Calotropis procera latex-induced inflammatory hyperalgesia--effect of antiinflammatory drugs

Abstract

The milky white latex of plant Calotropis procera produces inflammation of the skin and mucous membranes on accidental exposure. It produces edema on local administration due to the release of histamine and prostaglandins and is associated with hyperalgesia. In the present study we have evaluated the antiedematous and analgesic activity of antiinflammatory drugs against inflammatory response induced by dried latex (DL) of C procera in rat paw edema model. An aqueous extract of DL of C procera was injected into the subplantar surface of the rat paw and the paw volume was measured by a plethysmometer at 0, 1, 2, 6, 12, and 24 hours. Concomitantly the hyperalgesic response was also evaluated by motility test, stair climbing ability test, dorsal flexion pain test, compression test, and observing the grooming behavior. The inhibitory effect of diclofenac and rofecoxib on edema formation and hyperalgesic response was compared with cyproheptadine (CPH). DL-induced edema formation was maximum at 2 hours that was associated with decreased pain threshold, functional impairment, and grooming. Treatment with antiinflammatory drugs and CPH significantly attenuated the edematous response and grooming, increased the pain threshold, and improved functional parameters. Both antiinflammatory and antiserotonergic drugs significantly inhibited the hyperalgesia associated with DL-induced paw edema. Rofecoxib was found to be superior than diclofenac and was as effective as CPH in ameliorating the hyperalgesia. However, it was found to be less effective than CPH in attenuating edema formation.

Figure 1

Time course for DL-induced edema formation and extent of compression required to elicit pain in rat paw. Aqueous solution of DL of C procera (0.1 mL of 1% solution) and NS (0.1 mL) were injected into the subplantar surface of the rat paw and edema volume and compression were measured at 1, 2, 6, 12, and 24 hours (n = 6). Bars indicate edema volume and lines indicate compression to elicit pain.

Figure 2

Antiinflammatory effect of various drugs on DL-induced paw edema. Edema was induced by injecting 0.1 mL of 1% solution of DL into subplantar surface of right hind paw. The drugs were administered orally 1 hour before injecting DL. Edema volume was measured at 2 hours (n = 6). CPH 10-cyproheptadine 10 mg/kg; Diclo 10-diclofenac 10 mg/kg; Diclo 100-diclofenac 100 mg/kg; Rofe 15-rofecoxib 15 mg/kg; Rofe 100-rofecoxib 100 mg/kg; ^∗P < .01 and ^∗∗P < .05 versus DL control.

Figure 3

Antihyperalgesic effect of various drugs on DL-induced inflammatory hyperalgesia. Edema was induced by injecting 0.1 mL of 1% solution of DL into subplantar surface of right hind paw. The drugs were administered orally 1 hour before injecting DL. Dorsal flexion pain score was recorded at 1, 2, 6, 12, and 24 hours (n = 6). The data is illustrated as box plots where bold line represents median values, boxes represent interquartile ranges (25th and 75th percentiles), and whiskers represent extreme values.

Figure 4

Effect of various drugs on DL-induced motility impairment and staircase climbing ability (SCA). Edema was induced by injecting 0.1 mL of 1% solution of DL into subplantar surface of right hind paw. The drugs were administered orally 1 hour before injecting DL. Motility and staircase climbing ability were observed at 2 hours (n = 6). ^∗P < .01 versus DL control.