Involvement of endogenous opioid peptides in the peripheral antinociceptive effect induced by the coffee specific diterpene kahweol.

BACKGROUND: Kahweol is a diterpene present in the oil derived from coffee beans. Although several pharmacological activities of kahweol are already well described in the literature, no study was done in order to assess the analgesic activity of this substance. Thus, the aim of this study was to investigate the possible peripheral antinociceptive effect of kahweol. Considering that the opioid peptides have been implicated in peripheral antinociception induced by non-opioidergic compounds, the present study also evaluated the endogenous opioids involvement in this effect. METHODS: The rat paw pressure test was used, and hyperalgesia was induced by intraplantar injection of prostaglandin E2 (2µg/paw). All drugs were administered subcutaneously in the hindpaws of male Wistar rats. The expression of ß-endorphin was examined by immunohistochemistry in the skin tissue samples of the plantar surface of rat right hindpaws. RESULTS: Intraplantar injection of kahweol (40 and 80µg) induced significant peripheral antinociception. The antinociceptive effect of kahweol was due to a local peripheral action because the higher dose (80µg/paw) did not produce any effect in the contralateral paw. The opioid receptor antagonist naloxone (50 and 100µg/paw) prevented action of kahweol (80µg/paw) and the aminopeptidases inhibitor bestatin (400µg/paw) potentiated the antinociceptive effect of kahweol (40µg/paw). Furthermore, kahweol treatment increased the intensity of ß-endorphin immunoreactivity in the epithelium of rat paws. CONCLUSIONS: The results discussed here provide evidence that kahweol treatment has peripheral antinociceptive effect and suggest that this effect is mediated by the release of endogenous opioids.

Evaluation of exercise and potassium chloride supplementation on blood pressure and nociceptive threshold in hypertensive rats.

Hypertensive subjects present an increased nociceptive threshold, and the lack or delay of pain perception may impede detection of angina and myocardial infarction. Nutritional interventions, like potassium chloride (KCl) diet supplementation, and exercises are common nonpharmacological indications for treating hypertension. Spontaneous hypertensive rats (SHR) and normotensive male Wistar rats were submitted to a combination of exercise and KCl diet supplementation. Exercise reduced the nociceptive threshold in SHR; however, this effect was inhibited by KCl supplementation. Exercise and KCl supplementation did not alter systolic blood pressure. Reduction of the nociceptive threshold by exercise may be important for the detection of angina and myocardial infarction in hypertensive individuals.