In the present study, the effect of chronic oral administration of curcumin in the presence or absence of morphine and noloxone was investigated on the visceral nociception induced by acetic acid in rats. Intraperitoneal injection of acetic acid (1 mL, 2%) produced contractions in the abdominal musculature (writhes). The latency time to the beginning of the first writhe was measured and the total number of writhes in the 1 h after acetic acid injection was counted. The latency time to the beginning of the first writhe was significantly (p < 0.05) increased and the number of writhes was significantly (p < 0.05) decreased by curcumin (20 and 40 mg kg(-1) body weight). The same results were obtained after subcutaneous injection of morphine (1 mg kg(-1) b.wt.). Naloxone at the dose of 1 mg kg(-1) body weight had no effect on pain intensity. Curcumin significantly (p < 0.05) enhanced the effect of morphine on the visceral pain responses, however did not reverse the effect of naloxone. Present data suggest that in the acetic acid-induced visceral nociception of rats, curcumin may produce an antinociceptive effect and the endogenous analgesic opioid system is involved in the curcumin-induced antinociception.

The results of the present study showed pain suppressing effects for histamine. Histamine H2 and H3, and to a lesser extent, H1 receptors might be involved in histamine-induced antinociception. Opioid receptors might be involved in suppressive effects of histamine and thioperamide.

In this study, the effects of intraperitoneal (i.p.) injection of crocin in the absence and presence of subcutaneous (s.c.) injections of morphine and naloxone were investigated on the formalin test in rats. The formalin test was induced by intra-plantar (i.pl.) injection of formalin (50 microL, 1%), and the time spent licking and biting of the injected paw was measured for 1 h. Formalin induced a marked biphasic (first phase: 0-5 min and second phase: 15-45 min) pain response. Morphine (1 mg/kg, s.c.) significantly (p < 0.05) suppressed both phases of pain. Naloxone (2 mg/kg, s.c.) alone did not change the intensity of pain, but pretreatment with naloxone (2 mg/kg) significantly (p < 0.05) prevented morphine (1 mg/kg)-induced antinociception. Crocin at doses of 50, 100 and 200 mg/kg significantly (p < 0.05) attenuated pain. Crocin (100 mg/kg, i.p.) significantly (p < 0.05) increased the morphine (1 mg/kg, s.c.)-induced antinociception. Naloxone (2 mg/kg) did not reverse the suppressive effect of crocin (100 mg/kg) on pain. Crocin at a dose of 400 mg/kg significantly (p < 0.05) suppressed locomotor activities. These findings indicate that morphine through a naloxone-sensitive mechanism produced analgesia. Crocin produced a dose-dependent antinociceptive effect. In addition, crocin increased morphine-induced antinociception, but naloxone did not change the antinociceptive effect of crocin.

In this study, the effect of curcumin on the formalin-induced pain was investigated in rats. Interaction between curcumin and opioid system using morphine and naloxone was also examined. A biphasic pain response was induced after intraplantar injection of formalin (50 microL, 1%). Curcumin, morphin and naloxone had no effect on the early phase of pain. Late phase of pain was suppressed by curcumin at the doses of 100 and 200 mg kg(-1) body weigh. Morphine (1 mg kg(-1) BW) reduced, whereas naloxone (1 mg kg(-1) BW) did not affect the late phase of pain. Currcumin did not influence the morphine-induced antinociception, but reversed the effect of naloxone on pain. Present findings indicate that curcumin may produce antinociception by activation of both opioid and non opioid mechanisms of pain.

In this study, the effects of intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) injection of crocin in separate and combined treatments with i.p. injections of morphine (an opioid receptor agonist) and naloxone (an opioid receptor antagonist) were investigated on acute corneal pain in rats. Acute corneal pain was induced by local application of a drop of 5 M NaCl solution on the corneal surface. The number of eye wipes was taken as a pain response, and counted during the first 30 s. Crocin injected i.p. and i.c.v. and morphine injected i.p. significantly (p < 0.05) decreased the number of eye wipes. Morphine (i.p.)-induced antinociception was significantly (p < 0.05) increased by the systemically and centrally injected crocin. The antinociceptive effects induced by i.p. and i.c.v. injections of crocin were not reversed by i.p. injection of naloxone. These findings indicated that both crocin and morphine attenuated hypertonic saline-induced corneal pain. The opioid receptors may not be involved in the analgesic mechanism of crocin.