Visceral afferent nerve fibers containing substance P or calcitonin gene-related peptide (CGRP) are distributed in the bladder wall, and are known to be stimulated by and then desensitized by capsaicin. Recently, there have been some reports on the effectiveness of intravesical capsaicin administration for the treatment of hypersensitive lower urinary tract disorder or neurogenic bladder. In this study, the effects of intravesical capsaicin on the substance P or CGRP immunoreactivities in the spinal dorsal horn were investigated and the mechanism of capsaicin treatment for bladder disorders was revealed. After intravesical administration of capsaicin, the substance P and CGRP immunoreactive areas were measured at the dorsal horn of L4 and S1 spinal cord. Before capsaicin treatment, the substance P immuno- reactive area was 2.61+/-0.78 x 105 mm2 in L4 and 1.66+/-0.49 x 105 mm2 in S1. The substance P immunoreactivity was markedly reduced 1~2 weeks after capsaicin treatment in both L4 and S1 spinal cord. The CGRP immunoreactive area was 1.74+/-0.52 x 105 mm2 in L4 and 1.14+/-0.69 x 105 mm2 in S1, but was not reduced after capsaicin treatment. Therefore, capsaicin administered intravesically desensitizes nerve fibers containing substance P and consequently suppresses pain and voiding reflex.
Administration, Intravesical ; Animals ; Calcitonin Gene-Related Peptide ; Capsaicin* ; Horns* ; Nerve Fibers ; Rats* ; Reflex ; Spinal Cord ; Substance P ; Urinary Bladder ; Urinary Bladder, Neurogenic ; Urinary Tract ; Visceral Afferents

OBJECTIVETo discuss the effect of calcitonin gene-related peptides (CGRP) on epithelial cadherin (E-cd) expression in human bronchial epithelial cells (HBECs) in vitro.

METHODSThe effect of CGRP on E-cd protein and mRNA expression in both normal and O3-challenged HBECs were determined by immunocytochemistry and RT-PCR. The signal transduction pathways of CGRP were observed by using protein kinase C(PKC) inhibitor (H-7), calmodulin(CaM) inhibitor (W-7) and PKA inhibitor (H-89).

RESULTSCGRP increased E-cd mRNA and protein expressions of normal and O3-challenged HBECs in a dose-dependent manner. CGRP had no effect on cytoplasm E-cd expression. Pre-treatment with H-89, H-7 and W-7, the up-regulatory effect of CGRP on E-cd expression was partly abolished.

CONCLUSIONCGRP increased in cytomembrane E-cd expression of normal and O3-challenged HBECs in a dose-dependent manner. E-cd expression on HBECs was strengthened by CGRP via PKA, PKC and CaM pathways.

Bronchi ; cytology ; Cadherins ; metabolism ; Calcitonin Gene-Related Peptide ; administration & dosage ; pharmacology ; Cell Line ; Epithelial Cells ; drug effects ; metabolism ; Humans ; Ozone ; RNA, Messenger ; genetics

OBJECTIVETo explore the effects of oral administration of mixed enteral nutritional agent on intestinal mucosal barrier of patients with severe burn injury at early stage.

METHODSTwenty-four patients with severe burn injury admitted to our burn ward from August 2013 to September 2014, conforming to the study criteria, were divided into conventional therapy group (n = 12) and early enteral feeding group (n = 12) according to the random number table. Patients in conventional therapy group received conventional treatment immediately after admission, while those in early enteral feeding group were orally given 100 mL of a mixture of glutamine, probiotics, and prebiotics once a day besides conventional treatment for 7 days. Serum levels of diamine oxidase (DAO) and procalcitonin (PCT) and plasma level of LPS were determined by ELISA before treatment and on treatment day (TD) 1, 3, 7, 14, and 21. Wound secretion and blood samples were collected for bacterial culture within the 21 TD. The incidence of MODS within the 21 TD was observed. Data were processed with Fisher's exact test, rank sum test, analysis of variance for repeated measurement, and LSD-t test.

RESULTS(1) Serum levels of DAO in patients of early enteral feeding group on TD 7, 14, and 21 were respectively (14.9 ± 3.7), (12.4 ± 3.1), and (9.5 ± 0.7) ng/mL, which were significantly lower than those of conventional therapy group [(17.5 ± 4.0), (16.3 ± 3.3), and (13.0 ± 1.1) ng/mL, with t values from 2.913 to 15.304, P values below 0.01]. Serum levels of DAO at the other time points were close between the two groups (with t values from -0.598 to 0.139, P values above 0.05). (2) Compared with serum levels of PCT in patients of conventional therapy group [(11.7 ± 20.9) and (12.9 ± 23.9) ng/mL], those of early enteral feeding group were significantly lower on TD 7 and 14 [(2.7 ± 8.1) and (2.0 ± 5.6) ng/mL, with Z values respectively -2.919 and -2.139, P < 0.05 or P < 0.01]. Serum levels of PCT at the other time points were close between the two groups (with Z values from -1.833 to -0.346, P values above 0.05). (3) Plasma level of LPS in patients of early enteral feeding group on TD 7 was (33 ± 56) pg/mL, which was significantly lower than that of conventional therapy group [(102 ± 108) pg/mL, Z = -2.046, P < 0.05]. Plasma levels of LPS at the other time points between the two groups showed no significant difference (with Z values from -2.003~-0.526, P values above 0.05). (4) Positive results in bacterial culture of wound secretion were approximately the same between the two groups (P > 0.05). Bacterial culture of blood was positive in 7 patients of conventional therapy group and 1 patient of early enteral feeding group, showing significantly statistical difference (P < 0.05). MODS was observed in 1 patient of conventional therapy group, showing no significantly statistical difference with that of early enteral feeding group (no patient, P > 0.05).

CONCLUSIONSEarly intestinal feeding of mixed enteral nutritional agent in addition to conventional therapy can effectively promote repair of the impairment of intestinal mucosal barrier, protect integrity of intestinal mucosa, reduce damage to intestines, and alleviate inflammatory response in patients suffering from severe burn injury.

Administration, Oral ; Amine Oxidase (Copper-Containing) ; blood ; Burns ; metabolism ; therapy ; Calcitonin ; blood ; Calcitonin Gene-Related Peptide ; Enteral Nutrition ; methods ; Female ; Glutamine ; administration & dosage ; pharmacology ; Humans ; Intestinal Mucosa ; drug effects ; metabolism ; Protein Precursors ; blood ; Treatment Outcome ; Wound Healing

Spontaneous pain, allodynia and hyperalgesia are well known phenomena following peripheral nerve or tissue injury, and it is speculated that secondary hyperalgesia and allodynia, are generally thought to depend on a hyperexcitability (sensitization) of neurons in the dorsal horn. It is supposed that the sensitization may be due to various actions of neurotransmitters (SP, CGRP, excitatory amino acids) released from the primary afferent fibers. In this study, we examined effects of the iontophoretically applied SP and CGRP on the response to EAA receptor agonists (NMDA and non-NMDA) in the WDR dorsal horn neurones and see if the effects of SP or CGRP mimic the characteristic response pattern known in various pain models. The main results are summarized as follows: 1) SP specifically potentiated NMDA response. 2) CGRP non-specifically potentiated both NMDA and AMPA responses. Potentiation of NMDA response, however, was significantly greater than that of AMPA response. 3) 50% of SP applied cells and 15.8% of CGRP applied cells showed reciprocal changes(potentiation of NMDA response and suppression of AMPA response). These results are generally consistent with the sensitization characteristics in diverse pain models and suggests that the modulatory effects of SP and CGRP on NMDA and non-NMDA (AMPA) response are, at least in part, contribute to the development of sensitization in various pain models.
Animal ; Calcitonin Gene-Related Peptide/pharmacology* ; Calcitonin Gene-Related Peptide/administration & dosage ; Excitatory Amino Acid Agonists/pharmacology* ; Iontophoresis ; Male ; N-Methylaspartate/pharmacology ; Rats ; Rats, Sprague-Dawley ; Spinal Cord/physiology ; Spinal Cord/drug effects* ; Substance P/pharmacology* ; Substance P/administration & dosage ; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/pharmacology

BACKGROUNDProstatodynia remains a difficult clinical problem. Resiniferatoxin (RTX), an ultrapotent vanilloid, can produce a selective and long-lasting desensitization of nociception via C-fiber sensory neurons. Substance P (SP) and calcitonin gene-related peptide (CGRP) released from C-fibers are key neurotransmitters in visceral pain. In this study, we evaluated the analgesic effect of intrathecal RTX on rat prostatodynia.

METHODSMale Sprague-Dawley rats were divided into 3 groups for different treatment. In group A, sham operation was preformed. In group B, 100 microl complete Freund's adjuvant (CFA) was injected into the rat's bilateral ventral prostate to induce chronic inflammation. In group C, after prostatitis formed, 50 microl 10 nmol/L RTX was injected into the rat's lumbosacral (L5-S2) vertebral canal. SP and CGRP contents in the spinal cord were investigated by immunohistochemistry and radioimmunoassay (RIA). Their transcriptional levels in dorsal root ganglion (DRG) were determined by reverse transcriptase polymerase chain reaction (RT-PCR). In addition, pelvic nerve afferent discharge was recorded to explore the neuro-electrophysiological mechanisms underlying RTX-induced effect.

RESULTSSP and CGRP released in the spinal cord and their synthesis in DRG were increased significantly in response to CFA-induced chronic prostatitis, whereas this increase was effectively inhibited by intrathecal RTX. Meanwhile, pelvic nerve afferent electrical activity was enhanced significantly in rats with chronic prostatitis, but it was attenuated markedly in RTX-treated rats paralleled by the change of neuropeptides.

CONCLUSIONSIntrathecal RTX administration could produce an analgesic effect on rat prostatodynia. Suppression of pelvic nerve afferent electrical activity may be a crucial mechanism underlying RTX-induced analgesia. RTX intrathecal application may present a novel analgesic strategy of prostatodynia.

Analgesics ; administration & dosage ; Animals ; Calcitonin Gene-Related Peptide ; analysis ; genetics ; Diterpenes ; administration & dosage ; Injections, Spinal ; Male ; Prostatitis ; drug therapy ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Substance P ; analysis ; genetics

OBJECTIVETo observe effects of point injection at cervical Jiaji points on endothelin (ET) and calcitonin gene related peptide (CGRP) in the patient of ischemic stroke (IS).

METHODSSeventy cases of IS were randomly divided into a treatment group of 35 cases and a control group of 35 cases. The treatment group were treated with acupoint injection at cervical Jiaji points and routine acupuncture, and the control group only with routine acupuncture. Two weeks constituted one course with an interval of one day between courses. After two courses and 4 courses, changes of ET and CGRP were detected, and after 4 courses, their clinical therapeutic effects were evaluated.

RESULTSAcupoint injection at cervical Jiaji points could significantly decrease ET and increase CGRP level; the cured and markedly effective rate was 88.6% in the treatment group and 68.6% in the control group with a significant difference between the two groups (P < 0.05).

CONCLUSIONAcupoint injection at cervical Jiaji points has a very good clinical therapeutic effect and can improve ET and CGRP levels in the patient of IS.

Acupuncture Points ; Adult ; Aged ; Brain Ischemia ; blood ; drug therapy ; Calcitonin Gene-Related Peptide ; blood ; Cervical Vertebrae ; Drugs, Chinese Herbal ; administration & dosage ; Endothelins ; blood ; Female ; Humans ; Injections ; Male ; Middle Aged ; Stroke ; blood ; drug therapy

AIM AND METHODSUsing double immunohistochemical method for Fos and tyrosine hydroxylase(TH) to examine the effects of intracerebroventricular (icv) administration of adrenomedullin (AM) on catecholaminergic neurons and the expression of c-fos gene in rat brain nuclei involved in cardiovascular regulation in order to define whether the effects of central administration of adrenomedullin (AM) were induced by activating the catecholaminergic neurons.

RESULTS(1) Following icy administration of AM (3 nmol/kg), Fos-like immunoreactivity neurons were markedly increased in several brain areas of the rat, including the brainstem, the hypothalamus and the forebrain. (2) Following icy administration of AM (3 nmol/kg), double-labeled neurons for Fos and TH increased significantly in the area postrema (AP), the nucleus of the solitary tract (NTS), the nucleus paragigantocellularis lateralis (PGL) and the locus coeruleus (LC). (3) Pretreatment with calcitonin gene-related peptide receptor antagonism CGRP (8-37) (30 nmol/kg) significantly reduced the action of AM (3 nmol/kg) in the brain.

CONCLUSIONAM activates the nuclei involved in cardiovascular regulation in the forebrain, the hypothalamus and the brainstem, and that the central actions of AM are induced by activating the catecholaminergic neurons of brainstem nuclei involved in cardiovascular regulation. CGRP receptor can mediate the effects of AM in brain.

Adrenomedullin ; administration & dosage ; pharmacology ; Animals ; Brain Stem ; drug effects ; Calcitonin Gene-Related Peptide ; metabolism ; Hypothalamus ; drug effects ; Male ; Neurons ; drug effects ; metabolism ; Peptide Fragments ; metabolism ; Prosencephalon ; drug effects ; metabolism ; Proto-Oncogene Proteins c-fos ; metabolism ; Rats ; Rats, Sprague-Dawley ; Tyrosine 3-Monooxygenase ; metabolism

OBJECTIVE: To observe the effect of ranitidine on gastric acid, plasma endothelin, and calcitonin gene-related peptide (CGRP) in patients undergoing the brain operation, and to explore the possible pathogenesis of ranitidine on preventing from gastric mucosal injury under the stress. METHODS: Thirty patients who underwent brain surgery were randomly divided into 2 groups: Fifteen patients in the control group did not use ranitidine and the other 15 in the treatment group received ranitidine 150 mg intravenously twice daily besides the routine therapy. We continuously monitored the gastric pH value from 4 hours pre-operatively to 72 hours post-operatively in the 30 patients. We also determined the plasma endothelin and CGRP levels of the patients at the 4th hour pre-operatively and at the 4th, 24th, and 72nd hours post-operatively. RESULTS: In the control group there was no significant difference between the mean intra-gastric pH values pre-operatively and post-operatively (P> 0.05). In the treatment group the level of intra-gastric pH was much higher than that in the control group (P< 0.05). In the control group, the level of plasma endothelin significantly higher and the level of calcitonin gene-related peptide significantly lower than that pre-operatively (P< 0.01), but the level of plasma endothelin significantly was lower and the level of calcitonin gene-related peptide obviously higher in the post-operative treatment group than that pre-operatively (P< 0.01). CONCLUSION The brain operation obviously influences the endogenous plasma endothelin and CGRP levels, but its influence on the intra-gastric acid is not visible. Ranitidine can obviously decrease the level of intra-gastric acid, and improve the macrocirculation of gastric mucous membrane by decreasing ET and increasing the CGRP level.
Adult ; Anti-Ulcer Agents ; administration & dosage ; therapeutic use ; Brain ; surgery ; Calcitonin Gene-Related Peptide ; blood ; Endothelin-1 ; blood ; Female ; Gastric Acid ; metabolism ; Humans ; Infusions, Intravenous ; Male ; Middle Aged ; Postoperative Complications ; prevention & control ; Ranitidine ; administration & dosage ; therapeutic use ; Stomach Ulcer ; prevention & control

OBJECTIVE: To investigate the effect of intrathecal sufentanil and protein kinase C inhibitor on pain threshold and the expression of N-methyl-D-aspartate receaptors (NMDAR)/calcitonin generelated peptide (CGRP) in spinal dorsal horn in rats with neuropathic pain. METHODS: Fifty-four healthy male Sprague-Dawley rats were randomly divided into 6 groups (9 in each group). The rats in the sham group(Group S) + spared nerve injury (SNI), SP+SNI, and P+SNI were intrathecally injected sufentanil (1 μg), sufentanil (1 μg) and chelerythrine chloride (11 μg), chelerythrine chloride (11 μg) followed by 10 μL normal saline once every day for 14 days postoperatively, respectively. Similarly, rats in the control group (Group C), the sham group (Group S), and SNI model group (Group SNI) were intrathecally injected 20 μL normal saline in the uniform interval. Pain behaviours were measured on Day 1 pre-surgery and on Day 1, 2, 7, and 14 after the intrathecal injection. The expressions of NMDAR and CGRP in the spinal dorsal horn of L5 segment were determined by immunohistochemistry on Day 2, 7, and 14 after the intrathecal injection. RESULTS: Compared with Group C and Group S, mechanical allodynia threshold in group SNI was decreased after the surgery (P<0.01), and expressions of NMDAR and CGRP immunoreactive soma in the spinal dorsal horn was significantly increased (P<0.01). Mechanical stimulation pain threshold was elevated in Group S+SNI, Group P+SNI, and Group SP+SNI compared with Group SNI (P<0.01), while expressions of NMDAR and CGRP immunoreactive soma in Group S+SNI, Group P +SNI, and Group SP+SNI were significantly decreased (P<0.05 or 0.01). CONCLUSION Intrathecal administration of sulfentanil and protein kinase C inhibitor can provide significant antinociception in rats with neuropathic pain and obviously inhibit the upregulation of NMDAR and CGRP expressions in the spinal dorsal horn of SNI rat models.
Animals ; Benzophenanthridines ; administration & dosage ; Calcitonin Gene-Related Peptide ; metabolism ; Injections, Spinal ; Male ; Neuralgia ; drug therapy ; metabolism ; physiopathology ; Pain Measurement ; Posterior Horn Cells ; metabolism ; Protein Kinase C ; antagonists & inhibitors ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; metabolism ; Sufentanil ; administration & dosage

Reactive oxygen species (ROS) is involved in autoimmune destruction of islet beta cells, which has been proven to be an important underlying pathogenesis for insulin dependent diabetes mellitus (IDDM). Calcitonin gene-related peptide (CGRP) is a widely distributed neuropeptide, which has been found to play an important role in protecting myocytes from ROS. We hypothesized that exogenous CGRP gene administration before the pathogenic stage of insulitis might suppress the production of ROS and provide a hopeful therapeutic intervention for autoimmune diabetes. We performed CGRP gene transfer by injecting naked plasmid directly into skeletal muscles of mice with electroporation enhancement to achieve a continuous expression of CGRP in skeletal muscles, and thereby its secretion into the circulation. The effect of CGRP gene transfer on the pathogenesis of diabetes was studied in autoimmune diabetic mice induced by multiple low dose streptozotocin (MLDS). The CGRP gene therapy decreased morbidity of autoimmune diabetes, and significantly ameliorated hyperglycemia in these mice. CGRP gene transfer inhibited the production of ROS and malondialdehyde (MDA). In addition, it enhanced the activity of catalase (CAT) and superoxide dismutase (SOD) significantly. The data suggest that intramuscular CGRP gene transfer ameliorates autoimmune destruction of islet beta cells, resulting in significant reduction in diabetes incidence of MLDS diabetes mice. CGRP benefits might be mediated at least in part by inhibiting the oxidative stress in islet beta cells of these mice.
Animals ; Calcitonin Gene-Related Peptide ; administration & dosage ; genetics ; therapeutic use ; Diabetes Mellitus, Experimental ; prevention & control ; Diabetes Mellitus, Type 1 ; prevention & control ; Gene Transfer Techniques ; Genetic Therapy ; Injections, Intramuscular ; Islets of Langerhans ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Pancreas ; metabolism ; Reactive Oxygen Species ; metabolism ; Superoxide Dismutase ; metabolism ; Transgenes ; genetics