SUBSTANCE-P POTENTIATES THE ALGOGENIC EFFECTS OF INTRAARTERIAL INFUSION OF ADENOSINE

Objectives. This study investigated whether substance P potentiates th e muscular and cardiac pain caused by the intraarterial infusion of ad enosine, an autocoid known to induce muscular and cardiac ischemic-lik e pain in humans. Background. Substance P is involved in the generatio n of neurogenic inflammation and causes cutaneous hyperalgesia. Be cau se substance P is present in perivascular nerves it might also cause m uscular and cardiac hyperalgesia. To test this hypothesis its effects on adenosine induced muscular and cardiac pain were investigated in hu mans. Methods. A randomized, crossover study of the algogenic effects of the intrailiac infusion of increasing scalar doses (from 125 to 2,0 00 mu g/min) of adenosine or substance P (11.2 pmol/min) for 3 min, fo llowed by the simultaneous infusion of substance P plus the same doses of adenosine, was carried out in nine patients with no evidence of pe ripheral vascular disease. A similar protocol was carried out by infus ing increasing scalar doses of adenosine (from 50 to 800 mu g/min) or substance P (11.2 pmol/min) far 3 min, followed by the simultaneous in fusion of substance P plus the same doses of adenosine, into the left coronary artery of eight patients with angina. Pain severity, assessed by a visual analog scale, is presented as median. The remaining data are presented as mean value +/- 1 SD. Results. All patients experience d pain during both adenosine and substance P plus adenosine infusion; no patient experienced pain during the infusion of substance P alone. During intrailiac infusion, all patients experienced pain in the right leg that occurred earlier (207 +/- 152 vs. 321 +/- 154 s, p < 0.05) a nd was greater (47 vs. 30 mm, p < 0.05) during the simultaneous infusi on of substance P plus adenosine than during the infusion of adenosine . Similarly, during intracoronary infusion, all patients experienced c hest pain that occurred earlier (409 +/- 242 vs. 596 +/- 210 s, p < 0. 05) and was greater (51 vs. 33 mm, p < 0.05) during the simultaneous i nfusion of substance P plus adenosine than during infusion of adenosin e. No patient exhibited electrocardiographic signs of ischemia. Conclu sions. Substance P does not cause muscular or cardiac pain, but it pro vokes muscular and cardiac hyperalgesia.