Indian red scorpion (Mesobuthus tamulus, MBT) venom is known to augment the cardiorespiratory reflexes elicited by phenylbiguanide (PBG) or phenyldiguanide (PDG) [1,2]. These chemicals mediate the action via 5-HT3 receptors on the vagal C-fibers. Similar to PBG/PDG, capsaicin (a TRPV1 agonist) also produces cardio-respiratory reflexes involving vagal C-fibers [3]. However, the effect of MBT venom on the capsaicin-induced responses is not known. Therefore, the present study was undertaken to ascertain whether MBT venom also augments the capsaicin-induced responses. Further, to delineate the underlying mechanisms. Animal experiments were performed after obtaining the approval from the Institutional Ethical Clearance Committee. Adult rats of Charles foster strain were used. They were anesthetized with urethane (1.5 g/kg, i.p). The trachea, jugular vein and femoral artery were cannulated. The ECG, respiratory excursions and blood pressure were recorded. At the end of each experiment, the pulmonary water content was determined by physical method. Both PBG (10µg/kg) and capsaicin (10µg/kg) produced bradycardia, apnea-bradypnea and hypotension. After exposure to MBT venom (100µg/kg) for 30 minutes, the responses induced by PBG as well as capsaicin were augmented. Pulmonary edema was seen in these animals. The augmentation of PBG-induced responses and pulmonary edema were blocked after pretreatment with prostaglandin synthase inhibitor (indomethacin, 10mg/kg); kinin synthase inhibitor (aprotinin, 6000 KIU) and guanylate cyclase inhibitor (methylene blue, 5mg/kg). The augmentation of capsaicin-induced responses was blocked in indomethacin pretreated animals only but not in aprotinin and methylene blue pretreated animals even though pulmonary edema was not seen in these groups. Elevation of the endogenous cGMP levels by phosphodiesterase-V inhibitor (sildenafil, 100µg/kg) augmented the PBG-induced responses but not the capsaicin-induced responses. Sildenafil pretreated animals exhibited pulmonary edema. The present results demonstrate that MBT venom also augments the capsaicin-induced responses similar to PBG but involves distinctly different mechanisms. The PBG-induced responses are augmented by pulmonary edema-dependent mechanisms involving prostaglandins, kinins and guanylate cyclase-cGMP pathway whereas the capsaicin-induced responses are independent of pulmonary edema and involve nociceptive action of prostaglandins. The present study substantiates the existence of functionally different types of vagal-afferents. Our results with indomethacin, also implicate the direct and indirect action of prostaglandins in mediating the C-fiber reflexes.