The aim of the present study was to evaluate the central antinociceptive effects of eugenol after intraperitoneal administration. Experiments were carried out using male Sprague-Dawley rats. Subcutaneous injection of 5% formalin-induced nociceptive behavioral responses was used as the pain model. Subcutaneous injection of 5% formalin significantly produced nociceptive responses by increasing the licking time during nociceptive behavior. Subsequent intraperitoneal injection of 100 mg/kg of eugenol led to a significant decrease in the licking time. However, low dose of eugenol (50 mg/kg) did not affect the nociceptive behavioral responses produced by subcutaneous injection of formalin. Intrathecal injection of 30 µg of naloxone, an opioid receptor antagonist, significantly blocked antinociceptive effects produced by intraperitoneal injection of eugenol. Neither intrathecal injection of methysergide (30 µg), a serotonin receptor antagonist nor phentolamine (30 µg), an α-adrenergic receptor antagonist influenced antinociceptive effects of eugenol, as compared to the vehicle treatment. These results suggest that central opioid pathway participates in mediating the antinociceptive effects of eugenol.
Eugenol ; Formaldehyde ; Humans ; Injections, Intraperitoneal ; Injections, Spinal ; Injections, Subcutaneous ; Male ; Methysergide ; Naloxone ; Negotiating ; Phentolamine ; Rats, Sprague-Dawley ; Receptors, Opioid ; Serotonin

In the present study, the antinociceptive profiles of Agrimonia pilosa Ledeb extract were examined in ICR mice. Agrimonia pilosa Ledeb extract administered orally (200 mg/kg) showed an antinociceptive effect as measured by the tail-flick and hot-plate tests. In addition, Agrimonia pilosa Ledeb extract attenuated the writhing numbers in the acetic acid-induced writhing test. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of substance P (0.7 microg) was diminished by Agrimonia pilosa Ledeb extract. Intraperitoneal (i.p.) pretreatment with yohimbine (alpha2-adrenergic receptor antagonist) attenuated antinociceptive effect induced by Agrimonia pilosa Ledeb extract in the writhing test. However, naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by Agrimonia pilosa Ledeb extract in the writhing test. Our results suggest that Agrimonia pilosa Ledeb extract shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of Agrimonia pilosa Ledeb extract may be mediated by alpha2-adrenergic receptor, but not opioidergic and serotonergic receptors.
Agrimonia ; Animals ; Methysergide ; Mice ; Mice, Inbred ICR ; Naloxone ; Reaction Time ; Substance P ; Yohimbine

In the present study, the antinociceptive profiles of hop extract were characterized in ICR mice. Hop extract administered orally (from 25 to 100 mg/kg) showed an antinociceptive effect in a dose-dependent manner as measured in the acetic acid-induced writhing test. Antinociceptive action of hop extract was maintained at least for 60 min. Moreover, cumulative response time of nociceptive behaviors induced with intraplantar formalin injection was reduced by hop extract treatment during the 2nd phases. Furthermore, the cumulative nociceptive response time for intrathecal injection of substance P (0.7 microg) or glutamate (20 microg) was diminished by hop extract. Intraperitoneal pretreatment with naloxone (an opioid receptor antagonist) attenuated antinociceptive effect induced by hop extract in the writhing test. However, methysergide (a 5-HT serotonergic receptor antagonist) or yohimbine (an alpha2-adrenergic receptor antagonist) did not affect antinociception induced by hop extract in the writhing test. Our results suggest that hop extract shows an antinociceptive property in various pain models. Furthermore, the antinociceptive effect of hop extract may be mediated by opioidergic receptors, but not serotonergic and alpha2-adrenergic receptors.
Animals ; Formaldehyde ; Glutamic Acid ; Humulus ; Injections, Spinal ; Methysergide ; Mice ; Mice, Inbred ICR ; Naloxone ; Reaction Time ; Receptors, Opioid ; Serotonin ; Substance P ; Yohimbine

A number of studies have demonstrated that 5-hydroxytryptamine (5-HT) can induce muscle contraction or relaxation response and enhance secretion in the gastrointestinal tract via a multiplicity of 5-HT receptor subtypes. In the present study, we investigated the pharmacological characterization of the 5-HT-induced contractile response in longitudinal smooth muscle isolated from the feline ileum. Addition of 5-HT into muscle chambers enhanced the basal tone and spontaneous activity in a concentration-dependent manner. The neurotoxin tetrodotoxin did not alter the 5-HT-induced contraction of the longitudinal muscles. Neither atropine nor guanethidine affected the contraction. The 5-HT agonists, 5-methylserotonin hydrochloride and mosapride, also evoked concentration-dependent contractions. The 5-HT-induced contraction was enhanced by the 5HT2 receptor antagonist ketanserin and the 5-HT3 receptor antagonist ondansetron but was inhibited by the 5-HT1 receptor antagonist methysergide and 5-HT4 receptor antagonist GR113808. These results indicate that 5-HT1 and 5-HT4 receptors may mediate the contraction of the 5-HT-induced response and 5-HT2 and 5-HT3 receptors may mediate 5-HT-induced relaxation in feline ileal longitudinal smooth muscles.
Atropine ; Benzamides ; Contracts ; Gastrointestinal Tract ; Guanethidine ; Ileum ; Indoles ; Ketanserin ; Methysergide ; Morpholines ; Muscle Contraction ; Muscle, Smooth ; Muscles ; Ondansetron ; Receptors, Serotonin ; Receptors, Serotonin, 5-HT1 ; Receptors, Serotonin, 5-HT3 ; Receptors, Serotonin, 5-HT4 ; Relaxation ; Serotonin ; Serotonin Receptor Agonists ; Sulfonamides ; Tetrodotoxin

In the present study, the antinociceptive profiles of Campanula punctata extract were examined in ICR mice. The Campanula punctata contain a large dose of saponin. Campanula punctata extract administered orally (200 mg/kg) showed an antinociceptive effect as measured by the tail-flick and hot-plate tests. In addition, Campanula punctata extract attenuated the writhing numbers in the acetic acid-induced writhing test. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of substance P (0.7 microgram) was diminished by Campanula punctata extract. Intraperitoneal (i.p.) pretreatment with yohimbine (alpha2-adrenergic receptor antagonist) attenuated antinociceptive effect induced by Campanula punctata extract in the writhing test. However, naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by Campanula punctata extract in the writhing test. Our results suggest that Campanula punctata extract shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of Campanula punctata extract may be mediated by alpha2-adrenergic receptor, but not opioidergic and serotonergic receptors.
Animals ; Campanulaceae ; Methysergide ; Mice ; Mice, Inbred ICR ; Naloxone ; Reaction Time ; Saponins ; Substance P ; Yohimbine

BACKGROUND: Nerve injury may produce a tactile allodynia. However, there are few reports regarding the interaction of morphine and selective serotonin reuptake inhibitors (SSRIs) during a neuropathic pain state. Therefore, we investigated the antiallodynic interaction between morphine and SSRIs in a rat model of neuropathic pain. METHODS: Rats were prepared with a tight ligation of the left fifth and sixth lumbar spinal nerves and chronic intrathecal catheter implantation. Mechanical allodynia was then measured by application of von Frey filaments. Morphine, citalopram and paroxetine were administered intrathecally to obtain the dose-response curves. The 50% effective dose of morphine and citalopram or paroxetine were then coadministered to evaluate the drug interaction. In addition, naloxone and methysergide were administered to examine the reversal of the antiallodynic effect. RESULTS: Intrathecal morphine produced a dose-dependent antagonism of the tactile allodynia, but intrathecal citalopram or paroxetine showed no antiallodynic effects. In addition, a morphine-citalopram or paroxetine combination produced an increase in the withdrawal threshold, but naloxone and methysergide reversed the antiallodynic effect. In addition, no interactions were observed between naloxone and citalopram or paroxetine, or morphine and methysergide. CONCLUSIONS: These results suggest that activation of both micron-opioid and serotonin receptors is required for the increased interaction to occur between morphine and SSRIs administered to reduce tactile allodynia. Thus, serotonin receptors take part in the antiallodynic action of morphine at the spinal level.
Animals ; Catheters ; Citalopram ; Drug Interactions ; Hyperalgesia ; Ligation ; Methysergide ; Morphine ; Naloxone ; Neuralgia ; Paroxetine ; Rats ; Receptors, Serotonin ; Serotonin ; Serotonin Uptake Inhibitors ; Spinal Nerves

Melittin-induced tonic pain model is characterized by local inflammation, edema, spontaneous flinchings, and sustained mechanical hypersensitivity. These nociceptive responses are mediated through selective activation of capsaicin-sensitive primary afferent fibers by melittin. The present study was undertaken to elucidate the role of peripheral 5-hydroxytryptamine (5-HT) receptors in the melittin-induced nociceptive responses. Changes in mechanical threshold, flinching behaviors and paw thickness were measured in rat intraplantarly injected with melittin (40microgram/paw) alone or treated together with melittin and 5-HT receptor antagonists. WAY-100635 (100microgram & 200microgram/paw), isamoltane hemifumarate (100microgram & 200microgram/paw), methysergide maleate (60microgram, 120microgram & 200microgram/paw) and ICS-205,930 (100microgram & 200microgram/paw) were intraplantarly injected 20 min before melittin injection. All 5-HT receptor antagonists tested in this experiment significantly attenuated the ability of melittin to reduce mechanical threshold and to induce flinching behaviors. 5-HT receptor antagonists, except ICS-205,930, had mild inhibitory effect on melittin-induced edema. These experimental findings suggest that multiple peripheral 5-HT receptors are involved in the melittin-induced nociceptive responses.
Animals ; Edema ; Hypersensitivity ; Inflammation ; Melitten ; Methysergide ; Rats* ; Receptors, Serotonin ; Serotonin*

BACKGROUND: Although the efficacy of morphine in a neuropathic pain state is somewhat controversial, spinally administered morphine reversed the tactile allodynia in a previous animal study. Using a behaviorial test, we examined the involvement of serotonergic and adenosine receptors in the mechanism of the antiallodynic action of the intrathecal morphine by injection of serotonergic and adenosine antagonist in a rat model of neuropathic pain induced by a spinal nerve ligation. METHODS: Male Sprague-Dawley rats were prepared with a tight ligation of the left lumbar 5th and 6th spinal nerve and a chronic lumbar intrathecal catheter implantation. Morphine 1 microgram was administered intrathecally to attenuate the tactile allodynia. Methysergide 10 microgram and 30 microgram, theophylline 20 microgram was administered intrathecally before and after the injection of morphine in order to investigate the reversal of an increased allodynic threshold by morphine. The allodynic thresholds for the left hindpaw withdrawl to von Frey hairs were assessed and converted to %MPE. RESULTS: The tactile allodynic threshold was significantly increased by 1 microgram of intrathecal morphine (P < 0.05). Methysergide 10 microgram and 30 microgram, but not theophylline 20 microgram, reversed significantly the antiallodynic effect of intrathecal morphine in pre- and post-treatment (P < 0.05). CONCLUSIONS: The results suggested that the mechanism of tactile antiallodynia induced by intrathecal morphine appears to be mediated by serotonin receptor system at the spinal level in the rat model of spinal nerve ligation.
Adenosine ; Animals ; Catheters ; Hair ; Humans ; Hyperalgesia ; Ligation* ; Male ; Methysergide* ; Models, Animal ; Morphine* ; Neuralgia* ; Rats, Sprague-Dawley ; Receptors, Purinergic P1 ; Serotonin ; Spinal Nerves* ; Theophylline*

Retroperitoneal fibrosis is a slowly progressing syndrome that is a part of a systemic fibrosing disease. Most causes are idiopathic, whereas the remainder are associated with methysergide ingestion, malignancy, or aneurysm of abdominal aorta. The pathogenesis is unclear, but the evidences supporting systemic autoimmune process are present, i.e. the apprearance of autoimmune antibodies, especially antinuclear antibody, positive direct or indirect Coombs' test, and the association with immune thrombocytopenia. Effective treatment with corticosteroid is another suggestion of autoimmune nature of this disease. We experienced a case of retroperitoneal fibrosis with immune thrombocytopenic purpura and positive antinuclear antibody. A 44-years old man who was in splenectomy state due to immune thrombocytopenic purpura for 15 years visited us for obstructive uropathy caused by retroperitoneal fibrosis. He was treated with double J catheter insertion in both ureters, and oral medication of corticosteroid and tamoxifen. Renal failure and thrombocytopenia was improved after treatment and the retroperitoneal fibrotic mass size decreased.
Adult ; Aneurysm ; Antibodies ; Antibodies, Antinuclear ; Aorta, Abdominal ; Autoimmune Diseases ; Catheters ; Coombs Test ; Eating ; Humans ; Methysergide ; Purpura, Thrombocytopenic, Idiopathic* ; Renal Insufficiency ; Retroperitoneal Fibrosis* ; Splenectomy ; Tamoxifen ; Thrombocytopenia ; Ureter

Retroperitoneal fibrosis is a fibroproliferative process involving the retroperitoneum. It may be idiopathic or can be caused by methysergide ingestion, perianeurysmal inflammation, a leaking aneurysm, urinoma or irradiation. The symptoms and signs of retroperitoneal fibrosis are variable, and for diagnosis, imaging is therefore essential. The typical imaging finding is a fibrotic lesion in front of the lower vertebrae with ureteral obstruction. Atypical lesions, however, may occur in other parts of the retroperitoneum. The aim of this report is to describe the clinical features and various imaging findings of etroperitoneal fibrosis.
Aneurysm ; Diagnosis ; Eating ; Fibrosis ; Inflammation ; Methysergide ; Retroperitoneal Fibrosis* ; Spine ; Ureteral Obstruction ; Urinoma