A comparison of the anti-inflammatory and anti-nociceptive activity of nitroaspirin and aspirin

Abstract

1. Nitroaspirin (2.5 - 50 mg kg(-1), i.p. or 2.5 - 100 mg kg(-1), p.o.) and aspirin (2.5 - 100 mg kg(-1), i.p. or p.o.) exhibit anti-inflammatory activity in the carrageenan-induced hindpaw oedema model in the rat. When administered i.p., nitroaspirin was a more effective anti-oedema agent than aspirin particularly in the 'early' phase (i.e. up to 60 min) of the response. The ED(50) values for nitroaspirin and aspirin as inhibitors of the 'late' phase response (measured at 180 min) were 64.3 micromol kg(-1) and >555 micromol kg(-1), respectively. When administered p.o., neither nitroaspirin nor aspirin exhibited significant anti-inflammatory activity in the 'early' phase and were of similar potency in the 'late' phase. Thus, at the highest dose used (100 mg kg(-1), 360 min) orally administered nitroaspirin (aspirin in parenthesis) inhibited oedema formation by 46.9+/-1.6% (47.2+/-3.8%, both n=6, P<0.05). 2. Nitroaspirin and aspirin (25 - 200 mg kg(-1), p.o.) caused dose-related inhibition of the hyperalgesia to mechanical stimulation following intraplantar injection of carrageenan in the rat. ED(50) values were 365 micromol kg(-1) and 784 micromol kg(-1), respectively. Neither drug influenced the threshold for mechanical stimulation in the contralateral (i.e. untreated) hindpaw. 3. Nitroaspirin and aspirin (2.5 - 100 mg kg(-1), p.o.) caused dose-related inhibition of acetic acid induced abdominal constrictions in the mouse (ED(50) values of 154.7 micromol kg(-1) and 242.8 micromol kg(-1), respectively). 4. Nitroaspirin and aspirin (>200 mg kg(-1), p.o.) reduced the 'late' phase (but not the 'early' phase) of the formalin-induced hindpaw licking assay in the mouse. Similarly, nitroaspirin and aspirin (>50 mg kg(-1), p.o.) prolonged tail withdrawal latency following application of a noxious heat stimulus in the mouse.

Figure 1

Effect of nitroaspirin (A) and aspirin (B) administered i.p. on carrageenan-induced hindpaw oedema formation in the rat. Results show increase in hindpaw volume (ml) and are mean±s.e.mean, n=6, ^*P<0.05 (ANOVA plus post-hoc Dunnett's test). Where no error bars are shown error lies within the dimensions of the symbol.

Figure 2

Effect of nitroaspirin (A) and aspirin (B) administered p.o. on carrageenan-induced hindpaw oedema formation in the rat. Results show increase in hindpaw volume (ml) and are mean±s.e.mean, n=6, ^*P<0.05 (ANOVA plus post-hoc Dunnett's test).

Figure 3

Effect of nitroaspirin (A) and aspirin (B) administered p.o. on carrageenan-induced mechanical hyperalgesia in the rat. Results show change (i.e. ‘post–pre') in nociceptive threshold (arbitrary units) to a noxious mechanical stimulus before and at 180 min after intraplantar injection of carrageenan. Drugs (mg kg⁻¹) were administered 150 min after carrageenan injection. Results show mean±s.e.mean, n=6, ^*P<0.05 (ANOVA plus post-hoc Dunnett's test).

Figure 4

Effect of nitroaspirin (A) and aspirin (B) on mouse formalin-induced hindpaw licking behaviour in the ‘early' (0–5 min after intraplantar formalin injection) and ‘late' phases (15–30 min). Figures at the foot of each pair of columns indicate dose of drug administered p.o. (mg kg⁻¹). Results shown mean±s.e.mean, n=3–20, ^*P<0.05 by ANOVA and post-hoc Dunnett's test.

Figure 5

Effect of nitroaspirin (A) and aspirin (B) on tail withdrawal latency to a noxious thermal stimulus in the mouse. Results show tail withdrawal latency (s) 30 min after p.o. administration of drug. Figures at the base of each column indicate dose administered (mg kg⁻¹, p.o.). Results show mean±s.e.mean, n=10, ^*P<0.05 (ANOVA plus post-hoc Dunnett's test).

Figure 6

Effect of nitroaspirin (A) and aspirin (B) on acetic acid induced abdominal constrictions in the mouse. Results show number of abdominal constrictions over a 30 min period following i.p. acetic acid injection. Drugs were administered p.o. 15 min prior to acetic acid injection. Figures at the base of each column indicate dose administered (mg kg⁻¹, p.o.). Results show mean±s.e. mean, n=10, ^*P<0.05 (ANOVA plus post-hoc Dunnett's test).

Figure 7

Effect of nitroaspirin and aspirin (both 50 mg kg⁻¹, p.o.) on acetic acid induced abdominal constrictions in the mouse. Results show number of abdominal constrictions over a 30 min period following i.p. acetic acid injection. Drugs were administered p.o. either 15, 180 or 360 min prior to acetic acid injection. Results show mean±s.e.mean, n=6, ^*P<0.05 (ANOVA plus post-hoc Dunnett's test).