beta-endorphin and Edema

The non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used classes of drugs for the management of acute and chronic pain in dentistry. Their therapeutic efficacy and toxicity are well-documented and provide evidence that NSAIDs generally provide an acceptable therapeutic ratio of pain relief with fewer adverse effects than the opioid-mild analgesic combination drugs that they have largely replaced for most dental applications. The great many studies done with the oral surgery model of acute pain indicate that a single dose of an NSAID is more effective than combinations of aspirin or acetaminophen plus an opioid, with fewer side-effects, thus making it preferable for ambulatory patients. The combination of an NSAID with an opioid generally results in marginal analgesic activity but with an increased incidence of side-effects, which limits its use to patients in whom the NSAID alone results in inadequate analgesia. The selective COX-2 inhibitors hold promise for clinical efficacy with less toxicity from chronic administration and may prove advantageous for the relief of chronic orofacial pain. The use of repeated doses of NSAIDs for chronic orofacial pain should be re-evaluated in light of a lack of documented efficacy and the potential for serious gastrointestinal and renal toxicity with repeated dosing.

Topics: Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; beta-Endorphin; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Drug Combinations; Edema; Facial Pain; Humans; Isoenzymes; Ketorolac; Membrane Proteins; Periodontitis; Prostaglandin-Endoperoxide Synthases; Temporomandibular Joint Disorders; Toothache

It has been shown that inflammation of rat paws elicits accumulation of opioid peptide beta-endorphin-containing immune cells in the inflamed subcutaneous tissue, contributing to immunocyte-produced pain suppression. However, the possible mechanisms involved in the pharmacological application of beta-endorphin in rat paw inflammation have not been investigated. The present study was set up to explore the effects of intraplantar injection of beta-endorphin on Concanavalin A-induced paw edema in two inbred rat strains, Albino Oxford (AO) and Dark Agouti (DA). Both high dose-induced suppression and low dose-induced potentiation of edema development in AO and DA rats, respectively, were blocked with antagonists specific for delta (naltrindole) and kappa (nor-binaltorphimine) opioid receptors. beta-endorphin in vitro decreased phagocytosis and increased nitric oxide (NO) production in air pouch granulocytes obtained from AO rats. However, in cells from DA rat strain beta-endorphin modulated both phagocytosis and NO production in a concentration-dependent manner. It could be concluded that the strain-dependent opposing effects of beta-endorphin on paw inflammation are mediated through delta and kappa opioid receptors and probably involve changes in the production of reactive oxygen species by inflammatory cells. Our results point to the importance of genotype for pharmacological manipulations and the development of inflammation.

Topics: Animals; beta-Endorphin; Concanavalin A; Dose-Response Relationship, Drug; Edema; Female; Granulocytes; Hindlimb; Inflammation; Male; Naltrexone; Narcotic Antagonists; Neurotransmitter Agents; Nitric Oxide; Phagocytosis; Rats; Rats, Inbred Strains; Receptors, Opioid, delta; Receptors, Opioid, kappa; Species Specificity

This study investigates the role of the opiod receptors and of the opioid peptide beta-endorphin in the development of yeast-induced inflammation in the rat paw. Pretreatment with the opioid receptor antagonist naltrexone (10 mg/kg i.p.) exacerbates the paw edema, while morphine pretreatment (5 and 10 mg/kg) reduces it. In addition, the intravenous injection of a specific anti-beta-endorphin antibody aggravates the yeast-induced inflammation. On the contrary, both the kappa-opioid receptor antagonist MR 1452 (2.5, 5 and 10 mg/kg i.p.) and the delta-opioid receptor antagonist ICI 174-864 (2.5, 5 and 10 mg/kg i.p.) do not interfere with the inflammatory process. After intraplantar injection, naltrexone, morphine and the anti-beta-endorphin antibody do not interfere with the yeast-induced inflammatory edema. Our data suggest that beta-endorphin exerts an inhibitory regulation on the inflammatory responses through the activation of mu-opioid receptors probably located on immune cells, rather than in the paw.

Topics: Animals; Antibodies; Benzomorphans; beta-Endorphin; Edema; Enkephalin, Leucine; Foot; Inflammation; Male; Morphine; Naltrexone; Narcotic Antagonists; Rats; Rats, Sprague-Dawley; Receptors, Opioid; Yeasts

The acute effect of the non-tricyclic, pro-serotoninergic, antidepressant drug fluoxetine on inflammatory edema was evaluated in the rat. Fluoxetine significantly and dose dependently reduced the swelling induced by the injection of 10% brewer's yeast suspension in the hindpaw. Both adrenalectomy and hypophysectomy prevented the effect of fluoxetine. In contrast pretreatment with the corticotropin-releasing hormone antagonist alpha-helical CRH-(9-41) did not interfere with the anti-inflammatory action of fluoxetine. Moreover, the drug induced a significant increase of corticosterone plasma concentrations in vivo, whereas, in vitro, it did not stimulate beta-endorphin release from anterior pituitary cells. Our data suggest that fluoxetine exerts a potent anti-inflammatory action by inducing pituitary-adrenocortical activation via serotonin.

Topics: Adrenalectomy; Animals; beta-Endorphin; Corticosterone; Dose-Response Relationship, Drug; Edema; Fluoxetine; Hypophysectomy; Hypothalamo-Hypophyseal System; Inflammation; Male; Pituitary-Adrenal System; Rats; Rats, Sprague-Dawley

The effect of dextroamphetamine sulfate (Dexedrine) on plasma opioid peptides, hormones, and other metabolites was studied in eight female subjects with idiopathic (orthostatic) edema and five healthy females. All subjects were given 20 mg of dextroamphetamine sulfate, a drug widely used in the treatment of this disorder, and blood samples were collected before and 30, 60, and 90 minutes after treatment. Patients with idiopathic (orthostatic) edema had significantly lower plasma sodium levels but higher blood urea nitrogen, aldosterone, and renin levels. D-amphetamine decreased aldosterone and renin levels in both groups. Plasma adrenocorticotropin levels were lower whereas met-enkephalin levels were higher in idiopathic (orthostatic) edema subjects compared to control subjects. D-amphetamine had no significant effect on plasma beta-endorphin, adrenocorticotrophic hormone, or enkephalins. Our data indicate that opioid peptides, especially enkephalins, and adrenocorticotrophic hormone may be involved in the pathogenesis of idiopathic (orthostatic) edema syndrome, but they seem uninvolved in the aldosterone- and renin-lowering action of amphetamine. It is possible that amphetamine is acting further down the chain, either directly on the adrenal and kidney or the microvasculature, rather than at hypothalamus-pituitary axis.

Topics: Adrenocorticotropic Hormone; Adult; Aldosterone; beta-Endorphin; Blood Urea Nitrogen; Body Weight; Dextroamphetamine; Dopamine; Edema; Endorphins; Enkephalin, Leucine; Enkephalin, Methionine; Female; Humans; Hypotension, Orthostatic; Middle Aged; Renin; Sodium; Spironolactone; Syndrome; Vasopressins

This study was designed to characterize physiological events related to a single or repeated experimental anaphylactoid reactions (by Compound 48/80) in non-stressed or cold-restrained rats. Acute treatment with Compound 48/80 (1 mg/kg, i.p.) increases Beta-endorphin(ir) content in the neurointermediate lobe (NIL) of rat pituitary. Moreover, repeated treatment with Compound 48/80 showed tolerance effects. These animals, exposed to stressful conditions, exhibited a fully evident paw oedema following carrageenin oedema-test, whereas saline-pretreated rats, under the same experimental conditions, showed reduced local inflammation. Since Compound 48/80 produces characteristic, systemic, anaphylactoid reaction in the rat, with a very high degree of selectivity in its action, our results suggest that mast-cell histamine and Beta-endorphin from NIL pituitary are involved in the body's reactivity to stressful stimuli.

Topics: Animals; beta-Endorphin; Carrageenan; Cold Temperature; Edema; Histamine; Homeostasis; Male; Mast Cells; p-Methoxy-N-methylphenethylamine; Pituitary Gland; Rats; Rats, Inbred Strains; Restraint, Physical