Differential effects of intragastric acid and capsaicin on gastric emptying and afferent input to the rat spinal cord and brainstem.
BACKGROUND
Hydrochloric acid (HCl) is a potential threat to the integrity of the gastric mucosa and is known to contribute to upper abdominal pain. We have previously found that gastric mucosal challenge with excess HCl is signalled to the rat brainstem, but not spinal cord, as visualized by expression of c-fos messenger ribonucleic acid (mRNA), a surrogate marker of neuronal excitation. This study examined whether gastric mucosal exposure to capsaicin, a stimulant of nociceptive afferents that does not damage the gastric mucosa, is signalled to both brainstem and spinal cord and whether differences in the afferent signalling of gastric HCl and capsaicin challenge are related to different effects on gastric emptying.


RESULTS
Rats were treated intragastrically with vehicle, HCl or capsaicin, activation of neurons in the brainstem and spinal cord was visualized by in situ hybridization autoradiography for c-fos mRNA, and gastric emptying deduced from the retention of intragastrically administered fluid. Relative to vehicle, HCl (0.5 M) and capsaicin (3.2 mM) increased c-fos transcription in the nucleus tractus solitarii by factors of 7.0 and 2.1, respectively. Capsaicin also caused a 5.2-fold rise of c-fos mRNA expression in lamina I of the caudal thoracic spinal cord, although the number of c-fos mRNA-positive cells in this lamina was very small. Thus, on average only 0.13 and 0.68 c-fos mRNA-positive cells were counted in 0.01 mm sections of the unilateral lamina I following intragastric administration of vehicle and capsaicin, respectively. In contrast, intragastric HCl failed to induce c-fos mRNA in the spinal cord. Measurement of gastric fluid retention revealed that HCl suppressed gastric emptying while capsaicin did not.


CONCLUSIONS
The findings of this study show that gastric mucosal exposure to HCl and capsaicin is differentially transmitted to the brainstem and spinal cord. Since only HCl blocks gastric emptying, it is hypothesized that the two stimuli are transduced by different afferent pathways. We infer that HCl is exclusively signalled by gastric vagal afferents whereas capsaicin is processed both by gastric vagal and intestinal spinal afferents.
Holzer
Peter
P
Department of Experimental and Clinical Pharmacology, Medical University of Graz, Universitätsplatz 4, A-8010 Graz, Austria. peter.holzer@meduni-graz.at
Painsipp
Evelin
E
Schuligoi
Rufina
R
D000344:Afferent Pathways / Q000187:drug effects; D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology*; D002211:Capsaicin / Q000494:pharmacology*; D005260:Female; D005744:Gastric Acid / Q000502:physiology*; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*
D002211:Capsaicin