Biomedical subjects

David Martin

Publications and source records attributed to David Martin.

At least 55 records · Page 3Linked to original sources

PubMed2005

Involvement of spinal cord nuclear factor kappaB activation in rat models of proinflammatory cytokine-mediated pain facilitation.

Proinflammatory cytokines, such as interleukin-1beta and tumour necrosis factor-alpha, are released by activated glial cells in the spinal cord and play a major role in pain facilitation. These cytokines exert their actions, at least partially, through the activation of the transcription factor, nuclear factor kappaB (NF-kappaB). In turn, NF-kappaB regulates the transcription of many inflammatory mediators, including cytokines. We have previously shown that intrathecal injection of the human immunodeficiency virus-1 (HIV-1) envelope glycoprotein, gp120, induces mechanical allodynia via the release of proinflammatory cytokines. Here, we investigated whether NF-kappaB is involved in gp120-induced pain behaviour in Sprague-Dawley rats. Intrathecal administration of NF-kappaB inhibitors, pyrrolidinedithiocarbamate (PDTC) and SN50, prior to gp120 partially attenuated gp120-induced allodynia. In addition, PDTC delayed and reversed allodynia in a model of neuropathic pain induced by sciatic nerve inflammation. These observations suggest that intrathecal gp120 may lead to activation of NF-kappaB within the spinal cord. To reveal NF-kappaB activation, we assessed inhibitory factor kappaBalpha (IkappaBalpha) mRNA expression by in situ hybridization, as NF-kappaB activation up-regulates IkappaBalpha gene expression as part of an autoregulatory feedback loop. No or low levels of IkappaBalpha mRNA were detected in the lumbar spinal cord of vehicle-injected rats, whereas IkappaBalpha mRNA expression was markedly induced in the spinal cord following intrathecal gp120 in predominantly astrocytes and endothelial cells. Moreover, IkappaBalpha mRNA expression positively correlated with proinflammatory cytokine protein levels in lumbosacral cerebrospinal fluid. Together, these results demonstrate that spinal cord NF-kappaB activation is involved, at least in part, in exaggerated pain states.

Animals↗

PubMed2005

Cinacalcet HCl attenuates parathyroid hyperplasia in a rat model of secondary hyperparathyroidism.

BACKGROUND: Secondary hyperparathyroidism (HPT) in chronic kidney disease (CKD) is a physiologic response to kidney failure characterized by elevated serum parathyroid hormone (PTH) levels and parathyroid gland enlargement. Calcimimetic agents acting through allosteric modification of the calcium-sensing receptor (CaR) can attenuate parathyroid hyperplasia in rats with secondary HPT. The present study explores the effects of the calcimimetic cinacalcet HCl on parathyroid hyperplasia, apoptosis, and PTH secretion in a rat model of secondary HPT. METHODS: Cinacalcet HCl was gavaged daily (1, 5, or 10 mg/kg) for 4 weeks starting 6 weeks post-5/6 nephrectomy. After dosing, hyperplasia was determined using parathyroid weight and proliferating cell nuclear antigen (PCNA) immunochemistry. Apoptosis was determined using in situ techniques. Serum PTH((1-34)) and blood chemistries were determined throughout the course of the study. RESULTS: Administration of cinacalcet HCl (5 or 10 mg/kg) significantly reduced the number of PCNA-positive cells and decreased parathyroid weight compared with vehicle-treated 5/6 nephrectomized rats. There was no difference in apoptosis from cinacalcet HCl-treated or vehicle-treated animals. Serum PTH and blood ionized calcium levels decreased in cinacalcet HCl-treated animals compared with vehicle-treated controls. CONCLUSION: The results confirm previous work demonstrating that calcimimetic agents attenuate the progression of parathyroid hyperplasia in subtotally nephrectomized rats, extending earlier observations to now include cinacalcet HCl. These results support a role for the CaR in regulating parathyroid cell proliferation. Therefore, cinacalcet HCl may represent a novel therapy for improving the management of secondary HPT.

Animals↗

PubMed2005

Clinicians' perspective of a training programme in syndromic management of sexually transmitted infections in Northern Tanzania.

This process evaluation study was designed to investigate clinicians' perception of a training programme on syndromic management of sexually transmitted infections (STIs) and their experiences in applying the skills learnt during the course. Out of 136 eligible course participants from Arusha and Kilimanjaro regions, Tanzania, 47 were invited to take part in the study and 40 agreed to participate (85%). The research instruments consisted of a structured interview including open- and close-ended questions, a self-administered questionnaire, and an observation checklist. While the clinicians reported to be satisfied with the course itself, the results revealed insufficient practical training. The clinicians reported problems with condom promotion and partner notification, and frequent shortage of equipment and drugs in the clinics was observed. Future courses on syndromic management of STI should focus on skills training related to health education and counselling, and have a stronger emphasis on practical, clinical work. There is need to address barriers to condom promotion and partner referral.

Health Education↗

PubMed2005

Combined minimally invasive pulmonary vein isolation, left atrial appendage excision and cardiac resynchronization therapy for heart failure: case report.

A 76-year-old male with ischemic cardiomyopathy presented with heart failure symptoms in the absence of angina. Several hospitalizations were required due to heart failure exacerbation and paroxysmal atrial fibrillation. Electrocardiography and tissue synchronization imaging confirmed ventricular dyssynchrony, requiring biventricular pacing. After a failed attempt of percutaneous placement of the left ventricular lead, a novel minimally invasive approach was indicated. It consisted of left ventricular epicardial lead placement, microwave pulmonary vein isolation, and left atrial appendage excision through bilateral minithoracotomies. The postoperative recovery was unremarkable, with reestablishment of the ventricular synchrony and regular rhythm.

Aged↗

PubMed2005

Operative laparoscopy in tubal pregnancy: preoperative ultrasonographic measurement of hemoperitoneum as a predictor of blood loss and outcome.

OBJECTIVE: To study the relationship of ultrasonographic measurement of hemoperitoneum to estimated blood loss and outcome of operative laparoscopy in ectopic pregnancy. STUDY DESIGN: Retrospective study of all tubal pregnancy patients with preoperative ultrasonographic evidence of hemoperitoneum who underwent laparoscopy as part of the procedure at a tertiary referral center over a 3.5-year period. The largest transabdominal and transvaginal measurements of pelvic fluid collections in anterior-posterior, transverse and cranial-caudal dimensions were measured from all available preoperative ultrasound films. Patient characteristics, volume of estimated blood loss and complications were reviewed. RESULTS: A total of 29 patients were included in the study. Twenty-one underwent successful laparoscopic treatment (group 1). Four patients underwent conversion from laparoscopy to laparotomy because of bleeding (group 2). Four patients underwent conversion because of adhesions (group 3). There were no significant differences in patient characteristics. The single largest ultrasonographc diameter of pelvic fluid collection in any dimension seemed to correlate with estimated blood loss volume (R2 =.659; p <0.05), with significant volume present in those with a maximum diameter > 7 cm. The mean diameter of greatest measurements was significantly different between groups 1 and 2 and between groups 2 and 3 (p<0.05). However, such measurements did not predict the success of laparosocpic surgery. CONCLUSION: The greatest ultrasonographic measurement of pelvic fluid collection > or = 7 cm in any dimension appears to serve as a marker of significant hemoperitoneum. Hemoperitoneum alone does not appear to predict the outcome of surgery, and otherfactors should be considered prior to performing operative laparoscopy in ectopic pregnancy.

Blood Loss, Surgical↗

PubMed2005

Diagnostic instrumentation aboard ISS: just-in-time training for non-physician crewmembers.

INTRODUCTION: The performance of complex tasks on the International Space Station (ISS) requires significant preflight crew training commitments and frequent skill and knowledge refreshment. This report documents a recently developed "just-in-time" training methodology, which integrates preflight hardware familiarization and procedure training with an on-orbit CD-ROM-based skill enhancement. This "just-in-time" concept was used to support real-time remote expert guidance to complete ultrasound examinations using the ISS Human Research Facility (HRF). METHODS: An American and Russian ISS crewmember received 2 h of "hands on" ultrasound training 8 mo prior to the on-orbit ultrasound exam. A CD-ROM-based Onboard Proficiency Enhancement (OPE) interactive multimedia program consisting of memory enhancing tutorials, and skill testing exercises, was completed by the crewmember 6 d prior to the on-orbit ultrasound exam. The crewmember was then remotely guided through a thoracic, vascular, and echocardiographic examination by ultrasound imaging experts. RESULTS: Results of the CD-ROM-based OPE session were used to modify the instructions during a complete 35-min real-time thoracic, cardiac, and carotid/jugular ultrasound study. Following commands from the ground-based expert, the crewmember acquired all target views and images without difficulty. The anatomical content and fidelity of ultrasound video were adequate for clinical decision making. CONCLUSIONS: Complex ultrasound experiments with expert guidance were performed with high accuracy following limited preflight training and multimedia based in-flight review, despite a 2-s communication latency. In-flight application of multimedia proficiency enhancement software, coupled with real-time remote expert guidance, facilitates the successful performance of ultrasound examinations on orbit and may have additional terrestrial and space applications.

Aerospace Medicine↗

PubMed2004

Zone design for environment and health studies using pre-aggregated data.

Many environment and health studies employ geographical areas as the units of analysis, either through choice or necessity. The design of these areas can greatly influence any observed spatial relationships or patterns-an effect known as the modifiable areal unit problem. In this paper we identify the phenomena and processes which are typically measured in environment and health studies and present a conceptualisation for their representation as data objects in spatial analysis. We discuss the circumstances under which we find ourselves using areas for representation and outline the application of zone design techniques for the creation of such areas in environment and health studies. An empirical study of the relationship between deprivation and limiting long-term illness in the former county of Avon, UK, is employed to demonstrate the potential usefulness of zone design techniques for creating zones with stable estimates and for exploring the sensitivity of relationships to changes in the zoning system. In particular, we illustrate the inappropriateness of the 1991 Census enumeration district and ward zoning systems for such an analysis and conclude that automatically designed aggregations may be a more appropriate basis for analysis than any pre-existing zoning system.

Adolescent↗

PubMed2004

GOToolBox: functional analysis of gene datasets based on Gene Ontology.

We have developed methods and tools based on the Gene Ontology (GO) resource allowing the identification of statistically over- or under-represented terms in a gene dataset; the clustering of functionally related genes within a set; and the retrieval of genes sharing annotations with a query gene. GO annotations can also be constrained to a slim hierarchy or a given level of the ontology. The source codes are available upon request, and distributed under the GPL license.

Animals↗

PubMed2004

SPOTS: signaling protein oligomeric transduction structures are early mediators of death receptor-induced apoptosis at the plasma membrane.

Fas (CD95, APO-1, TNFRSF6) is a TNF receptor superfamily member that directly triggers apoptosis and contributes to the maintenance of lymphocyte homeostasis and prevention of autoimmunity. Although FADD and caspase-8 have been identified as key intracellular mediators of Fas signaling, it is not clear how recruitment of these proteins to the Fas death domain leads to activation of caspase-8 in the receptor signaling complex. We have used high-resolution confocal microscopy and live cell imaging to study the sequelae of early events in Fas signaling. These studies have revealed a new stage of Fas signaling in which receptor ligation leads to the formation of surface receptor oligomers that we term signaling protein oligomerization transduction structures (SPOTS). Formation of SPOTS depends on the presence of an intact Fas death domain and FADD but is independent of caspase activity. Analysis of cells expressing Fas mutations from patients with the autoimmune lymphoproliferative syndrome (ALPS) reveals that formation of SPOTS can be disrupted by distinct mechanisms in ALPS.

Animals↗

PubMed2004

Evaluation of shoulder integrity in space: first report of musculoskeletal US on the International Space Station.

Investigative procedures were approved by Henry Ford Human Investigation Committee and NASA Johnson Space Center Committee for Protection of Human Subjects. Informed consent was obtained. Authors evaluated ability of nonphysician crewmember to obtain diagnostic-quality musculoskeletal ultrasonographic (US) data of the shoulder by following a just-in-time training algorithm and using real-time remote guidance aboard the International Space Station (ISS). ISS Expedition-9 crewmembers attended a 2.5-hour didactic and hands-on US training session 4 months before launch. Aboard the ISS, they completed a 1-hour computer-based Onboard Proficiency Enhancement program 7 days before examination. Crewmembers did not receive specific training in shoulder anatomy or shoulder US techniques. Evaluation of astronaut shoulder integrity was done by using a Human Research Facility US system. Crew used special positioning techniques for subject and operator to facilitate US in microgravity environment. Common anatomic reference points aided initial probe placement. Real-time US video of shoulder was transmitted to remote experienced sonologists in Telescience Center at Johnson Space Center. Probe manipulation and equipment adjustments were guided with verbal commands from remote sonologists to astronaut operators to complete rotator cuff evaluation. Comprehensive US of crewmember's shoulder included transverse and longitudinal images of biceps and supraspinatus tendons and articular cartilage surface. Total examination time required to guide astronaut operator to acquire necessary images was approximately 15 minutes. Multiple arm and probe positions were used to acquire dynamic video images that were of excellent quality to allow evaluation of shoulder integrity. Postsession download and analysis of high-fidelity US images collected onboard demonstrated additional anatomic detail that could be used to exclude subtle injury. Musculoskeletal US can be performed in space by minimally trained operators by using remote guidance. This technique can be used to evaluate shoulder integrity in symptomatic crewmembers after strenuous extravehicular activities or to monitor microgravity-associated changes in musculoskeletal anatomy. Just-in-time training, combined with remote experienced physician guidance, may provide a useful approach to complex medical tasks performed by nonexperienced personnel in a variety of remote settings, including current and future space programs.

Humans↗

PubMed2004

The calcium-sensing receptor: a key factor in the pathogenesis of secondary hyperparathyroidism.

Serum calcium levels are regulated by the action of parathyroid hormone (PTH). Major drivers of PTH hypersecretion and parathyroid cell proliferation are the hypocalcemia and hyperphosphatemia that develop in chronic kidney disease patients with secondary hyperparathyroidism (SHPT) as a result of low calcitriol levels and decreased kidney function. Increased PTH production in response to systemic hypocalcemia is mediated by the calcium-sensing receptor (CaR). Furthermore, as SHPT progresses, reduced expression of CaRs and vitamin D receptors (VDRs) in hyperplastic parathyroid glands may limit the ability of calcium and calcitriol to regulate PTH secretion. Current treatment for SHPT includes the administration of vitamin D sterols and phosphate binders. Treatment with vitamin D is initially effective, but efficacy often wanes with further disease progression. The actions of vitamin D sterols are undermined by reduced expression of VDRs in the parathyroid gland. Furthermore, the calcemic and phosphatemic actions of vitamin D mean that it has the potential to exacerbate abnormal mineral metabolism, resulting in the formation of vascular calcifications. Effective new treatments for SHPT that have a positive impact on mineral metabolism are clearly needed. Recent research shows that drugs that selectively target the CaR, calcimimetics, have the potential to meet these requirements.

Calcium↗

PubMed2004

Distance, rurality and the need for care: access to health services in South West England.

BACKGROUND: This paper explores the geographical accessibility of health services in urban and rural areas of the South West of England, comparing two measures of geographical access and characterising the areas most remote from hospitals.Straight-line distance and drive-time to the nearest general practice (GP) and acute hospital (DGH) were calculated for postcodes and aggregated to 1991 Census wards. The correlation between the two measures was used to identify wards where straight-line distance was not an accurate predictor of drive-time. Wards over 25 km from a DGH were classified as 'remote', and characterised in terms of rurality, deprivation, age structure and health status of the population. RESULTS: The access measures were highly correlated (r2>0.93). The greatest differences were found in coastal and rural wards of the far South West. Median straight-line distance to GPs was 1 km (IQR = 0.6-2 km) and to DGHs, 12 km (IQR = 5-19 km). Deprivation and rates of premature limiting long term illness were raised in areas most distant from hospitals, but there was no evidence of higher premature mortality rates. Half of the wards remote from a DGH were not classed as rural by the Office for National Statistics. Almost a quarter of households in the wards furthest from hospitals had no car, and the proportion of households with access to two or more cars fell in the most remote areas. CONCLUSION: Drive-time is a more accurate measure of access for peripheral and rural areas. Geographical access to health services, especially GPs, is good, but remoteness affects both rural and urban areas: studies concentrating purely on rural areas may underestimate geographical barriers to accessing health care. A sizeable minority of households still had no car in 1991, and few had more than one car, particularly in areas very close to and very distant from hospitals. Better measures of geographical access, which integrate public and private transport availability with distance and travel time, are required if an accurate reflection of the experience those without their own transport is to be obtained.

Journal Article↗

PubMed2004

A role for proinflammatory cytokines and fractalkine in analgesia, tolerance, and subsequent pain facilitation induced by chronic intrathecal morphine.

The present experiments examined the role of spinal proinflammatory cytokines [interleukin-1beta (IL-1)] and chemokines (fractalkine) in acute analgesia and in the development of analgesic tolerance, thermal hyperalgesia, and tactile allodynia in response to chronic intrathecal morphine. Chronic (5 d), but not acute (1 d), intrathecal morphine was associated with a rapid increase in proinflammatory cytokine protein and/or mRNA in dorsal spinal cord and lumbosacral CSF. To determine whether IL-1 release modulates the effects of morphine, intrathecal morphine was coadministered with intrathecal IL-1 receptor antagonist (IL-1ra). This regimen potentiated acute morphine analgesia and inhibited the development of hyperalgesia, allodynia, and analgesic tolerance. Similarly, intrathecal IL-1ra administered after the establishment of morphine tolerance reversed hyperalgesia and prevented the additional development of tolerance and allodynia. Fractalkine also appears to modulate the effects of intrathecal morphine because coadministration of morphine with intrathecal neutralizing antibody against the fractalkine receptor (CX3CR1) potentiated acute morphine analgesia and attenuated the development of tolerance, hyperalgesia, and allodynia. Fractalkine may be exerting these effects via IL-1 because fractalkine (CX3CL1) induced the release of IL-1 from acutely isolated dorsal spinal cord in vitro. Finally, gene therapy with an adenoviral vector encoding for the release of the anti-inflammatory cytokine IL-10 also potentiated acute morphine analgesia and attenuated the development of tolerance, hyperalgesia, and allodynia. Taken together, these results suggest that IL-1 and fractalkine are endogenous regulators of morphine analgesia and are involved in the increases in pain sensitivity that occur after chronic opiates.

Analgesics, Opioid↗

PubMed2004

Effectiveness of early implantation of cardioverter defibrillator for postoperative ventricular tachyarrhythmia.

The effectiveness of implantable cardioverter defibrillators (ICDs) implanted in the early postoperative period after cardiac surgery for ventricular tachyarrhythmias is unknown, because all of the major trials excluded this patient population. Thus, a 10-year retrospective study was conducted of patients who had ICDs implanted for de novo postoperative ventricular tachyarrhythmias during the index admission for cardiac surgery. There was a high rate of early recurrence of ventricular tachyarrhythmia treated by defibrillators, and this finding questions the exclusion of this important patient population from large trials.

Aged↗

PubMed2004

Pulmonary vein antrum isolation for treatment of atrial fibrillation in patients with valvular heart disease or prior open heart surgery.

OBJECTIVES: The goal of this study was to assess the safety and efficacy of pulmonary vein antrum isolation in patients with moderate valvular heart disease or open-heart surgery and atrial fibrillation (AF). BACKGROUND: Valvular heart disease and open-heart surgery are commonly associated with AF and increase the risk of adverse events in AF patients. METHODS: A total of 391 consecutive patients who had pulmonary vein antrum isolation performed between December 2000 and December 2002 were screened. A total of 142 of these patients had clinically significant valvular disease or prior cardiac surgery. End points included AF recurrence and pulmonary vein antrum isolation complication rates. RESULTS: Patients with valvular heart disease or prior open-heart surgery were older, had larger left atria and a more advanced New York Heart Association class. They did not differ significantly with respect to gender, but had a longer history of AF. Procedure times were similar between patients with and without valvular heart disease or prior open-heart surgery. After 18 +/- 7 months in the lone AF patients, 11 +/- 5 months in patients with valvular heart disease, and 10 +/- 5 months in patients with prior open heart surgery, there was a trend toward lower recurrence of AF in patients with lone AF who enjoyed a 98% overall cure rate after up to 2 pulmonary vein antrum isolations versus 93% among patients with valvular heart disease (P = .04) and prior open heart surgery (P = .07). Complication rates were comparable between groups. CONCLUSIONS: Pulmonary vein antrum isolation is safe and effective in patients with moderate valvular heart disease and the patients who developed AF after open-heart surgery. These results have implications for our understanding of the pathophysiology of AF in patients with moderate valvular heart disease or past cardiac surgery and should be considered when discussing treatment options in these patients.

Atrial Fibrillation↗

PubMed2004

Snake venom phospholipase A2s (Asp49 and Lys49) induce mechanical allodynia upon peri-sciatic administration: involvement of spinal cord glia, proinflammatory cytokines and nitric oxide.

Snakebites constitute a serious public health problem in Central and South America, where species of the lancehead pit vipers (genus Bothrops) cause the majority of accidents. Bothrops envenomations are very painful, and this effect is not neutralized by antivenom treatment. Two variants of secretory phospholipases A2 (sPLA2), corresponding to Asp49 and Lys49 PLA2s, have been isolated from Bothrops asper venom. These sPLA2s induce hyperalgesia in rats following subcutaneous injection. However, venom in natural Bothrops bites is frequently delivered intramuscularly, thereby potentially reaching peripheral nerve bundles. Thus, the present series of experiments tested whether these sPLA2s could exert pain-enhancing effects following administration around healthy sciatic nerve. Both were found to produce mechanical allodynia ipsilateral to the injection site; no thermal hyperalgesia was observed. As no prior study has examined potential spinal mechanisms underlying sPLA2 actions, a series of anatomical and pharmacological studies were performed. These demonstrated that both sPLA2s produce activation of dorsal horn astrocytes and microglia that is more prominent ipsilateral to the site of injection. As proinflammatory cytokines and nitric oxide have each been previously implicated in spinally mediated pain facilitation, the effect of pharmacological blockade of these substances was tested. The results demonstrate that mechanical allodynia induced by both sPLA2s is blocked by interleukin-1 receptor antagonist, anti-rat interleukin-6 neutralizing antibody, the anti-inflammatory cytokine interleukin-10, and a nitric oxide synthesis inhibitor (L-NAME). As a variety of immune cells also produce and release sPLA2s during inflammatory states, the data may have general implications for the understanding of inflammatory pain.

Animals↗

PubMed2004

HIV-1 gp120 stimulates proinflammatory cytokine-mediated pain facilitation via activation of nitric oxide synthase-I (nNOS).

It has become clear that spinal cord glia (microglia and astrocytes) importantly contribute to the creation of exaggerated pain responses. One model used to study this is peri-spinal (intrathecal, i.t.) administration of gp120, an envelope protein of HIV-1 known to activate glia. Previous studies demonstrated that i.t. gp120 produces pain facilitation via the release of glial proinflammatory cytokines. The present series of studies tested whether spinal nitric oxide (NO) contributes to i.t. gp120-induced mechanical allodynia and, if so, what effect NO has on spinal proinflammatory cytokines. gp120 stimulation of acutely isolated lumbar dorsal spinal cords released NO as well as proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta (IL1), interleukin-6 (IL6)), thus identifying NO as a candidate mediator of gp120-induced behavioral effects. Behaviorally, identical effects were observed when gp120-induced mechanical allodynia was challenged by i.t. pre-treatment with either a broad-spectrum nitric oxide synthase (NOS) inhibitor (L-NAME) or 7-NINA, a selective inhibitor of NOS type-I (nNOS). Both abolished gp120-induced mechanical allodynia. While the literature pre-dominantly documents that proinflammatory cytokines stimulate the production of NO rather than the reverse, here we show that gp120-induced NO increases proinflammatory cytokine mRNA levels (RT-PCR) and both protein expression and protein release (serial ELISA). Furthermore, gp120 increases mRNA for IL1 converting enzyme and matrix metalloproteinase-9, enzymes responsible for activation and release of proinflammatory cytokines.

Animals↗

PubMed2004

Peri-sciatic proinflammatory cytokines, reactive oxygen species, and complement induce mirror-image neuropathic pain in rats.

In inflammatory neuropathy, immune activation near intact peripheral nerves induces mechanical allodynia. The identity of the peripheral immune product(s) that lead to these changes in pain behavior is unknown. The present series of studies utilized the sciatic inflammatory neuropathy (SIN) model to examine this question. Here, inflammatory neuropathy is created by injecting an immune activator (zymosan) around one sciatic nerve via an indwelling catheter. Our prior studies demonstrated that peri-sciatic zymosan activated macrophages and neutrophils to release proinflammatory cytokines and reactive oxygen species (ROS). In addition, zymosan is a classical activator of the complement cascade. Thus the present series of experiments examined whether any of these inflammatory mediators are involved in the initial induction of SIN-induced ipsilateral or bilateral allodynias. Peri-sciatic injection of selective inhibitors/antagonists revealed that a number of immune products are early mediators of the resultant allodynias, including proinflammatory cytokines (tumor necrosis factor, interleukin-1, and interleukin-6), ROS, and complement. Thus these immune-derived substances can markedly alter sensory nerve function at mid-axon.

Animals↗