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PubMed2006

T cell infiltration after chronic constriction injury of mouse sciatic nerve is associated with interleukin-17 expression.

Interleukin (IL)-17A, a recently described novel T cell cytokine, orchestrates inflammation in a variety of immune-mediated diseases. In the present investigation, we analyzed the temporal gene expression pattern of IL-17A and its main regulators IL-23 and IL-15 after chronic constriction injury (CCI) of the sciatic nerve, a lesion paradigm inducing neuropathic pain, by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in mice. IL-17A displayed a monophasic expression in degenerating nerves at day 7 after CCI while transcripts for the IL-17A regulatory cytokines IL-23 and IL-15 peaked earlier. Accordingly, IL-17A positive T cells were detectable within the endoneurium of the injured nerves by immunocytochemistry. In support of a crucial role of T cell inflammation, RAG-1 knockout mice lacking functional T lymphocytes did not express IL-17A mRNA in distal nerve segments following CCI. Interestingly, T cell deficiency was associated with less thermal hyperalgesia and reduced mRNA levels for the macrophage marker molecule F4/80 and the chemokine macrophage chemoattractant protein-1 (MCP-1) after CCI. Our study supports the notion that T cells and T-cell-derived cytokines contribute to the inflammatory response after peripheral nerve injury.

Analysis of Variance↗
PubMed2005

Noninfectious constrictive pericarditis in a heart transplant recipient.

Acute rejection, infection, and allograft coronary artery disease have been recognized as the major causes of postoperative morbidity and mortality in cardiac transplant patients. More recently, pericardial and mediastinal complications have been recognized as a more common complication than previously believed. We describe a case of a heart transplant recipient admitted for apparent congestive heart failure exacerbation who was unresponsive to standard medical management of congestive heart failure and rejection. After further invasive evaluation, it was discovered the patient's condition was attributable to posttransplantation constrictive pericarditis. It is appropriate to consider this diagnosis in any postcardiac surgery (especially heart transplant recipients) in patients presenting with congestive heart failure exacerbations refractory to usual medical management.

Cardiac Catheterization↗
PubMed2006

Constrictive pericarditis: an unusual clinical entity suggested during dobutamine stress echocardiography.

A 44-year-old female presents with disabling dyspnea and is unable to perform a regular treadmill stress test; instead a dobutamine stress echocardiogram is performed and although negative for ischemia reveals a vigorous paradoxical motion of the interventricular septum with dilatation of the inferior vena cava without respiratory variation and an increased diastolic flow signal in the hepatic veins after expiration with the infusion of dobutamine. The diagnosis of constrictive physiology is confirmed with cardiac magnetic resonance imaging (MRI) and right heart hemodynamics and the patient underwent pericardiectomy without complications with resolution of symptoms.

Adult↗
PubMed2005

The efficacy of brain natriuretic peptide levels in differentiating constrictive pericarditis from restrictive cardiomyopathy.

OBJECTIVES: We sought to determine the usefulness of brain natriuretic peptide (BNP) measurements to differentiate constrictive pericarditis (CP) from restrictive cardiomyopathy (RCMP). BACKGROUND: The differentiation of CP from RCMP may be clinically difficult and often requires hemodynamic assessment. No laboratory marker has been shown to differentiate the two conditions. METHODS: We measured BNP levels in 11 patients suspected of having either CP or RCMP. All patients had hemodynamic assessment the day of BNP measurements. RESULTS: Six patients had CP and five patients had RCMP based on established hemodynamic criteria. Both CP and RCMP patients had similar elevation in intracardiac pressures. Despite similar pressures, the mean plasma BNP levels were significantly higher in RCMP compared to CP (825.8 +/- 172.2 pg/ml vs. 128.0 +/- 52.7 pg/ml, p < 0.001, respectively). CONCLUSIONS: The BNP levels are significantly elevated in RCMP compared to CP patients; BNP may prove to be a useful noninvasive marker for the differentiation of the two conditions.

Cardiomyopathy, Restrictive↗
PubMed2006

Selective migration and engraftment of bone marrow mesenchymal stem cells in rat lumbar dorsal root ganglia after sciatic nerve constriction.

Bone marrow mesenchymal stem cells (MSCs) preferentially migrate to the injured hemisphere when administered intravenously to rats with traumatic or ischemic brain injuries. In this study, we have investigated the localization of MSCs injected into the lumbar-4 dorsal root ganglion (L4-DRG) of rats with a sciatic nerve single ligature nerve constriction (SLNC). MSCs were isolated by their adherence to plastic, cultured until confluence and labelled with Hoechst. Animals with a unilateral injection of MSCs were subjected to an ipsilateral, bilateral or contralateral SLNC. After 9 days, they were perfused and the lumbar DRGs were dissected out, cut in a cryostat and observed with a fluorescence microscope. Large numbers of Hoechst-positive cells were observed in the injected L4-DRG, distributed around primary afferent neurons, resembling the anatomical localization of glial cells. In animals with an ipsilateral SLNC, some cells were detected in the ipsilateral L3, L5 or L6-DRGs but not in the contralateral ganglia. In animals with a bilateral lesion, MSCs migrated to both the ipsilateral and contralateral DRGs whereas in animals with a contralateral ligature, MSCs migrated to the contralateral DRGs. These results suggest that MSCs preferentially engraft in DRGs hosting primary sensory neurons affected by a lesion of their peripheral branches. Further studies should be carried out in order to elucidate the molecular mechanisms involved in this migration and homing, in order to evaluate the possible use of MSCs as a new therapeutic strategy for the treatment of peripheral nerve neuropathies.

Animals↗
PubMed2006

Transient loss of terminals from non-peptidergic nociceptive fibers in the substantia gelatinosa of spinal cord following chronic constriction injury of the sciatic nerve.

It is well known that following peripheral nerve injury, there are numerous changes in neurotransmitter and neuropeptide expression in the superficial dorsal horn, the dorsal root ganglion and the periphery. Of particular interest are the relative contributions of two sub-types of unmyelinated C-fibers in the initiation and maintenance of chronic pain, the peptidergic, and the non-peptidergic. Evidence gathered in recent years has led researchers to believe that the non-peptidergic nociceptive primary afferents are functionally distinct from their peptidergic counterpart. For our study, we used a well-established animal model of constriction neuropathy (the Kruger model) and studied Wistar rats at 5, 7, 10, 15 and 21 days after nerve lesion caused by the application of a fixed-diameter polyethylene cuff to the left sciatic nerve. Animals were assessed for the onset and evolution of mechanical allodynia using calibrated von Frey filaments and were additionally tested for thermal (heat and cold) hypersensitivity. Immunocytochemical detection of calcitonin gene-related peptide (CGRP) and isolectin B4 (IB4) binding was used to visualize the dorsal horn distribution of the boutons from the peptidergic and non-peptidergic fibers respectively. Using confocal microscopy and image analysis, we detected a significant decrease in the density of IB4-labeled boutons, ipsilateral to the lesion, at seven and 10 days following nerve injury. The density of IB4-labeled varicosities retuned to control levels by 15 days. There were no significant changes in the density of CGRP-labeled varicosities at all time points examined. Applying electron microscopy, we initially detected degenerative changes in the central elements of type I glomeruli and then a considerable reduction in their number followed by recovery at 15 days post-lesion. As the central boutons of type Ia represent varicosities from the fibers which bind IB4, the ultrastructural changes confirmed that there was a bona fide transient loss of varicosities, not simply a loss of IB4 binding. These data indicate that, in this animal model, morphological changes in the nociceptive C-fiber input of the rat dorsal horn are restricted to the non-peptidergic sub-population and are transient in nature. Furthermore, such changes do not correlate with the time-course of the allodynia.

Animals↗
PubMed2006

Neurotrophin-3 attenuates galanin expression in the chronic constriction injury model of neuropathic pain.

We have recently shown that exogenous neurotrophin-3 (NT-3) acts antagonistically to nerve growth factor (NGF) in regulation of nociceptor phenotype in intact neurons and suppresses thermal hyperalgesia and expression of molecules complicit in this behavioral response induced by chronic constriction injury (CCI) of the sciatic nerve. The present study examines whether there is a global influence of NT-3 in mitigating alterations in peptide and NGF receptor expression; molecules believed to also contribute to CCI-associated pain. Thus, the influence of NT-3 on phenotypic changes in dorsal root ganglion (DRG) neurons in rats coincident with CCI was examined using in situ hybridization. Seven days following injury, the incidence of expression of the neuropeptides galanin and pituitary adenylate cyclase-activating polypeptide (PACAP) was increased in L5 sensory neurons ipsilateral to the injury from 12% to 60% and 16% to 37% respectively, in addition to an increased level of expression. In contrast, there was no consistent significant change in tropomyosin-related kinase A (trkA) expression following CCI. Intrathecal infusion of NT-3 globally mitigated both the increased incidence and elevated levels of galanin messenger RNA (mRNA) expression observed following CCI, reducing the former from 60% to 39%. NT-3 infusion resulted in a limited reduction in the incidence and level of neuronal PACAP in medium to large size, but not small size, DRG neurons. NT-3 had no significant net effect on CCI-induced alterations in trkA mRNA expression.

Animals↗
PubMed2005

Effect of the cannabinoid CB1 receptor antagonist, SR141716, on nociceptive response and nerve demyelination in rodents with chronic constriction injury of the sciatic nerve.

Many reports have shown the efficacy of cannabinoid agonists in chronic pain, whereas no report exists concerning the potential effect of cannabinoid antagonists following prolonged treatment. We tested the effects of repeated administration of the selective cannabinoid receptor type 1 (CB1) antagonist, SR141716 (rimonabant), in rats with chronic constriction injury of the sciatic nerve (CCI), an animal model of neuropathic pain. The repeated oral administration of SR141716 (1, 3 and 10 mg/kg, once a day for 1 week, from day 7 after the injury) dose dependently attenuated both thermal and mechanical hyperalgesia. A similar effect was observed in CCI wild-type mice, whereas SR141716 was unable to elicit pain relief in CB1 knockout mice, suggesting CB1 receptors involvement in the SR141716-induced antihyperalgesia. The antihyperalgesic activity of SR141716 was associated with a significant reduction of several pro-inflammatory and pro-nociceptive mediators such as tumor necrosis factor alpha (TNFalpha), prostaglandin-E2 (PGE2), lipoperoxide and nitric oxide (NO) levels. The histological analysis of sciatic nerve sections showed a marked degeneration of myelinated fibers in CCI rats, which was substantially reduced after repeated administration of SR141716. This suggests that the compound may favour myelin repair and consequently promote long-lasting functional recovery. This was confirmed by the maintenance of recovery for at least four weeks after treatment discontinuation. In conclusion, the present findings suggest that SR141716 is effective not only in alleviating neuropathic pain but also in favouring the nerve myelin repair.

Analysis of Variance↗
PubMed2006

GW406381, a novel COX-2 inhibitor, attenuates spontaneous ectopic discharge in sural nerves of rats following chronic constriction injury.

There are several lines of evidence to suggest that cyclooxygenase-2 (COX-2) plays an important role in the generation and maintenance of neuropathic pain states following peripheral nerve injury. However, COX-2 inhibitors are generally ineffective in reversing mechanical allodynia and hyperalgesia in models of neuropathic hypersensitivity. Here, we have investigated the effects of GW406381, a novel COX-2 inhibitor, on mechanical allodynia, hyperalgesia and generation of spontaneous ectopic discharge in rats following chronic constriction injury (CCI) of the sciatic nerve and compared it with rofecoxib. GW406381 (5mg/kg, 5 days of treatment) significantly reversed the CCI-induced decrease in paw withdrawal thresholds (PWTs), assessed using both von Frey hair and paw pressure tests, whereas an equi-effective dose of rofecoxib (5mg/kg, 5 days of treatment) in inflammatory pain models was ineffective. In rats treated with GW406381, the proportion of fibres showing spontaneous activity was significantly lower (15.58%) than that in the vehicle (32.67%)- and rofecoxib (39.66%)-treated rats. Ibuprofen, a non-selective COX inhibitor, at 5mg/kg, orally dosed three times a day for 5 days did not significantly affect the PWTs in CCI rats. In naïve rats, GW406381 did not significantly change the PWTs. These results illustrate that COX-2 may indeed play an important role in the maintenance of neuropathic pain following nerve injury, but that only certain COX-2 inhibitors, such as GW406381, are effective in this paradigm. Whilst the mechanisms underlying this differential effect of GW406381 are not clear, differences in drug/enzyme kinetic interactions may be a key contributing factor.

Action Potentials↗
PubMed2005

Sildenafil citrate and vacuum constriction device combination enhances sexual satisfaction in erectile dysfunction after radical prostatectomy.

OBJECTIVES: To assess the effectiveness of combining sildenafil citrate with a vacuum constriction device (VCD) in men (after radical prostatectomy) unsatisfied with the results of the VCD alone. METHODS: A total of 31 patients unsatisfied with the early use of VCD alone after radical prostatectomy (mean follow-up of 4.5 months) were instructed to take 100 mg of sildenafil 1 to 2 hours before VCD use for sexual intercourse. Patients used combination therapy for a minimum of five attempts before assessment with the abridged International Index of Erectile Function (IIEF) questionnaire and a visual analogue scale to gauge rigidity. The effect of combination therapy on the total IIEF-5 score and penile rigidity score were assessed. RESULTS: Of the 31 patients, 7 (22%) had no improvement with the addition of sildenafil with VCD and discontinued the drug, and 24 (77%) reported improved penile rigidity and sexual satisfaction. The IIEF-5 score revealed statistically significant improvement in each domain, and patients reported that sildenafil enhanced their erections 100% of the time. The penile rigidity scores on a scale of 0 to 100 with the VCD alone averaged 55% (range 23% to 85%) for the men and 59% (range 26% to 90%) for their partners. With the addition of sildenafil, it increased to 76% for the men and 82% for their partners. Of the 24 men, 7 (30%) reported a return of natural erections at 18 months using combination therapy, with 5 of 7 reporting erections sufficient for vaginal penetration. CONCLUSIONS: In this study, the addition of sildenafil with VCD improved sexual satisfaction and penile rigidity in patients unsatisfied with VCD alone after radical prostatectomy.

Coitus↗
PubMed2001

Pericardiectomy for constrictive pericarditis using the harmonic scalpel.

A 35-year-old man with constrictive pericarditis underwent pericardiectomy. The pericardium was dissected with a Harmonic Scalpel (Ethicon Endo-Surgery, Cincinnati, OH). This new device has many advantages including no muscular stimulation, low heat, a smokeless field, and easy hemostasis. The Harmonic Scalpel is beneficial for dissection of thickened pericardium.

Adult↗
PubMed1976

Constrictive pericarditis.

A patient with constrictive pericarditis following an open-heart operation without sepsis is discussed. In the absence of sepsis, it has been widely held that this complication does not develop following an open-heart procedure. The fatal outcome in this patient could have been avoided had such an association been known.

Aortic Valve↗
PubMed1998

Needle embolus causing cardiac puncture and chronic constrictive pericarditis.

We present a case in which a needle broke off during intravenous injection and embolized to the right heart. After cardiac perforation, the needle entered the pericardial space and ultimately caused chronic constrictive pericarditis, which presented as congestive heart failure. Pericardectomy and removal of the foreign body via a median sternotomy were successful. Early surgical removal of contaminated intrapericardial foreign bodies remains a safe and effective approach to preventing such complications.

Abscess↗
PubMed1998

Fungal purulent constrictive pericarditis in a heart transplant patient.

Purulent pericarditis caused by Candida species is rare and is associated with very high mortality. Immunosuppressed transplant patients are particularly susceptible to fungal infections. We report a case of Candida purulent constrictive pericarditis in an immunocompromised heart transplant patient who was treated successfully with antifungal agents, surgical drainage, and pericardiectomy.

Amphotericin B↗
PubMed1998

High-frequency transcutaneous electrical nerve stimulation alters thermal but not mechanical allodynia following chronic constriction injury of the rat sciatic nerve.

OBJECTIVE: To determine if daily transcutaneous electrical nerve stimulation (TENS) can alter the thermal and mechanical allodynia that develops after chronic constriction injury (CCI) to the right sciatic nerve of rats. DESIGN: A completely randomized experimental design was used. Four groups of rats underwent CCI surgery to the right sciatic nerve and either were not treated with TENS or received TENS starting at different times after the CCI surgery. INTERVENTIONS: TENS was delivered daily for 1 hour to CCI rats through self-adhesive electrodes applied to skin innervated by the right dorsal rami of lumbar spinal nerves L1-6. Rats of different groups received daily TENS starting immediately, 20 to 30 hours, or 3 days after the CCI surgery. MAIN OUTCOME MEASURE: Thermal and mechanical pain thresholds of hind paws were assessed bilaterally in all rats twice before the CCI surgery (baseline) and then 2, 7, 12, and 14 days after surgery. Thermal and mechanical allodynia were expressed as difference scores between the pain thresholds of right and left hind paws. These values were normalized to differences that existed between the two paws at baseline. RESULTS: Daily TENS beginning immediately after CCI surgery prevented the development of thermal allodynia at all assessment times (p < .05). Daily TENS starting 1 day after surgery reduced thermal allodynia, but only on days 2 and 14 (p < .05). Daily TENS beginning 3 days after surgery had no effect on the development of thermal allodynia. Regardless of when it was started, daily TENS did not consistently alter mechanical allodynia in CCI rats. CONCLUSION: It appears that daily TENS can prevent thermal but not mechanical allodynia in this model. However, early intervention with the treatment is critical if it is to be effective at all.

Animals↗
PubMed2003

Effect of intrathecal nocistatin on nociceptin/orphanin FQ analgesia in chronic constriction injury rat.

Nocistatin and nociceptin/orphanin FQ (N/OFQ) are two neuropeptides derived from the same precursor protein, prepronociceptin (ppOFQ), and exhibit different effects on spinal neurotransmission. Nocistatin does not bind to nociceptin/orphanin FQ peptide receptor (NOP), but intrathecal (i.t.) nocistatin has been reported to block the analgesic effect of i.t. N/OFQ. In this study, we investigated the effect of i.t. nocistatin on N/OFQ analgesia to radiant thermal stimuli in chronic constriction injury (CCI) rat. Firstly, to investigate the analgesic effect of N/OFQ, different doses of N/OFQ (3, 10, 30 microg) were intrathecally injected and foot withdrawal latency (FWL) to radiant heat was recorded. It is observed that 3 microg N/OFQ had no effect on FWL, 10 and 30 microg N/OFQ significantly increased FWL of CCI rat. Then, 10 microg N/OFQ, 10 microg nocistatin and a drug cocktail including 10 microg N/OFQ and 10 microg nocistatin were intrathecally injected. The results showed that FWL significantly decreased after using N/OFQ and nocistatin compared with using only N/OFQ, and 10 microg nocistatin had no effect on FWL versus control, suggesting that this dose of nocistatin per se had no effect on the pain threshold of CCI rat, but could block the analgesic effect of N/OFQ. These results indicated that i.t. N/OFQ dose-relatedly depressed thermal hyperalgesia produced by CCI and nocistatin could block N/OFQ analgesia at spinal level in CCI rat.

Analgesics, Opioid↗
PubMed1999

Myelinated afferents sprout into lamina II of L3-5 dorsal horn following chronic constriction nerve injury in rats.

In order to investigate the consequences of chronic constriction injury (CCI) to nerve, we explored the relationship between the development of mechanical allodynia and the reorganization of primary afferent terminals in the sensory lamina of the rat spinal cord dorsal horn. Following sciatic CCI neuropathy, mechanical allodynia developed in the corresponding footpad within two weeks and persisted throughout the experimental period which extended for an additional two weeks. The neuropathy of the sciatic injury includes extensive Wallerian-like degeneration of myelinated fibers but relative sparing of unmyelinated fibers. We observed that there was no significant change in the dorsal horn termination of unmyelinated C fibers in lamina II of the dorsal horn, using nerve injections of wheat germ agglutin-horseradish peroxidase for transganglionic axonal tracing of these fibers from the nerve injury site, and no evidence of sprouting into adjacent lamina. In contrast, myelinated afferent fibers were observed to be sprouting into lamina II of the dorsal horn, as indicated by cholera toxin beta-subunit-horseradish peroxidase retrograde axonal tracings. This region of the dorsal horn is associated with nociceptive-specific neurons that are not generally associated with myelinated fiber input from mechanical and proprioceptive receptors. As previously suggested in nerve transection and crush injuries, and now demonstrated in CCI neuropathy, these morphological changes may have significance in the pathogenesis of chronic mechanical allodynia.

Afferent Pathways↗
PubMed2003

Delayed presentation of paediatric penile constrictive band injury.

We report the case of a child with delayed presentation of partial amputation of the penis with complete transaction of the urethra following a self-inflicted constrictive band injury. Single-stage reconstruction of the urethra and corporae achieved a satisfactory immediate outcome.

Child↗