Substance P potentiates the algogenic effects of intraarterial infusion of adenosine.
OBJECTIVE
This study investigated whether substance P potentiates the muscular and cardiac pain caused by the intraarterial infusion of adenosine, an autocoid known to induce muscular and cardiac ischemic-like pain in humans.


BACKGROUND
Substance P is involved in the generation of neurogenic inflammation and causes cutaneous hyperalgesia. Because substance P is present in perivascular nerves it might also cause muscular and cardiac hyperalgesia. To test this hypothesis its effects on adenosine-induced muscular and cardiac pain were investigated in humans.


METHODS
A randomized, crossover study of the algogenic effects of the intrailiac infusion of increasing scalar doses (from 125 to 2,000 micrograms/min) of adenosine or substance P (11.2 pmol/min) for 3 min, followed by the simultaneous infusion of substance P plus the same doses of adenosine, was carried out in nine patients with no evidence of peripheral vascular disease. A similar protocol was carried out by infusing increasing scalar doses of adenosine (from 50 to 800 micrograms/min) or substance P (11.2 pmol/min) for 3 min, followed by the simultaneous infusion 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 experienced 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) and was greater (47 vs. 30 mm, p < 0.05) during the simultaneous infusion of substance P plus adenosine than during the infusion of adenosine. Similarly, during intracoronary infusion, all patients experienced chest 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 infusion of substance P plus adenosine than during infusion of adenosine. No patient exhibited electrocardiographic signs of ischemia.


CONCLUSIONS
Substance P does not cause muscular or cardiac pain, but it provokes muscular and cardiac hyperalgesia.
Gaspardone
A
A
Servizio Speciale di Diagnosi e Cura di Emodinamica, Università di Roma Tor Vergata, Italy.
Crea
F
F
Tomai
F
F
Iamele
M
M
Crossman
D C
DC
Pappagallo
M
M
Versaci
F
F
Chiariello
L
L
Gioffrè
P A
PA
D000241:Adenosine / Q000008:administration & dosage / Q000009:adverse effects*; D000328:Adult; D000368:Aged; D002637:Chest Pain / Q000139:chemically induced; D003331:Coronary Vessels; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007083:Iliac Artery; D007261:Infusions, Intra-Arterial; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000139:chemically induced*; D017288:Pain Threshold / Q000187:drug effects*; D013373:Substance P / Q000008:administration & dosage / Q000494:pharmacology*
D013373:Substance P; D000241:Adenosine