Biol. Pharm. Bull. 29(1) 82—85 (2006)

نویسندگان

  • Juliana Lemos MAIA
  • Juceni Pereira DAVID
  • Jorge Mauricio
چکیده

the patients often seek medical care. Ascending pathways in the spinal cord that relay nociceptive information from the periphery to supraspinal central nervous system sites has been studied as potential targets for disrupting pain processing and providing relief. Despite the considerable advances in knowledge regarding the basic mechanisms underlying visceral pain and visceral hyperalgesia, no new effective therapies for abdominal pain have been discovered. Tissue injury, inflammation, and algesic chemicals produce changes in the stimulus response, leading to either sensitisation or desensitization of peripheral sensory afferents. An enormous range of pharmacological agents and endogenous substances via numerous receptors influence the visceral afferents. These substances produce their effects on visceral afferents by sensitization, opening of ion channels or by altering the expression of mediators, channels, or receptors. In recent years, a central importance is given to capsaicin (vanilloid) receptor 1 (VR1, also called transient receptor potential V1, TRPV1) in the regulation of the activity of sensory afferent nerves. TRPV1 gene knock out mice are analgesic to a wide range of painful inflammatory states, suggesting that TRPV1 receptor antagonists may be effective in those pain states associated with tissue injury, and chemical exposure. Currently, inflammatory hyperalgesia is managed by NSAIDs (cyclo-oxygenase inhibitors) and opioids, although very effective against inflammatory hyperalgesia, both of these therapeutic classes possess significant limitations. Opioids induce constipation, and nausea, whereas NSAIDs possess significant side effects on the gastrointestinal, cardiovascular and renal systems. In the recent past, many novel structures derived from a number of natural sources have been examined for the development of drugs acting as agonists or antagonists at vanilloid receptors, which include compounds like polygodial, a full vanilloid agonist derived from marsh pepper; warburganal from the bark of warburgia trees; isovelleral with terpenoid structure isolated from fungi; scalaradial, an unsaturated dialdehyde isolated from sponges; and scutigeral, isolated from edible mushrooms. The natural triterpenic mixture aand b-amyrin, isolated from Protium heptaphyllum has recently been shown to exert gastroprotective effect against ethanolinduced lesions and an antinociceptive effect in the visceral model of nociception induced by capsaicin, possibly involving the capsaicin-sensitive sensory afferents. Chemically, the aand b-amyrin is a mixture of two triterpenes belonging to the ursane (a-amyrin) and oleanane (b-amyrin) series. Oleanolic acid is a pentacyclic triterpene that pertains to oleanane (b-amyrin) series (Fig. 1) and previous studies established its gastroand hepato-protective and anti-inflammatory effects. So far there have been no available reports that show the efficacy of oleanolic acid in animal models of nociception that would simulate visceral pain in humans. Intracolonic instillation of capsaicin or mustard oil is a valid model of acute visceral pain in the mouse that evokes 82 Vol. 29, No. 1 Biol. Pharm. Bull. 29(1) 82—85 (2006)

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تاریخ انتشار 2005