ABSTRACT
Cutaneous electrical or chemical stimulation can produce an anti-inflammatory effect, which is dependent on adrenal medullary-sympathetic activation. We have previously shown that peripheral injection of bee venom (BV) also produces a significant anti-inflammatory effect that is neurally mediated. In the present study, we examined whether this anti-inflammatory effect is also dependent on the adrenal gland using the mouse inflammatory air pouch model. Subcutaneous (s.c.) BV injection produced a marked suppression of leucocyte migration and tumour necrosis factor (TNF)-alpha concentration induced by zymosan injection into the air pouch. The role of the adrenal gland in this suppression was evaluated in adrenalectomized mice. Adrenalectomy significantly reversed the suppression of leucocyte migration and TNF-alpha elevation caused by BV. Serum concentrations of corticosteroid were increased in mice with zymosan-induced air-pouch inflammation and this increase was reduced by BV administration, suggesting that adrenal corticosteroid release is not involved in mediating the anti-inflammatory effects of BV. To test this hypothesis, the corticosteroid receptor antagonist (RU486) was administered and found not to affect the BV-induced inhibition of leucocyte migration. By contrast, pretreatment with the beta-adrenergic antagonist propranolol reversed the BV-induced inhibitory effect on leucocyte migration. These results suggest that the anti-inflammatory effect of s.c. BV administration is mediated in part by the release of catecholamines from the adrenal medulla.
Subject(s)
Adrenal Medulla/immunology , Anti-Inflammatory Agents/pharmacology , Bee Venoms/pharmacology , Inflammation/drug therapy , Adrenal Medulla/metabolism , Adrenalectomy , Adrenergic beta-Antagonists/pharmacology , Animals , Catecholamines/metabolism , Cell Movement/drug effects , Cell Movement/immunology , Disease Models, Animal , Exudates and Transudates/immunology , Hormone Antagonists/pharmacology , Inflammation/chemically induced , Inflammation/immunology , Injections, Subcutaneous , Leukocytes/cytology , Leukocytes/immunology , Male , Mice , Mice, Inbred ICR , Mifepristone/pharmacology , Receptors, Steroid/immunology , Tumor Necrosis Factor-alpha/metabolism , ZymosanABSTRACT
This study is designed to demonstrate the distribution of nociceptin, endogenous ORL1 receptor ligand, in the central nervous system of the Mongolian gerbil. To intensify the nociceptin-like immunoreactivity (NOC-LI), colchicine was administered into the lateral ventricle, at 48 h prior to the transcardiac perfusion. In the group without colchicine treatment, NOC-LI was observed in the fibres of the spinal dorsal horn, specifically in the superficial layers. However, the NOC-LI in the superficial layers disappeared after the administration of colchicine. In the brain, NOC-LI was prominent in the hypothalamus, hippocampus, cerebral peduncle, substantia nigra, dorsal raphe, periaqueductal grey, locus coeruleus and trapezoid nucleus. Colchicine treatment markedly intensified the NOC-LI in the somata of the central nervous system, whereas the untreated sections were too weak to observe and analyse. The distribution of NOC-LI provides informative data for studies of the neuronal circuit that nociceptin may be involved in.
Subject(s)
Central Nervous System/metabolism , Gerbillinae/physiology , Nociceptors/metabolism , Opioid Peptides/metabolism , Animals , Brain/metabolism , Brain/physiology , Colchicine/pharmacology , Gerbillinae/metabolism , Immunohistochemistry/veterinary , Male , Opioid Peptides/immunology , NociceptinABSTRACT
From a clinical perspective, the alternative forms of acupoint stimulation including electroacupuncture, moxibustion and acupressure appear to have more potent analgesic effects than manual needle acupuncture. Bee venom (BV) injection has also been reported to produce persistent nociceptive stimulation and to cause neuronal activation in the spinal cord. In previous study, we observed that BV stimulation into acupoint, namely BV acupuncture or Apipuncture, produced more potent anti-inflammatory and antinociceptive potency in rodent arthritis model as comparing with that of non-acupoint injection. Based on previous report, we decided to further investigate that BV injection into an acupoint produces antinociception as a result of its potent chemical stimulatory effect in both abdominal stretch assay and formalin test. Different doses of BV were injected into an acupoint or a non-acupoint 30 min prior to intraplantar formalin injection or intraperitoneal acetic acid injection. Using the abdominal stretch assay, we found that the high dose of BV (1:100 diluted in 20microl saline) produced a potent antinociceptive effect irrespective of the site of BV injection. In contrast the antinociceptive effect observed in both the writhing and formalin tests following administration of a low dose of BV (1:1000 diluted in 20microl saline) was significantly different between acupoint and non-acupoint sites. BV injection into an acupoint (Zhongwan, Cv. 12) was found to produce significantly greater antinociception than non-acupoint injection (10 mm from Zhongwan, Cv. 12) in the abdominal stretch assay. Similarly, in the formalin test, acupoint (Zusanli, St. 36) injection of BV produced more potent antinociception than non-acupoint injection (gluteal muscle). In contrast, BV injection into an arbitrary non-acupoint site on the back did not produce antinociception in either the writhing or formalin test. These results indicate that BV injection directly into an acupoint can produce a potent antinociceptive effect and suggest that this alternative form of acupoint stimulation (Apipuncture) may be a promising method for the relief of pain.
