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PubMed2004

Ligneous (pseudomembranous) inflammation involving the female genital tract associated with type-1 plasminogen deficiency.

Ligneous (pseudomembranous) inflammation of the female genital tract is a rare and unusual condition characterized by extensive subepithelial fibrin deposition and associated inflammation. Ligneous inflammation in extragenital sites, predominantly the conjunctiva, has been linked to plasminogen deficiency. Individuals with plasminogen deficiency are unable to remove fibrin deposited in injured mucosal tissue. Severe systemic ligneous inflammation involving the female genital tract that is linked to hypoplasminogenemia has not previously been described. We present a patient with ligneous inflammation of her genital, middle ear, and oral mucosa that was associated with type-1 homozygous plasminogen deficiency due to a novel missense mutation in the plasminogen gene.

DNA↗
PubMed2004

Occult pretransplantation systemic inflammation and posttransplantation vascular changes in a primate arterial allograft model.

BACKGROUND: Occult systemic inflammation, as manifested by increased levels of C-reactive protein (CRP), identify patients at increased risk for renal allograft rejection. The mechanisms linking occult systemic inflammation to these adverse outcomes remain unclear. The purpose of this study was to examine the anatomic and physiologic effects of occult pretransplantation systemic inflammation on posttransplantation allograft outcome in a nonhuman primate model. METHODS: Seventy-one healthy male Rhesus macaques were stratified into quartiles based on serum CRP. Five high quartile and six low quartile animals underwent common iliac artery transplantation from male donors. Duplex ultrasound measured graft flow at 3 weeks postoperatively; luminal narrowing was assessed by graft/femoral peak systolic velocity ratio. At 6 weeks, the grafts were harvested and morphometry studies were performed. Vessel wall changes were assessed by measuring the intimal medial area. RESULTS: The allografts placed in high CRP quartile animals had more luminal narrowing by 3 weeks than those placed in low quartile animals, as evidenced by a higher mean graft/femoral peak systolic velocity ratio (1.6 vs. 0.90, P=0.006). Morphometry studies after graft harvest showed increased vessel wall area in the high quartile group versus the low quartile group (1.39 mm vs. 1.03 mm, P=0.018). CONCLUSIONS: Occult pretransplantation systemic inflammation is associated with increased intimal thickening and stenosis after arterial allograft transplantation in a primate model. Additional studies are needed to confirm these results and to further investigate potential mechanisms linking pretransplantation systemic inflammation to adverse outcomes after transplantation.

Animals↗
PubMed2014

Persistent inflammation, immunosuppression, and catabolism syndrome after severe blunt trauma.

BACKGROUND: We recently proffered that a new syndrome persistent inflammation, immunosuppression, and catabolism syndrome (PICS) has replaced late multiple-organ failure as a predominant phenotype of chronic critical illness. Our goal was to validate this by determining whether severely injured trauma patients with complicated outcomes have evidence of PICS at the genomic level. METHODS: We performed a secondary analysis of the Inflammation and Host Response to Injury database of adults with severe blunt trauma. Patients were classified into complicated, intermediate, and uncomplicated clinical trajectories. Existing genomic microarray data were compared between cohorts using Ingenuity Pathways Analysis. Epidemiologic data and outcomes were also analyzed between cohorts on admission, Day 7, and Day 14. RESULTS: Complicated patients were older, were sicker, and required increased ventilator days compared with the intermediate/uncomplicated patients. They also had persistent leukocytosis as well as low lymphocyte and albumin levels compared with uncomplicated patients. Total white blood cell leukocyte analysis in complicated patients showed that overall genome-wide expression patterns and those patterns on Days 7 and 14 were more aberrant from control subjects than were patterns from uncomplicated patients. Complicated patients also had significant down-regulation of adaptive immunity and up-regulation of inflammatory genes on Days 7 and 14 (vs. magnitude in fold change compared with control and in magnitude compared with uncomplicated patients). On Day 7, complicated patients had significant changes in functional pathways involved in the suppression of myeloid cell differentiation, increased inflammation, decreased chemotaxis, and defective innate immunity compared with uncomplicated patients and controls. Subset analysis of monocyte, neutrophil, and T-cells supported these findings. CONCLUSION: Genomic analysis of patients with complicated clinical outcomes exhibit persistent genomic expression changes consistent with defects in the adaptive immune response and increased inflammation. Clinical data showed persistent inflammation, immunosuppression, and protein depletion. Overall, the data support the hypothesis that patients with complicated clinical outcomes are exhibiting PICS. LEVEL OF EVIDENCE: Epidemiologic study, level III.

Adolescent↗
PubMed2006

Inflammation of the gonad in prepubertal healthy children. Epidemiology, etiology, and management.

The prevalence, etiology, and proper management of acute gonadal inflammation in prepubertal children are still controversial, with some reports defining it as rare, while others have found it more prevalent. So far, there is no consensus on imaging studies or standard follow-up procedures. In the minority of the children, the inflammation is related to congenital genitourinary malformation and bacterial infection. The majority of children with gonadal inflammation are healthy and do not have any underlying malformations; in this group, the etiology is related to viral infection or torsion of the gonad appendix. Management is directed towards the etiology. Hence, when bacterial inflammation is suspected, antibiotics should be given and full evaluation of the urinary tract system should be performed. For patients with negative medical history, absence of fever, and normal urinalysis, the diagnosis of bacterial inflammation is very unlikely, and there is neither justification for antimicrobial antibiotic therapy nor for any further urinary tract imaging. Caution should be taken with nonverbal children and infants, or patients with any abnormal parameter. For these patients, we recommend initial management as for bacterial urinary tract infection, until urine cultures results are obtained. This paper provides a comprehensive review with the related medical literature.

Child↗
PubMed1984

Intradermal injection of Propionibacterium acnes: a model of inflammation relevant to acne.

The intradermal injection of 140 micrograms of Propionibacterium acnes (CN 6134) into the ears of female Sprague-Dawley rats produced a chronic inflammation with formation of acneiform lesions. Inflammation was characterized by more than a doubling of ear thickness at 24 h and a peak of 3-4 times control levels at day 21. At 42 days post injection ears were still 3 times normal thickness. Histologically there was early polymorph accumulation giving way to macrophages and lymphocytes by day 7. Pilosebaceous follicles overlying the inflamed area lost their sebaceous glands and became hyperplastic cords of cells that grew down and encapsulated inflammatory loci. By day 9 many of these follicles had become secondary comedones. Three isolates of P. acnes from inflammatory acne lesions and 4 of 5 isolates from non-acne patients produced results similar to that of the strain CN 6134. In these cases the number of histologically evident secondary comedones was correlated with ear thickness. In contrast, samples of Streptococcus lactis, Escherichia coli B, and Staphylococcus epidermidis failed to produce this combination of chronic inflammation and high lesion count. Benzoyl peroxide, tetracycline, erythromycin, phenidone, naproxen, and cis and trans retinoic acid were inactive as inhibitors of P. acnes CN 6134-induced ear thickening. The corticosteroid fluocinolone acetonide produced dramatic suppression of inflammation, but upon cessation of treatment the ears returned to inflamed levels. The specificity for P. acnes, the formation of acneiform lesions, and the recalcitrance of the inflammation suggest our model is indeed relevant to acne.

Acne Vulgaris↗
PubMed2002

Role of inflammation in cardiovascular disease: how to use C-reactive protein in clinical practice.

Acute coronary syndromes, stroke, and sudden death are common complications of a disrupted atherosclerotic plaque. Unstable plaque is a result of multiple factors but is commonly characterized by an infiltrate of inflammatory cells. Medical research strongly supports a role for inflammation in the pathogenesis, progression, and disruption of atherosclerotic plaque. Medical science also has improved our understanding of the complex interactions between our environment and our immune, coagulation, and cardiovascular systems. Clinical studies have demonstrated systemic markers of inflammation to be strong predictors of clinical events, and specific treatments of atherosclerosis and its risk factors have been associated with reductions in inflammatory markers. The authors review the current understanding of the role of inflammation in the pathogenesis of atherosclerosis, the common inflammatory markers, and potential anti-inflammatory therapy. Among several potential circulating markers of vascular inflammation, high sensitivity C-reactive protein is best validated and standardized as a marker for cardiovascular risk assessment. Nevertheless, there remain many uncertainties in utilizing C-reactive protein in clinical practice. Here, the authors describe the central role of C-reactive protein in atherosclerosis, review the studies demonstrating predictive value of C-reactive protein, describe the factors requiring consideration when utilizing C-reactive protein, discuss clinical scenarios in which measurement of C-reactive protein may be helpful, and suggest ways to interpret and treat elevated C-reactive protein levels. Finally, the authors summarize future expectations for assessing and modulating the vascular inflammation to inhibit initiation and progression of the atherosclerotic process.

Age Factors↗
PubMedDate not supplied

Serum albumin: relationship to inflammation and nutrition.

Hypoalbuminemia is the result of the combined effects of inflammation and inadequate protein and caloric intake in patients with chronic disease such as chronic renal failure. Inflammation and malnutrition both reduce albumin concentration by decreasing its rate of synthesis, while inflammation alone is associated with a greater fractional catabolic rate (FCR) and, when extreme, increased transfer of albumin out of the vascular compartment. A vicious cascade of events ensues in which inflammation induces anorexia and reduces the effective use of dietary protein and energy intake and augments catabolism of the key somatic protein, albumin. Hypoalbuminemia is a powerful predictor of mortality in patients with chronic renal failure, and the major cause of death in this population is due to cardiovascular events. Inflammation is associated with vascular disease and likely causes injury to the vascular endothelium, and hypoalbuminemia as two separate expressions of the inflammatory process. Albumin has a myriad of important physiologic effects that are essential for normal health. However, simply administering albumin to critically ill patients with hypoalbuminemia has not been shown to improve survival or reduce morbidity. Thus the inference from these clinical studies suggests that the cause of hypoalbuminemia, rather than low albumin levels specifically, is responsible for morbidity and mortality.

Animals↗
PubMed2005

Macrophage activation switching: an asset for the resolution of inflammation.

Macrophages play a central role in inflammation and host defence against microorganisms, but they also participate actively in the resolution of inflammation after alternative activation. However, it is not known whether the resolution of inflammation requires alternative activation of new resting monocytes/macrophages or if proinflammatory activated macrophages have the capacity to switch their activation towards anti-inflammation. In order to answer this question, we first characterized differential human macrophage activation phenotypes. We found that CD163 and CD206 exhibited mutually exclusive induction patterns after stimulation by a panel of anti-inflammatory molecules, whereas CCL18 showed a third, overlapping, pattern. Hence, alternative activation is not a single process, but provides a variety of different cell populations. The capacity of macrophages to switch from one activation state to another was then assessed by determining the reversibility of CD163 and CD206 expression and of CCL18 and CCL3 production. We found that every activation state was rapidly and fully reversible, suggesting that a given cell may participate sequentially in both the induction and the resolution of inflammation. These findings may provide new insight into the inflammatory process as well as new fields of investigation for immunotherapy in the fields of chronic inflammatory diseases and cancer.

Anti-Inflammatory Agents↗
PubMed2006

Role of TNF-alpha in muscularis inflammation and motility disorder in a TNBS-induced colitis model: clues from TNF-alpha-deficient mice.

Macroscopic and histological analysis revealed that the colonic inflammation induced by 2,4,6-trinitrobenzenesulphonic acid (TNBS) was of lower grade in tumour necrosis factor-alpha (TNF-alpha)(-/-) mice than in wild-type mice. Myeloperoxidase activity, an indicator of neutrophilic infiltration, was also low in both the mucosal and smooth muscle layer of the TNF-alpha(-/-) mouse colon. After the induction of inflammation with TNBS, the levels of proinflammatory cytokines, such as TNF-alpha, interleukin-1beta and interleukin-6, were elevated both in the inflamed mucosa and muscle layers in the wild-type mice; however, the productions of these cytokines were greatly reduced in the TNF-alpha(-/-) mouse colon. The contractions of isolated colonic smooth muscle strips induced by several stimulatory agents were significantly decreased after treatment with TNBS in wild-type mice; however, these contractions were scarcely affected in TNF-alpha(-/-) mice. Finally, using the organ culture method, we found that TNF-alpha directly (independent of mucosal inflammation) disturbs the smooth muscle function. These results suggest that TNF-alpha plays an essential role not only in mucosal inflammation but also in muscularis inflammation in the colon of mice with TNBS-induced colitis, and that TNF-alpha directly induces motor dysfunctions by acting on the smooth muscle.

Animals↗
PubMed2006

Changes in airway inflammation following nasal allergic challenge in patients with seasonal rhinitis.

BACKGROUND: Seasonal allergic rhinitis could predispose to the development of chronic bronchial inflammation as observed in asthma. However, direct links between nasal inflammation, bronchial inflammation and airway responsiveness in patients with seasonal allergic rhinitis and without asthma are not fully understood. The aim of this study was to analyse the changes induced by allergic nasal challenge outside the pollen season in airway responsiveness and bronchial inflammation of patients with seasonal allergic rhinitis. METHODS: Nine patients were evaluated after either grass pollens or placebo nasal challenge in a randomized cross-over double-blinded trial. Nasal parameters were recorded hourly and airway responsiveness was assessed by methacholine challenge. Cytological examinations and cytokine measurements were performed in nasal lavage and induced sputum. Eosinophil activation was investigated by eosinophil-cationic protein expression and secretion. RESULTS: Airway responsiveness was increased after allergic nasal challenge. Total eosinophils and eosinophils expressing eosinophil-cationic protein were increased in induced sputum after allergic nasal challenge. Both eosinophil number and eosinophil-cationic protein concentration in induced sputum were correlated to methacholine responsiveness. CONCLUSIONS: These results suggest that eosinophils participate to the bronchial inflammation in patients with seasonal allergic rhinitis following allergic nasal challenge outside the pollen season and might explain changes in airway responsiveness.

Adult↗
PubMed1995

Expression of vascular permeability factor (VPF/VEGF) messenger RNA by plasma cells: possible involvement in the development of edema in chronic inflammation.

Edema occurs in some types of chronic inflammation such as nasal polyps, uterine cervical polyps and gastric hyperplastic polyps. However, the factors or cellular components involved in the development of edema in chronic inflammation remain to be clarified. Recently, the gene encoding vascular permeability factor (VPF) or vascular endothelial growth factor (VEGF) and the genes encoding its receptors (kinase insert domain-containing receptor (KDR) and fms-like tyrosine kinase-1 [fit-1]) have been cloned. VPF/VEGF induces vascular hyperpermeability and vascular endothelial proliferation through KDR or fit-1 receptors. As there is a possibility that VPF/VEGF may play a role in the development of edema in chronic inflammation, we examined the messenger (m) RNA expression of VPF/VEGF and its receptors in nasal polyp tissues, which is an example of chronic inflammation with remarkable edema. Using northern blotting, all nasal polyp tissues examined expressed mRNA of VPF/VEGF and KDR. In situ hybridization revealed that VPF/VEGF mRNA-expressing cells were scattered in the edematous stroma of nasal polyps. In the adjacent sections, these cells showed the morphological features of plasma cells and expressed mRNA of immunoglobulin light chains. Human B cell leukemia and plasmacytoma cell lines expressed VPF/VEGF mRNA but human mast-cell leukemia and T cell leukemia cell lines did not. The alternatively spliced pattern of VPF/VEGF transcripts observed in nasal polyp tissues was consistent with that in plasmacytoma cell lines. Taken together, the VPF/VEGF mRNA-expressing cells in nasal polyps appeared to be plasma cells, suggesting that plasma cells may play an important role in the development of edema in chronic inflammation through the production of VPF/VEGF.

Base Sequence↗
PubMed2004

C-reactive protein, its role in inflammation, Type 2 diabetes and cardiovascular disease, and the effects of insulin-sensitizing treatment with thiazolidinediones.

Increased concentrations of the marker of inflammation, C-reactive protein (CRP), are associated with insulin resistance, Type 2 diabetes and the development of cardiovascular disease. In particular, inflammation is closely associated with endothelial dysfunction and is recognized as one of the cardiovascular risk factors clustering in the Insulin Resistance Syndrome or Metabolic Syndrome. The exact mechanisms linking insulin resistance and inflammation remain unclear. However, the close association between insulin resistance and inflammation in atherogenesis suggests that therapies that address both parameters may have benefits in reducing diabetes-related macrovascular complications. The thiazolidinedione class of oral anti-diabetic agents are powerful insulin sensitizers that also have anti-inflammatory properties. Treatment with these agents has a range of anti-atherogenic effects, including reduced levels of CRP, plasminogen activator inhibitor-1 (PAI-1), TNF-alpha and reactive oxygen species. Additionally, the insulin-sensitizing effect of thiazolidinediones improves other factors of the Insulin Resistance Syndrome, including dyslipidaemia and hypertension. Outcome studies are underway to determine if the effects of improving insulin sensitivity and reducing inflammation will translate into clinical benefits and reduce the cardiovascular morbidity and mortality associated with insulin resistance and Type 2 diabetes.

Arteriosclerosis↗
PubMed2005

Increased plasma markers of inflammation and endothelial dysfunction and their association with microvascular complications in Type 1 diabetic patients without clinically manifest macroangiopathy.

AIMS: To evaluate whether plasma biomarkers of inflammation and endothelial dysfunction differed in Type 1 diabetic patients as compared with those in non-diabetic subjects, and to examine the association of these biomarkers with early stages of microvascular complications. METHODS: Plasma biomarkers of inflammation [fibrinogen, hs-C-reactive protein (hs-CRP)] and endothelial dysfunction [von Willebrand factor (v-WF), intercellular adhesion molecule-1, plasminogen activator inhibitor-1 (PAI-1) activity] were measured in 88 non-smoking young patients with Type 1 diabetes without clinical macrovascular disease and in 40 healthy controls. RESULTS: Plasma levels of hs-CRP, fibrinogen, v-WF, soluble intracellular adhesion molecule-1 (sICAM-1) and PAI-1 activity were markedly higher (P < 0.01 or less) in Type 1 diabetic patients than in healthy controls; these results were essentially unchanged when healthy controls were compared with patients without complications. After stratification by microvascular complication status, plasma biomarkers of inflammation and endothelial dysfunction were significantly increased in those with more advanced disease compared with those with early complications or without complications, respectively. However, while the significant differences in these biomarkers were little affected by adjustment for sex, age, BMI and blood pressure values, they were totally abolished after additional adjustment for diabetes duration and glycaemic control. CONCLUSIONS: These results indicate that in Type 1 diabetes there is a subclinical, chronic inflammation which is, at least partly, independent of clinically manifest macro- and microvascular complications, smoking or other traditional cardiovascular risk factors; this subclinical inflammation is closely correlated to the magnitude and duration of hyperglycaemia.

Adult↗
PubMed1989

Pharmacological modulation of neurogenic inflammation.

A neurogenic inflammation was induced by electrical stimulation of the exposed saphenous or sciatic nerve of male rats. The increase in paw weight of the stimulated leg was used as parameter for degree of inflammation. The content of substance P decreased significantly in the skin supplied by the antidromic stimulated nerves. Substances were tested whose effectivity in neurogenic inflammation is as yet unknown. Inhibition of the angiotensin converting enzyme by the inhibitor captopril did not yield an indirect reference for a causative role of substance P in neurogenic inflammation. The activity of catecholamines refers to the possible importance of blood vessel and/or cyclic nucleotide level alteration in this special type of inflammation.

Animals↗
PubMed1986

Binding to serum alpha 1-acid glycoprotein and effect of beta-adrenoceptor antagonists in rats with inflammation.

The beta-blocking effect of 4 beta-adrenoceptor antagonists with different pharmacokinetic properties was studied after intravenous and intraportal administration to control rats and to rats with experimental inflammation. In rats with inflammation the effects of propranolol and oxprenolol, which are mainly bound to alpha 1-acid glycoprotein (alpha 1-AGP), were significantly less after intravenous administration, but not after intraportal administration. In contrast, for metoprolol and atenolol, which are only negligibly serum bound, no difference was observed between control rats and rats with inflammation for either route of administration. Total and unbound serum concentrations of propranolol were measured 20 min after intravenous and intraportal administration. After intravenous administration, in the rats with inflammation total concentrations of propranolol were more than twice, and unbound concentrations less than half those of control rats. After intraportal administration the total concentrations were 8 times, and the unbound concentrations 3 times higher in the rats with inflammation. There was a significant correlation between the beta-blocking effect and the unbound concentrations of propranolol after intravenous administration, but not after intraportal administration. The latter finding is probably because the unbound concentrations were supramaximal.

Adrenergic beta-Antagonists↗
PubMed1993

Cholecystokinin as a factor in the enhanced potency of spinal morphine following carrageenin inflammation.

1. Cholecystokinin (CCK) has been shown to diminish opioid analgesia. Here we investigate whether changes in the physiological levels of spinal CCK are responsible for the enhanced potency of spinal morphine in animals following carrageenin inflammation, as compared with normal animals. 2. Single dorsal horn nociceptive neurones were recorded in intact halothane-anaesthetized rats in the presence and absence of carrageenin-induced inflammation and comparisons were made between the two groups of animals. Inflammation was induced by the injection of 100 microliters of 2% lambda-carrageenin into the hind paw. 3. The inhibitory effect of intrathecal morphine on the C-fibre-evoked responses of the neurones was enhanced in the carrageenin-treated animals such that the effects of 0.25 microgram and 10 micrograms of morphine in normal animals were comparable to those of 0.01 microgram and 2.5 micrograms in the carrageenin animals. The effect of 0.2 mg kg-1 of the CCKB antagonist, L-365,260, on the antinociceptive potency of intrathecal morphine was examined in both groups of animals. In normal animals, L-365,260 produced a significant enhancement in the effect of morphine indicating a tonic CCK modulation in these animals, but it had no effect on the inhibitions produced by either dose of morphine in the carrageenin animals. 4. The inhibition of the C-fibre-evoked response produced by intrathecal morphine in the presence of 1 microgram of CCK was examined in both groups of animals. CCK attenuated the effects of morphine only in animals with carrageenin inflammation, having no effect on the action of morphine in normal animals. 5. The effects of both CCK and L-365,260 were therefore dependent on the inflammatory state of the animal, with each drug being active in opposite situations.6. We propose that in normal animals, morphine may produce a maximal stimulation of the release of CCK such that exogenous CCK is unable to reduce further the analgesic effects under these conditions.However, the differential effects of the agonist and antagonist in the normal and inflamed rats points to a role of CCK in the enhanced opiate actions. This enhancement of the potency of spinal morphine in inflammation is best explained by a reduction in spinal CCK release by morphine in this state.

Animals↗
PubMed1995

Contribution of interleukin-1 beta to the inflammation-induced increase in nerve growth factor levels and inflammatory hyperalgesia.

1. Peripheral inflammation is associated with the local production of neuroactive inflammatory cytokines and growth factors. These may contribute to inflammatory pain and hyperalgesia by directly or indirectly altering the function or chemical phenotype of responsive primary sensory neurones. 2. To investigate this, inflammation was produced by the intraplantar injection of complete Freund's adjuvant (CFA) in adult rats. This resulted in a significant elevation in interleukin-1 beta (IL-1 beta) and nerve growth factor (NGF) levels in the inflamed tissue and of the peptides, substance P and calcitonin gene-related peptide (CGRP) in the L4 dorsal root ganglion 48 h post CFA injection. 3. The effects of a steroidal (dexamethasone) and a non-steroidal (indomethacin) anti-inflammatory drug on the levels of NGF and IL-1 beta in inflamed tissue were investigated and compared with alterations in behavioural hyperalgesia and neuropeptide expression in sensory neurones. 4. Systemic dexamethasone (120 micrograms kg-1 per day starting the day before the CFA injection) had no effect on the inflammatory hyperalgesia. When the dose was administered 3 times daily, a reduction in mechanical and to a lesser extent thermal sensitivity occurred. Indomethacin at 2 mg kg-1 daily (i.p.) had no effect on the hyperalgesia and a dose of 4 mg kg-1 daily was required to reduce significantly mechanical and thermal hypersensitivity. 5. The increase in NGF produced by the CFA inflammation was prevented by both dexamethasone and indomethacin, but only at the higher dose levels. Dexamethasone at the lower and higher dose regimes diminished the upregulation of IL-1 beta whereas indomethacin had an effect only at the higher dose. 6. The increase in SP and CGRP levels produced by the CFA inflammation was prevented by dexamethasone and indomethacin at the lower and higher dose regimes. 7. Intraplantar injections of IL-1 beta (0.01, 0.1 and 1 ng) produced a brief (6 h) thermal hyperalgesia and an elevation in cutaneous NGF levels which was prevented by pretreatment with human recombinant IL-1 receptor antagonist (IL-1 ra) (0.625 microgram, i.v.). The thermal hyperalgesia but not the NGF elevation produced by intraplantar IL-1 beta (1 ng) was prevented by administration of a polyclonal neutralizing anti-NGF serum. 8. IL-1 ra significantly reduced the mechanical hyperalgesia produced by CFA for 6 h after administration as well as the CFA-induced elevation in NGF levels. Anti-NGF pretreatment substantially reduced CFA-induced mechanical and thermal hyperalgesia without reducing the elevation in IL-1 beta. 9. Intraplantar NGF (0.02, 0.2 and 2 microg) injections produced a short lasting thermal and mechanical hyperalgesia but did not change IL-1beta levels in the hindpaw skin.10. Our results demonstrate that IL-1beta contributes to the upregulation of NGF during inflammation and that NGF has a major role in the production of inflammatory pain hypersensitivity.

Animals↗
PubMed1996

Intrathecal CGRP8-37-induced bilateral increase in hindpaw withdrawal latency in rats with unilateral inflammation.

1. Recent work in our laboratory has demonstrated that intrathecal administration of a selective antagonist of calcitonin gene-related peptide (CGRP), CGRP8-37, increased the hindpaw withdrawal latency (HWL) to thermal stimulation and hindpaw withdrawal threshold (HWT) to pressure in normal rats, and that these effects were more pronounced than in rats with mononeuropathy. 2. The present study was performed to investigate the effects of intrathecal administration of CGRP8-37 on the HWL and HWT in rats with unilateral hindpaw inflammation induced by subcutaneous injection of carrageenin. The effect of naloxone was also studied. 3. Subcutaneous injection of 0.1 ml of carrageenin into the plantar region of the left hindpaw induced a significant increase in the volume of the ipsilateral hindpaw (P < 0.001), and significant bilateral decreases of the HWL to thermal stimulation (ipsilateral: P < 0.001; contralateral: P < 0.01) and HWT to pressure (ipsilateral: P < 0.001; contralateral: P < 0.01). 4. Intrathecal administration of 10 nmol of CGRP8-37, but not of 1 or 5 nmol, induced a significant bilateral increase in the HWL and HWT in rats with experimentally induced inflammation (thermal test: P < 0.001; mechanical test: P < 0.001). 5. The effect of intrathecal administration of 10 nmol CGRP8-37 on HWL and HWT was significantly more pronounced in intact rats than in rats with experimentally induced inflammation (ipsilateral: P < 0.001; contralateral: P < 0.001). 6. The effect of CGRP8-37 on withdrawal responses in the inflamed paw was partly reversed by intrathecal injection of naloxone at a dose of 88 nmol in the thermal (ipsilateral: P < 0.01; contralateral: P = 0.14) and mechanical tests (ipsilateral: P < 0.05; contralateral: P = 0.60). 7. A significant bilateral increase in the concentration of CGRP-like immunoreactivity in the perfusate of both hindpaws was demonstrated 24 h after unilateral injection of carrageenin (ipsilateral: P < 0.001; contralateral: P < 0.05). There was also an increase in the amount of CGRP-like immunoreactivity in the cerebrospinal fluid (P < 0.001), but not in plasma (P = 0.75). 8. The present study demonstrates that acute experimentally-induced unilateral hindpaw inflammation, induces bilateral increases in the amount of CGRP-like immunoreactivity in hindpaw perfusates. Intrathecal administration of CGRP8-37 increased the HWL to thermal stimulation and HWT to pressure bilaterally. 9. The results indicate that CGRP plays a role in the transmission of presumed nociceptive information in the spinal cord of rats with experimentally induced inflammation. Furthermore, our findings suggest that opioids can modulate CGRP-related effects in the spinal cord.

Animals↗