oxytocin and Edema

Our previous study verified a sex difference of anti-hyperalgesia in rats and anti-allodynia in mice induced by intrathecal oxytocin (OT). In the model of intraplantar carrageenan-induced inflammatory hyperalgesia, intrathecal OT injection induced a substantial anti-hyperalgesia in male rats even at a low dose (0.125 nmol). In contrast, female rats only responded to an extremely high dose (1.25 nmol). This sex difference concurs with a lower expression of OT receptors and higher expression of insulin-regulated aminopeptidase (IRAP; OT degrading enzyme) in the spinal cords of female rats. In this study, we further determined the role of female hormones in this sex difference by using ovariectomized rats. Our results show that a low dose of intrathecal OT caused a significant anti-hyperalgesia effect in ovariectomized female rats, similar to that seen in male rats. Ovariectomy did not cause any change of paw edema except at the late stage of convalescence when compared with the sham-operated group. Ovariectomy-induced faster recovery from edema but did not affect the severity of hyperalgesia. Moreover, there was a similar amount of IRAP expression in ovariectomized and sham rats. When estradiol (E2) was given together with OT, OT-induced anti-hyperalgesia was abolished at the developmental stage of hyperalgesia in ovariectomized rats. These results show an inhibitory role of female hormones generated from ovaries (mainly estrogen) in the sex difference of anti-hyperalgesia induced by OT. This study suggests the feasibility of a novel OT-based remedy to treat hyperalgesia in men and in menopausal women no receiving hormonal supplements.

Topics: Animals; Edema; Estrogens; Female; Humans; Hyperalgesia; Male; Mice; Ovariectomy; Oxytocin; Rats; Rats, Sprague-Dawley; Spinal Cord

Previously, we demonstrated intrathecal administration of oxytocin strongly induced anti-hyperalgesia in male rats. By using an oxytocin-receptor antagonist (atosiban), the descending oxytocinergic pathway was found to regulate inflammatory hyperalgesia in our previous study using male rats. The activity of this neural pathway is elevated during hyperalgesia, but whether this effect differs in a sex-dependent manner remains unknown. We conducted plantar tests on adult male and female virgin rats in which paw inflammation was induced using carrageenan. Exogenous (i.t.) application of oxytocin exerted no anti-hyperalgesic effect in female rats, except at an extremely high dose. Female rats exhibited similar extent of hyperalgesia to male rats did when the animals received the same dose of carrageenan. When atosiban was administered alone, the severity of hyperalgesia was not increased in female rats. Moreover, insulin-regulated aminopeptidase (IRAP) was expressed at higher levels in the spinal cords of female rats compared with those of male rats. Oxytocin-induced anti-hyperalgesia exhibits a sex-dependent difference in rats. This difference can partially result from the higher expression of IRAP in the spinal cords of female rats, because IRAP functions as an enzyme that degrades oxytocin. Our study confirms the existence of a sex difference in oxytocin-induced anti-hyperalgesia at the spinal level in rats.

Topics: Animals; Blotting, Western; Carrageenan; Cystinyl Aminopeptidase; Edema; Female; Hyperalgesia; Inflammation; Injections, Spinal; Lumbar Vertebrae; Male; Oxytocin; Paraventricular Hypothalamic Nucleus; Rats, Sprague-Dawley; Sex Characteristics; Spinal Cord

In our previous study, we showed that intrathecal (i.t.) administration of angiotensin IV (Ang IV), an insulin-regulated aminopeptidase (IRAP) inhibitor, attenuated inflammatory hyperalgesia in rats. Using the plantar test in rats with carrageenan-induced paw inflammation, we investigated the possible mechanism(s) of this effect. Because i.t. oxytocin was reported to produce a dose-dependent anti-hyperalgesia in rats with inflammation, we speculate that there is a possible correlation between oxytocin-induced and Ang IV-induced anti-hyperalgesia. Using i.t. co-administered atosiban (oxytocin receptor antagonist), the anti-hyperalgesia by Ang IV was completely abolished. This indicated that oxytocin could be the major IRAP substrate responsible for the anti-hyperalgesia by Ang IV. When Ang IV was co-administered with a low dose of oxytocin, there was a significant enhancing effect of Ang IV on oxytocin-induced anti-hyperalgesia. In recent reports, electrical stimulation on the paraventricular hypothalamic nucleus (PVN) was proved to increase oxytocin release at the spinal cord. Our results also showed that Ang IV could prolong the anti-hyperalgesia induced by PVN stimulation. This suggests a possible protective effect of Ang IV on endogenous oxytocin degradation/dysfunctioning. Moreover, we examined the local effect of intraplantarly injected Ang IV in the same model. Our results showed no effect of local Ang IV on hyperalgesia and paw edema, indicating that Ang IV may not regulate the peripheral inflammatory process. Overall, our study suggests that Ang IV may act through the inhibition of the activity of IRAP to reduce the degradation of oxytocin at the spinal cord, thereby leading to anti-hyperalgesia in rats with inflammation.

Topics: Angiotensin II; Animals; Carrageenan; Cystinyl Aminopeptidase; Edema; Electric Stimulation; Foot; Hyperalgesia; Injections, Spinal; Male; Oxytocin; Paraventricular Hypothalamic Nucleus; Rats; Rats, Sprague-Dawley; Receptors, Oxytocin; Spinal Cord; Vasotocin

The Chinese herbs of myrrh and frankincense are often combined for treating some inflammatory pain diseases with synergistic therapeutic effects. In this study, we investigated the effects of individual herbal extracts and combined extract on anti-inflammatory and analgesic activities in vivo and analyzed the potential bioactive components from the combination extract by ultra-performance liquid chromatography coupled with mass spectrum (UPLC-MS/MS).. The anti-inflammatory activities were investigated by utilizing the paw edema mice induced by formalin and carrageenan. In addition, we determined the levels of PGE(2) and nitrite in the edema paw. The analgesic activity was examined against oxytocin-induced dysmenorrhea in mice. The effects of the administration of dolantin or indomethacin were also studied for references. The components in combination extract (CWE) were analyzed by UPLC-MS/MS.. The results showed that myrrh water extract (MWE) and the combined extract (CWE) at the 3.9 g/kg, and 5.2 g/kg showed inhibition of formalin-induced paw edema with inhibition rate of 30.44%, and 23.50%, respectively. The PGE(2) production was inhibited significantly by all samples (P<0.01 or P<0.05). CWE showed stronger suppression on carrageenan-induced mice paw edema at 2 and 3h after administration of drugs. The inhibitory effect of CWE on nitrite production was between that of MWE and water extract of frankincense (FWE) at 5.2 g/kg. The dysmenorrhea mice test showed MWE could remarkably reduce the writhing times (P<0.05) and prolong the latency period, while FWE showed no obvious effects on the writhing times. CWE significantly reduced the writhing times and prolong the latency period (P<0.01).. These results demonstrated MWE, FWE, and CWE exhibited significant anti-inflammatory and analgesic activities. The findings suggest that CWE may be therapeutically more useful for mitigating inflammatory pain than individual herbal extract. In addition, 12 potential active compounds were identified from CWE. These data may support the fact the traditional application of this combined extract in treating various diseases associated with inflammatory pain.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Boswellia; Carrageenan; Chromatography, Liquid; Commiphora; Dinoprostone; Disease Models, Animal; Drug Combinations; Dysmenorrhea; Edema; Female; Formaldehyde; Indomethacin; Meperidine; Mice; Mice, Inbred ICR; Molecular Structure; Motor Activity; Nitrites; Oxytocin; Pain Measurement; Pain Threshold; Plant Extracts; Plants, Medicinal; Reaction Time; Tandem Mass Spectrometry; Time Factors

The neuropeptide oxytocin (OXT) contributes to the regulation of diverse cognitive and physiological functions including nociception. Indeed, OXT has been reported to be analgesic when administered directly into the brain, the spinal cord, or systemically. Although many authors have reported the analgesic effects of OXT, its mechanism has not been well elucidated. Recently, it has been also hypothesize that OXT, increasing intracellular concentration of calcium, could regulate the production of mediators, like endocannabinoids (eCB). It has been well documented that eCB are able to suppress pain pathways. The present study investigates the effect of OXT in paw carrageenan-induced pain. Intracerebroventricular (icv) administration of OXT, but neither intraperitoneal nor intraplantar route, induces an antihyperalgesic effect increasing paw withdrawal latency to mechanical or thermal stimuli. Our results clearly demonstrate that 3 and 6h following carrageenan challenge, central administration of OXT (30 ng/mouse) shows a significant antihyperalgesic activity. Moreover, for the first time, we demonstrate that CB1 receptor plays a key role in the antihyperalgesic effect of OXT. In fact our results show CB1 antagonist, but not the specific CB2 antagonist reduce OXT-induced antihyperalgesic effect. In addition, our data show that central OXT administration is able to reduce carrageenan-induced hyperalgesia but does not modify carrageenan-induced paw edema. Finally, using opioid antagonists we confirm an important role of opioid receptors. In conclusion, our experiments suggest that central administration of OXT reduces hyperalgesia induced by intraplantar injection of carrageenan, and this effect may work via cannabinoid and opioid systems.

Topics: Analgesics, Non-Narcotic; Animals; Carrageenan; Cyclooxygenase 2; Dose-Response Relationship, Drug; Edema; Hyperalgesia; Injections, Intraventricular; Male; Mice; Motor Activity; Naloxone; Narcotic Antagonists; Nitric Oxide Synthase Type I; Nitric Oxide Synthase Type II; Oxytocin; Pain; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Receptors, Opioid; Receptors, Oxytocin; Spinal Cord

The latex of the wild growing plant Calotropis procera produces inflammation of the skin and mucous membranes upon accidental exposure. On local administration it elicits an intense inflammatory response due to the release of histamine and prostaglandins that is associated with hyperalgesia. In the present study we have evaluated the anti-inflammatory and antinociceptive activity of oxytocin and melatonin against rat paw edema induced by dried latex (DL) of C procera and compared it with that against carrageenan-induced paw edema. Aqueous extract of DL of C procera or carrageenan (1%) was injected into the subplantar surface of the rat paw and the paw volume was measured at 0, 1, 2, 3, 4, 6, 10, and 24 hours. The associated hyperalgesic response and functional impairment were also evaluated concomitantly by dorsal flexion pain test, motility test, and stair climbing ability test. The inhibitory effect of oxytocin and melatonin on edema formation and hyperalgesic response was compared with dexamethasone. DL-induced edema formation was maximum at 2 hours and was associated with decreased pain threshold and functional impairment. Treatment with melatonin significantly attenuated the edematous response while both oxytocin and melatonin increased the pain threshold and improved functional parameters. Both oxytocin and melatonin significantly inhibited the hyperalgesia associated with DL-induced paw edema. Oxytocin was found to be as effective as melatonin in ameliorating the hyperalgesic response. However, it was found to be less effective than melatonin in attenuating edema formation.

Topics: Analgesics; Animals; Calotropis; Carrageenan; Edema; Hyperalgesia; Latex; Latex Hypersensitivity; Male; Melatonin; Motor Activity; Oxytocin; Pain Measurement; Pain Threshold; Rats; Rats, Wistar

The effects of oxytocin on carrageenan-induced inflammation in rat hindpaw was examined. Oxytocin at 100 (P < 0.05) and 1000 microg/kg s.c. (P < 0.05), but not at 1 and 10 microg/kg s.c., reduced the edema of the paw when measured up to 10 h after the injection. An additional experiment showed that the effect was comparable to the effect of the glucocorticoid dexamethasone. No effect was found by oxytocin i.c.v. In addition, rats with carrageenan-induced inflammation given oxytocin (1000 microg/kg s.c.) responded differently to nociceptive mechanical stimulation (P < 0.05) and had a reduced amount of myeloperoxidase (marker for neutrophil recruitment) in the paw (P < 0.01).

Topics: Animals; Biomarkers; Brain; Carrageenan; Dexamethasone; Dose-Response Relationship, Drug; Drug Interactions; Edema; Hindlimb; Hormone Antagonists; Inflammation; Injections, Intramuscular; Injections, Intraventricular; Injections, Subcutaneous; Male; Oxytocin; Pain Threshold; Peroxidase; Physical Stimulation; Rats; Rats, Sprague-Dawley; Time Factors; Vasotocin

An adult golden-mantled flying fox (Pteropus pumilus) was diagnosed with nephrotic syndrome on the basis of the findings of proteinuria, hypoalbuminemia, hypercholesterolemia, and cranial edema. Membranoproliferative glomerulitis and interstitial nephritis were confirmed antemortem by renal biopsy. The bat had received seven injections of oxytocin in the period immediately prior to presentation. The possible role of oxytocin in the development of the nephropathy is discussed. Supportive care and treatment with a single plasma transfusion, furosemide, and prednisone led to a gradual but complete resolution of the nephrotic syndrome in this animal.

Topics: Animals; Blood Chemical Analysis; Blood Transfusion; Chiroptera; Diagnosis, Differential; Diuretics; Edema; Female; Furosemide; Glucocorticoids; Hematologic Tests; Kidney; Liver; Nephrotic Syndrome; Oxytocin; Prednisone; Skull

The essential oil of Bupleurum gibraltaricum showed considerable anti-inflammatory activity against carrageenan-produced pedal edema in rats. This appeared to be due to the delta-3-carene component. The essential oil and delta-3-carene both produced qualitatively similar changes in rat uterine contractions caused by oxytocin (a progressive dose-related modification of the concentration-response curves) and acetylcholine (non-progressive modification of the concentration-response curves).

Topics: Acetylcholine; Animals; Anti-Inflammatory Agents, Non-Steroidal; Bicyclic Monoterpenes; Edema; Female; In Vitro Techniques; Indomethacin; Monoterpenes; Oxytocin; Plant Oils; Plants, Medicinal; Rats; Rats, Inbred Strains; Terpenes; Uterine Contraction

Topics: Apgar Score; Edema; Embryonic and Fetal Development; Female; Humans; In Vitro Techniques; Norepinephrine; Oxytocin; Placenta; Pregnancy; Pregnancy Complications; Vasoconstriction

Bradykinin (BK) produced a dose-related increase in the paw volume of the rat. Responses to BK at all doses used were not affected by pretreating the rats with diphenhydramine, 1 mg kg-1, or indomethacin, 2.5 and 5 mg kg-1. Indomethacin, 10 mg kg-1 produced a small but significant reduction in the responses to BK. Captopril 1 mg kg-1 enhanced responses to low but not to high doses of BK. The rank order of potency of various kinin analogues to increase paw volume was found to be methionyl-lysyl-BK (met-lys-BK) greater than BK greater than lysyl-BK (Kallidin) much greater than des-Arg9-BK. The B1-receptor antagonist des-Arg9-Leu8-BK did not affect responses to BK on paw volume. Two modified kinin fragments S2302 (H-D-Pro-Phe-Arg-p-Nitroaniline) and S2441 (H-D-Pro-Phe-Arg-NH-heptyl) produced dose-related increases in paw volume both having approximately half the potency of BK. These responses were not antagonised by diphenhydramine, 1 mg kg-1 which reduced significantly the response to histamine. On the isolated rat uterus the rank order of potency of various kinins was BK greater than Kallidin greater than met-lys-BK greater than des-Arg9-BK. The two modified kinin fragments S2302 and S2441 (but not des-Arg9-Leu8-BK) antagonised BK induced contractions of the rat uterus. From the rank order of potency studies the receptor mediating contraction of the rat uterus in vitro and increase in rat paw volume to BK appear to be of the same type.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Bradykinin; Dinoprost; Edema; Female; Foot; In Vitro Techniques; Kallidin; Kinins; Male; Oxytocin; Prostaglandins F; Rats; Rats, Inbred Strains; Uterine Contraction; Uterus

Mammary blood flow (MBF) and mammary plasma flow (MPF) were measured by an antipyrine absorption method in 8 cows affected with udder edema and 3 healthy (control) cows at least 2 weeks before parturition, at parturition, and 2 weeks after parturition. Cows with udder edema had a significant decrease in MBF at calving compared with the control cows (P less than or equal to 0.05), whereas there was no significant difference (P greater than 0.05) in MBF between affected and control groups 2 weeks before or 2 weeks after parturition. Cows with udder edema also had a decrease in MPF at parturition that was not statistically significant (P greater than 0.05) when compared with that in the control cows.

Topics: Animals; Cattle; Cattle Diseases; Dexamethasone; Dogs; Edema; Epinephrine; Female; Labor, Obstetric; Mammary Glands, Animal; Oxytocin; Pregnancy; Regional Blood Flow

Topics: Adult; Albuminuria; Edema; Female; Furosemide; Humans; Hypertension; Movement Disorders; Obstetric Labor Complications; Oxytocin; Potassium; Pre-Eclampsia; Pregnancy; Uterine Diseases; Uterine Inertia; Water-Electrolyte Balance

Topics: Abortion, Induced; Adolescent; Adult; Brain Edema; Edema; Female; Humans; Hypotonic Solutions; Oxytocin; Seizures; Sodium Chloride; Water Intoxication

Topics: Administration, Oral; Adult; Diplopia; Edema; Eye Manifestations; Female; Humans; Injections, Intravenous; Labor, Obstetric; Oxytocin; Pregnancy

Topics: 1-Propanol; Animals; Anti-Inflammatory Agents; Bradykinin; Edema; Granuloma; Muscle Contraction; Oxytocin; Piperidines; Rats

Topics: Amniotic Fluid; Antigens; Blood Transfusion, Intrauterine; Cesarean Section; Digoxin; Edema; Erythroblastosis, Fetal; Female; Humans; Hydrochlorothiazide; Immunization; Infant, Newborn; Infant, Premature; Oxytocin; Plasmapheresis; Pregnancy; Rh-Hr Blood-Group System

Topics: Adult; Edema; Female; Headache; Humans; Injections; Methods; Oxytocin; Postpartum Hemorrhage; Pregnancy

Topics: Adult; Diet Therapy; Edema; Female; Glucose Tolerance Test; Humans; Hyperinsulinism; Male; Methylphenidate; Multiple Sclerosis; Oxytocin; Phenformin; Phenytoin

Topics: Adult; Anuria; Diuresis; Edema; Female; Humans; In Vitro Techniques; Oxytocin

Topics: Dihydroergotoxine; Dystocia; Edema; Ergot Alkaloids; Female; Humans; Oxytocics; Oxytocin; Pre-Eclampsia; Pregnancy; Secale; Spasm; Toxemia; Uterus

Topics: Animals; Edema; Kidney; Oxytocin; Rats; Renal Elimination