Central, naloxone-reversible antinociception by diclofenac in the rat

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Abstract
The antinociceptive effect of subcutaneously (s. c.), intracerebroventricularly (i.c.v.) or intrathecally (i.t.) administered diclofenac was studied in a series of experiments employing the tail-flick (0.01–10.0 mg/kg body weight i. p., 1–50 μg i.c.v., 1–10 μg i.t.) and hotplate (0.01–50 mg/kg body weight i. p., 1– 50 μg i. c. v., 1–10 μg i. t.) models representing somatosensory stimuli and the writhing test (0.001 mg–10 mg s. c., 0.1–200 μg i.c.v., 0.1–100 μg i. t.) and colorectal distension (1–200 μg i.c.v.) models representing noxious visceral stimuli. Diclofenac did not exert any antinociceptive effects in the tail-flick or hot-plate models. In the writhing test, diclofenac dose-dependently inhibited the number of writhings after s. c. administration (0.001–10.0 mg/kg body weight) with an ED50 of 1 mg/kg. A similar dose-dependent action of diclofenac was seen after i.c.v. (0.1–200 μg) and i.t. (0.1–100 μg) administration with an ED50 of 3 α in both cases. The antinociceptive effect of diclofenac administered s. c., i.c.v. or i.t. was almost completely reversed by pretreatment with naloxone, (1 mg/kg body weight s. c.). In the colorectal distension model, the i.c.v. administration of diclofenac (1–200 μg), which attenuated the cardiovascular response to colorectal distension, was reversed by naloxone. The pressor and tachycardia response to a 20 s, 80 mmHg colorectal distension was inhibited by diclofenac 100 μg i.c.v. (16.1 ± 1.7 mmHg or 58% and 39.4 ± 0.4 bpm or 70% versus control, respectively). It is concluded that diclofenac exerts a central, naloxone-reversible antinociceptive action in experimental animals after noxious visceral stimuli but not after somatosensory stimuli.

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