis secondary to BDR six and fourteen days after surgery was 57.9 pg/mL, SD +/- 17.3, and 56.3 pg/mL, SD +/- 21.4, respectively, as compared to the concentration from the sham resected control group, which was 3.5 pg/mL SD +/- 0.59 (p = 0.002) at six days post surgery. In conclusion, in cholestasis, there is increased availability of SP. These data provide a rationale for the study of SP release and metabolism in cholestasis, and in the mediation of the pruritus.