Functional and morphological characteristics of neuronal substance P in the canine gastroesophageal junction.

The specific functions of the numerous substance P (SP) nerve fibers present within the gastrointestinal tract are not clearly defined. This study examines both functional aspects and distribution of immunoreactive SP (IR-SP) in the canine gastroesophageal junctional (GEJ) region. Lower esophageal sphincter pressure (LESP), mean arterial pressure (MAP), pulse rate (PR), and respiratory rate (RR) were monitored before and after topical application of 2 ml capsaicin (8-methyl-N-vanillyl-6-nonenamide) to the distal esophageal mucosa of anesthetized dogs. Animals then underwent a capsaicin desensitization protocol over a 12-day period. The responses of monitored variables were compared on Day 1 and Day 12 of repetitive capsaicin application. Immunohistochemistry and radioimmunoassay (RIA) were performed on GEJ segments to study the distribution and content of IR-SP in both control (untreated) and capsaicin-treated dogs. The IR-SP was extracted from tissue for RIA and analysis by reverse-phase high-performance liquid chromatography (HPLC). On Day 1, a 2-ml capsaicin application stimulated increases in LESP (44.3 +/- 7.8 cm H2O; P < 0.05), MAP (48 +/- 8.7 mm Hg; P < 0.05), PR (52.6 +/- 20.5 beats/min; P < 0.05), and RR (26.3 +/- 15.6 breaths/min; P > 0.2). No response was observed on Day 12 of treatment. This was accompanied by a 43.3% decrease of IR-SP content in the mucosa of the distal esophagus of desensitized animals. Capsaicin applied at greater concentrations on Day 12 stimulated a return of responses (P < 0.05). Ganglia, cell bodies, nerve fascicles, and neurites stained positively for IR-SP. IR-SP content was markedly higher in esophageal mucosa than in gastric mucosa (P < 0.05). The authenticity of the IR-SP molecule was confirmed by elution time on HPLC. In conclusion, repetitive capsaicin application induced a state of homologous desensitization which was accompanied by a partial depletion of mucosal SP. The GEJ region contains a high SP content with a broad neural distribution. These findings are consistent with the hypothesis that SP may act as a neurotransmitter for chemonociceptive stimuli in the canine distal esophagus.