Arterial Wall Stiffening in Caveolin-1 Deficiency-Induced Pulmonary Artery Hypertension in Mice.

BACKGROUND: Pulmonary artery hypertension (PAH) is a complex disorder that can lead to right heart failure. The generation of caveolin-1 deficient mice (CAV-1-/-) has provided an alternative genetic model to study the mechanisms of pulmonary hypertension. However, the vascular adaptations in these mice have not been characterized. OBJECTIVE: To determine the histological and functional changes in the pulmonary and carotid arteries in CAV-1-/- induced PAH. METHODS: Pulmonary and carotid arteries of young (4-6 months old) and mature (9-12 months old) CAV-1-/- mice were tested and compared to normal wild type mice. RESULTS: Artery stiffness increases in CAV-1-/- mice, especially the circumferential stiffness of the pulmonary arteries. Increases in stiffness were quantified by a decrease in circumferential stretch and transition strain, increases in elastic moduli, and an increase in total strain energy at physiologic strains. Changes in mechanical properties for the pulmonary artery correlated with increased collagen content while carotid artery mechanical properties correlated with decreased elastin content. CONCLUSIONS: We demonstrated that an increase in artery stiffness is associated with CAV-1 deficiency-induced pulmonary hypertension. These results improve our understanding of artery remodeling in PAH.

Disc degeneration induces a mechano-sensitization of disc afferent nerve fibers that associates with low back pain.

OBJECTIVE: We aimed to investigate mechano-sensitivity at the afferent nerve fibers projecting to degenerated intervertebral disc (IVD) and nociceptive behaviour in a rat model of low back pain (LBP). DESIGN: Animal model with LBP was established by lumbar 4/5 IVD puncture and nucleus pulposus aspiration. In vivo single nerve recordings (n = 121) were introduced to measure discharge frequency at the afferent nerve fiber innervating the IVD during mechanical stimulations (von Frey filament or intradiscal pressure). Nerve growth factor (NGF) expression levels in the IVD (n = 20) were assessed by Western blot. LBP-related behaviour (n = 22) was assessed by measuring changes in rearing, mechanical paw-withdrawal threshold, and dynamic weight bearing in a freely walking rat. Inhibitory effect of morphine on the neuronal excitability (n = 19) and painful behaviour (n = 28) was also assessed. RESULTS: Compared to those with sham or naïve IVD, animal group with degenerated IVD displayed the sensitized neuronal responses and painful behaviour, with hyperexcitability of the afferent nerve fibers in any range of mechanical stimulations (von Frey filament stimulation; 1, 2, and 26 g; intradiscal pressure, 1,500-3,000 mm Hg), strong upregulation of NGF (200-250 % increase), and LBP-like behaviour such as failure of rearing, front limbs-dependent walking pattern, and hypersensitivity in hind-paws. However, the neuronal hyperexcitability and pain behaviour were attenuated after local (30 µM) or systemic (3 mg kg-1) morphine administration. CONCLUSIONS: Our study suggests that enhanced mechano-sensitivity at the afferent nerve fiber innervating degenerated IVD is deeply correlated with LBP development, which supports the hypothesis that hyperexcited responses at the nerve fibers represent a decisive source of LBP.

Anti-inflammatory effect of low intensity ultrasound (LIUS) on complete Freund's adjuvant-induced arthritis synovium.

OBJECTIVES: Arthritis with intra-articular inflammation was accompanied by joint pain, swelling, and stiffness leading to significant functional impairment. Thus, regulation of joint inflammation is a good therapeutic approach for patients with arthritis. In this study, the effect of low intensity ultrasound (LIUS) applied to an adjuvant-induced arthritic rat model on the synovium was investigated. DESIGN: Synovial inflammation was induced by complete Freund's adjuvant (CFA)-injection into the rat knee joint. LIUS (200 mW/cm(2)) was applied on the ipsilateral knee everyday for 10 min beginning 1 day after inflammation induction. The expression of proinflammatory factors and immunohistochemical staining pattern of the synovium were assessed. RESULTS: CFA induced an increase of the knee circumference that was significantly diminished by LIUS. Synovial membrane hyperplasia in the ipsilateral joint was also affected by LIUS. The inflammatory mediators, COX-1/2, IL-1ß, and iNOS, but not TNF-α, in the synovial membrane were induced after 3 days, and they closely correlated with the degree of edema. In the synovial membrane, the expression of inflammatory mediators was reduced by LIUS. The chemoattractant chemokine receptor CCR5 also was involved. On immunohistochemical analysis, CFA caused increased infiltration of CD11b-positive cells in the synovium. After 3 days, neutrophils, myeloperoxidase (MPO)-positive cells filled the inflammatory core; later, monocytes and macrophages, ionized calcium binding adaptor molecule 1 (Iba1)-positive cells in the periphery infiltrated the core by day 5. LIUS markedly reduced CFA-induced inflammatory cells infiltration. CONCLUSION: LIUS showed a potent anti-inflammatory effect in this animal arthritis model with reduced infiltration of inflammatory cells into the synovium.

Prognostic significance of thymidylate synthase, dihydropyrimidine dehydrogenase and thymidine phosphorylase protein expression in colorectal cancer patients treated with or without 5-fluorouracil-based chemotherapy.

BACKGROUND: Low tumour expression levels of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and thymidine phosphorylase (TP) have been linked with improved outcome for colorectal cancer (CRC) patients treated with 5-fluorouracil (5-FU). It is unclear whether this occurs because such tumours have better prognosis or they are more sensitive to 5-FU treatment. PATIENTS AND METHODS: Associations between TS, DPD and TP levels, determined by tissue microarrays and immunohistochemistry, and survival was evaluated in 945 CRC patients according to treatment status. RESULTS: Low TS and DPD expression associated with worse prognosis in stage II [hazard ratio (HR) = 1.69, 95% confidence interval (CI) (1.09-2.63) and HR = 1.92 (95% CI 1.23-2.94), respectively] and stage III CRC patients treated by surgery alone [HR = 1.39 (95% CI 0.92-2.13) and HR = 1.49 (95% CI 1.02-2.17), respectively]. Low TS, DPD and TP associated with trends for better outcome in stage III patients treated with 5-FU [HR = 0.81 (95% CI 0.49-1.33), HR = 0.70 (95% CI 0.42-1.15) and HR = 0.66 (95% CI 0.39-1.12), respectively]. CONCLUSION: Low TS and DPD expression are prognostic for worse outcome in CRC patients treated by surgery alone, whereas low TS, DPD and TP expression are prognostic for better outcome in patients treated with 5-FU chemotherapy. These results provide indirect evidence that low TS, DPD and TP protein expression are predictive of good response to 5-FU chemotherapy.

Cost-effective screening for urinary tract infections in urogynaecological patients.

This study aims to test the cost-effectiveness of reagent-strip urine nitrite compared with microbiological laboratory testing for screening of urinary tract infections (UTI). The study is a retrospective review of 708 female patients who underwent cystometry during a 1-year period. Urine dipstick nitrite was used as a screening test for UTI while urine cultures were taken as an outcome. Symptoms of UTI were noted. Of 708 patients screened, 70 (9.9%) had a significant UTI. Only 32 (4.5%)of 708 patients were nitrite positive. Urine dipstick nitrite has sensitivity of 40%, specificity of 99%, positive predictive value (PPV) of 88 % and negative predictive value (NPV) of 94%. If the screening test included symptoms for UTI together with urine nitrite, the results are: sensitivity 89%, specificity 31%, PPV 12% and NPV 96%. A combination of screening with urine nitrite and UTI symptoms can increase sensitivity to 89%. A total of 29% of specimens (screen negative=nitrite negative/asymptomatic) can then be excluded from UFEME/culture testing, thus resulting in cost savings.

Tissue microarrays characterise the clinical significance of a VEGF-A protein expression signature in gastrointestinal stromal tumours.

A tissue microarray analysis of 22 proteins in gastrointestinal stromal tumours (GIST), followed by an unsupervised, hierarchical monothetic cluster statistical analysis of the results, allowed us to detect a vascular endothelial growth factor (VEGF) protein overexpression signature discriminator of prognosis in GIST, and discover novel VEGF-A DNA variants that may have functional significance.

Epithelial-mesenchymal interactions in keloid pathogenesis modulate vascular endothelial growth factor expression and secretion.

Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis during the wound healing process. As epithelial-mesenchymal interactions have been shown to regulate a plethora of genes in wound healing, we hypothesized that these interactions might have a role in modulating VEGF expression and angiogenesis. A two chamber co-culture model was used, wherein normal and keloid keratinocytes and fibroblasts were physically separated by membrane inserts while allowing cytokine diffusion. Cell lysates obtained from keratinocytes co-cultured with fibroblasts demonstrated increased expression of VEGF. An enzyme-linked immunosorbent assay (ELISA) showed significant increase in VEGF expression in co-culture conditioned media compared with controls. Additionally, the conditioned medium from keloid keratinocyte and fibroblast co-cultures increased proliferation and formation of complex three-dimensional capillary-like structures in human umbilical vein endothelial cells, emphasising the importance of epithelial-mesenchymal interactions in the angiogenic process. Immunostaining of keloid tissue localized VEGF in the basal layer of the epidermis and also demonstrated higher blood vessel density than normal skin. Keloid tissue extract also demonstrated increased expression of VEGF compared with normal skin. It is likely that epidermal VEGF exerts significant paracrine control over the dynamics and expression profile of underlying dermal fibroblasts. Addition of the inhibitors WP631, mitoxantrone, and Rapamycin to keloid keratinocyte and fibroblast co-cultures, downregulated secreted VEGF expression in a dose-dependent manner, suggesting therapeutic potential for these compounds in the treatment of keloid scars.

RUNX3 protein is overexpressed in human basal cell carcinomas.

Basal cell carcinomas (BCC), which are the most common form of skin malignancy, are invariably associated with the deregulation of the Sonic Hedgehog (Shh) signalling pathway. As such, BCC represent a unique model for the study of interactions of the Shh pathway with other genes and pathways. We constructed a tissue microarray (TMA) of 75 paired BCC and normal skin and analysed the expression of beta-catenin and RUNX3, nuclear effectors of the wingless-Int (Wnt) and bone morphogenetic protein/transforming growth factor-beta pathways, respectively. In line with previous reports, we observed varying subcellular expression pattern of beta-catenin in BCC, with 31 cases (41%) showing nuclear accumulation. In contrast, all the BCC cases tested by the TMA showed RUNX3 protein uniformly overexpressed in the nuclei of the cancer cells. Analysis by Western blotting and DNA sequencing indicates that the overexpressed protein is normal and full-length, containing no mutation in the coding region, implicating RUNX3 as an oncogene in certain human cancers. Our results indicate that although the deregulation of Wnt signalling could contribute to the pathogenesis of a subset of BCC, RUNX3 appears to be a universal downstream mediator of a constitutively active Shh pathway in BCC.

The relation between viable segments and left ventricular ejection fraction improvement.

For patients with coronary artery disease and left ventricular dysfunction who undergo revascularization, it is important to estimate the left ventricular ejection fraction (LVEF) improvement after revascularization, as this is a strong indicator of the long-term outcome. Identification of viable segments from echocardiography has been considered a predictive sign of LVEF improvement. However, a quantitative relation between segmental function recovery and global ejection fraction improvement has not been established. There is a clinical need to determine parameters that are predictive to LVEF improvement. A cylindrical left ventricular model is proposed to establish the relation between segmental myocardial function and LVEF based on a 12-segment echocardiograph model. Model results show that LVEF improvement is directly related to the contraction ratio in normal segments and a weighted sum of the number of viable segments that recover to normal or hypokinetic, which is equal to a weighted sum of the change in wall motion scores. This new combined parameter is a better predictor of the amount of LVEF improvement than the total number of viable segments or preoperative ejection fraction. The predictive value of the model was illustrated in a group of four patients with coronary artery disease who underwent revascularization.

Apoptosis induction by 4beta-acetoxyscirpendiol from Paecilomyces tenuipes in human leukaemia cell lines.

The carpophores of Paecilomyces tenuipes are known in the Orient for their strong antitumor activity. In continuation of our study on acetoxyscirpendiol (ASD, 4beta-acetoxyscirpene-3alpha,15-diol) as a cytotoxic component from this fungus, we report particularly on the mode of action of ASD in inducing apoptosis in human MOLT-4, THP-1 and Jurkat T cell leukaemia in vitro. The antiproliferative effects of ASD seem attributable to its induction of apoptosis in the cells, as it blocked the cell cycle, induced hypodiploidity and bound annexin V and also cleaved poly-(ADP-ribose) polymerase (PARP) in these cell lines. The 50% inhibitory concentrations (IC50) of ASD on MOLT-4, THP-1 and Jurkat T cells were found to be 60, 85 and 60 ng/ml, respectively. ASD arrested the cell cycle at the G1/S transition and showed hypodiploidity due to the accumulation of sub-G0 population. Annexin V binding was increased in the presence of ASD in the MOLT-4 cell line in a time-dependent manner. ASD and three of its derivatives also induced cleavage of PARP in both MOLT-4 and Jurkat T cell lines. From these data, it is suggested that ASD exerts its cytotoxic activity by inducing apoptosis in leukaemia cell lines in vitro.

Burch colposuspension: review of perioperative complications at a women's and children's hospital in Singapore.

INTRODUCTION: This study aims to determine perioperative complications of Burch colposuspension. MATERIALS AND METHODS: A retrospective casenote review was conducted on all cases of Burch colposuspension performed or supervised by a single, trained urogynaecologist between January 1998 and December 2001. RESULTS: Of the 250 women, 151 (60.4%) had Burch colposuspension in conjunction with other procedures. The other procedures included 117 hysterectomies, 15 sacrocolpopexies and hysterectomies, 11 sacrocolpopexies, 4 sacrohysteropexies, 3 posterior repairs and 1 ovarian cystectomy. Data from the 99 women who underwent only Burch colposuspension were analysed. Eight (8.1%) women had blood loss of > 500 mL; of these 3 lost > 1000 mL. Three (3%) women required blood transfusion. Urinary retention occurred in 13 (13.1%) women for > 10 days and 4 (4%) women required catheterisation for between 21 and 29 days. Wound infection/haematoma, gross haematuria and febrile illness accounted for 2 (2%), 20 (20.2%) and 6 (6%) cases, respectively. One (1%) woman, who had 3 previous pelvic surgeries, required reoperation for repair of ureteric injury. CONCLUSION: Burch colposuspension should be performed or supervised by trained instructors who must anticipate potential problems, especially in women with previous pelvic surgeries, before they get worse. There should be strict criteria of the number of Burch colposuspension observed and assisted, before performing them supervised.

Quantitative prediction of improvement in cardiac function after revascularization with MR imaging and modeling: initial results.

PURPOSE: To evaluate a model that can be used quantitatively to predict changes in postrevascularization left ventricular function based on classification of myocardial tissue as hibernating, scarred, or normal with cine magnetic resonance (MR) imaging. MATERIALS AND METHODS: Eleven patients with chronic left ventricular dysfunction were studied before and after revascularization with cine MR imaging. Regional myocardial contractility and wall thickness were used in the model to predict postrevascularization ejection fraction (EF). The actual EF from the postrevascularization MR images was compared with the EF from the prerevascularization images predicted with the model by using regression analysis and Bland-Altman analysis. RESULTS: Correlation between the actual EF after revascularization and the EF predicted by using the model yielded an R value of 0.98, with a standard error of 1.3 EF percentage points. Predicting changes in function in a myocardial segment was less successful because only 55% of segments classified as hibernating actually improved resting function after revascularization. In nonimproved segments, 78% were either adjacent to infarcted segments or had nontransmural wall thinning. CONCLUSION: A simple mathematical model combined with functional information provided by MR imaging was used to predict improvements in global EF resulting from revascularization.

A novel method for convenient assessment of arthritic pain in voluntarily walking rats.

Quantification of arthritic pain can be very useful in elucidating the mechanisms of arthritis and in assessing the effect of anti-arthritic medication or treatment. Here we report a novel method that allows convenient measurements of the severity of arthritic pain in voluntarily walking rats. We constructed a device to measure the weight load on each leg while the animal was walking through a path, the bottom of which was equipped with strain gauge weight sensors. Using this device, we measured the weight load on the right hind leg before and after induction of arthritis by carrageenan injection into the knee joint cavity of this leg. The carrageenan injection resulted in a significant reduction of weight load on the affected leg; the load decreased to the minimum level at 4 h after the injection and gradually returned to the pre-injection level by the fifth day. Intraperitoneal administration of morphine at 5.5 h after carrageenan injection could reverse the weight load change. These results suggest that our new device is an effective tool for convenient measurements of arthritic pain in dynamic conditions like walking.

Contractile responses in arteries subjected to hypertensive pressure in seven-day organ culture.

Early stage changes in hypertensive arteries have a significant effect on the long-term adaptation of the arteries. Compared to the long-term adaptation, little is known about the early dimensional and functional changes in hypertensive arteries in the first few days of hypertension. To study the early stage changes in hypertensive arteries, porcine common carotid arteries were cultured for seven days in a simplified ex vivo artery organ culture system with pulsatile flow under hypertensive (200+/-30 mm Hg) or normotensive (100+/-20 mm Hg) pressure conditions while maintaining a physiological mean wall shear stress of 15 dyn/cm2. Vessel viability was demonstrated by contractile diameter responses to norepinephrine (NE), carbachol (CCh), and sodium nitroprusside (SNP) as well as staining for mitochondrial activity and cell apoptosis/necrosis. The results show that arteries demonstrated strong contractile responses to NE, CCh, and SNP, basal tone, and viable mitochondria in the organ culture system for seven days. Hypertensive arteries demonstrated a stronger contractile response than normotensive arteries (p<0.05). Diameter enlargement was observed in hypertensive arteries as compared to arteries cultured under normotensive conditions. In conclusion, the pulsatile culture system can maintain arteries viable with active vasomotion tone for up to seven days. Hypertensive pressure causes arterial adaptation by significantly increasing arterial diameter and contractile response within the first seven days.

Substance p plays a critical role in photic resetting of the circadian pacemaker in the rat hypothalamus.

Glutamate is considered to be the primary neurotransmitter in the retinohypothalamic tract (RHT), which delivers photic information from the retina to the suprachiasmatic nucleus (SCN), the locus of the mammalian circadian pacemaker. However, substance P (SP) also has been suggested to play a role in retinohypothalamic transmission. In this study, we sought evidence that SP from the RHT contributes to photic resetting of the circadian pacemaker and further explored the possible interaction of SP with glutamate in this process. In rat hypothalamic slices cut parasagittally, electrical stimulation of the optic nerve in early and late subjective night produced a phase delay (2.4 +/- 0.5 hr; mean +/- SEM) and advance (2.6 +/- 0.3 hr) of the circadian rhythm of SCN neuronal firing activity, respectively. The SP antagonist L-703,606 (10 microm) applied to the slices during the nerve stimulation completely blocked the phase shifts. Likewise, a cocktail of NMDA (2-amino-5-phosphonopentanoic acid, 50 microm) and non-NMDA (6,7-dinitroquinoxaline-2,3-dione, 10 microm) antagonists completely blocked the shifts. Exogenous application of SP (1 microm) or glutamate (100 microm) to the slices in early subjective night produced a phase delay ( approximately 3 hr) of the circadian firing activity rhythm of SCN neurons. Coapplication of the NMDA and non-NMDA antagonist cocktail (as well as L-703,606) resulted in a complete blockade of the SP-induced phase delay, whereas L-703,606 (10 microm) had no effect on the glutamate-induced delay. These results suggest that SP, as well as glutamate, has a critical role in photic resetting. Furthermore, the results suggest that the two agonists act in series, SP working upstream of glutamate.

Characteristics of ectopic discharges in a rat neuropathic pain model.

Injured afferent neurons produce spontaneous activity that is generated away from the normal impulse generation site. Since this activity, referred to as ectopic discharges, may play a significant role in neuropathic pain, it is important to systematically analyze the activity in various pain states. The present study used the segmental spinal nerve injury model of neuropathic pain to quantify the ectopic discharges from injured afferents in the neuropathic rat under various conditions. All aspects of measured ectopic discharges declined as postoperative time lengthened. Neuropathic pain behaviors declined in a similar fashion over the same time period. Surgical sympathectomy on neuropathic animals lowered the level of ectopic discharges along with neuropathic pain behaviors. The data indicate that the level of ectopic discharges is well correlated with that of pain behaviors in a rat neuropathic pain model, and this reinforces the supposition that ectopic discharges are important to the maintenance of neuropathic pain behaviors. The data suggest that there are two components of ectopic discharge generator mechanisms: sympathetically dependent and sympathetically independent components.

Electrophysiological evidence for the role of substance P in retinohypothalamic transmission in the rat.

The retinohypothalamic tract (RHT) is a neural pathway through which photic time cues are delivered directly to the mammalian circadian pacemaker in the suprachiasmatic nucleus (SCN). Although the excitatory amino acid glutamate is the primary neurotransmitter in the RHT, other substances such as substance P (SPq also have been suggested to play a role. The present study tested the hypothesis that SP participates in retinohypothalamic transmission and selectively modulates either N-methyl-D-aspartate (NMDA) or non-NMDA receptor-mediated neurotransmission. The SP antagonist L-703,606 depressed the excitatory postsynaptic current (EPSC) evoked by optic nerve stimulation in SCN neurons in rat hypothalamic slices. The SP antagonist also had a similar depressive effect on the NMDA and non-NMDA receptor-mediated components of the EPSC. These results suggest that SP is an excitatory neuromodulator contributing to the expression of both the NMDA and non-NMDA receptor-mediated components of retinohypothalamic transmission.

Some membrane property changes following axotomy in A delta-type DRG cells are related to cold allodynia in rat.

Numerous studies have suggested that changes in electrophysiological properties of primary sensory neurons after axonal injury contribute to the generation of neuropathic pain. Presently, however, it is unclear which of the changes is important. To address this issue, we performed behavioral and electrophysiological experiments in a double-blind fashion; we made intracellular recordings in the S1 dorsal root ganglia excised from rats exhibiting cold allodynia behavior after chronic S1 spinal nerve transaction (allodynia-positive group) and from rats lacking such behavior after the same nerve injury (allodynia-negative group) or sham injury (sham group). In this study, we sought which of the membrane property changes produced by the spinal nerve injury in each of C-, Adelta- and Aalpha/beta-cell populations was unique to the allodynia-positive group. Analyses of our data revealed that only some changes in Adelta-cells (e.g. the decrease in resting membrane potential and in the threshold of central process) were more pronounced in or unique to the allodynia-positive group. We concluded that certain membrane property changes in the somata and dorsal root axons of Adelta-cells might be important in the generation of cold allodynia.

Cell type-specific changes of the membrane properties of peripherally-axotomized dorsal root ganglion neurons in a rat model of neuropathic pain.

Recent evidence indicates that neuropathic pain from partial peripheral nerve injury is maintained by electrophysiologically abnormal signals from injured sensory neurons. To gain an insight into the mechanisms underlying this electrophysiological abnormality, we examined the effects of S1 spinal nerve transection on the membrane properties of S1 dorsal root ganglion neurons one to two weeks after injury. This injury produced significant action potential broadening [40% (1 ms) in C-, 149% (1.5 ms) in A delta- and 84% (0.5 ms) in A alpha/beta-cells], which was primarily due to the enhancement of the "shoulder" appearing on the falling phase of the action potential in C- and A delta-cells and the emergence of a shoulder in A alpha/beta-cells, and significant cell-type specific changes in the time-course of the rising phase of the action potential; i.e. an increase in rise time (A delta: 35%, 0.15 ms; A alpha/beta: 13%, 0.04 ms) and a decrease in the maximal rate of rise (A delta: 17%, 77 V/s; A alpha/beta: 13%, 79 V/s). In addition, the nerve injury led to a significant reduction of the rheobase, an index of neuronal excitability, in all types of cells (by 41% in C-, 71% in A delta- and 59% in A alpha/beta-cells). The reduction of rheobase in A-cells was associated with a concomitant increase in apparent input resistance (by 269% in A delta- and 192% in A alpha/beta-cells), which was measured near the resting membrane potential. By contrast, the rheobase reduction in C-cells was associated with a concurrent depolarizing shift (approximately 4 mV) of the resting membrane potential. The nerve injury-induced reduction of rheobase was not accompanied by related change in input resistance or threshold potential in any of the cell populations. The present results indicate that chronic peripheral axotomy of dorsal root ganglion neurons, which gives rise to neuropathic pain, produces profound changes in the action potential waveform of dorsal root ganglion neurons in a cell type-specific fashion. Furthermore, the results suggest that the axotomy increases the excitability of dorsal root ganglion neurons not by altering input resistance (i.e. leak conductance) or threshold potential, but by increasing apparent input resistance near the resting membrane potential in A-cells and decreasing the resting membrane potential in C-cells.

Supraspinal involvement in the production of mechanical allodynia by spinal nerve injury in rats.

This study examined whether or not the production of mechanical allodynia in a rat model of neuropathic pain required an involvement of supraspinal site(s). To this aim, we assessed the effect of spinal cord section at the L1 segment level on the mechanical allodynia sign (i.e. tail flick/twitch response), which was elicited by innocuous von Frey hair stimulation of the tail after unilateral transection of the tail-innervating nerve superior caudal trunk (SCT) at the level between the S3 and S4 spinal nerves. Cord transection or hemisection of the cord ipsilateral to the injured SCT drastically (though not completely) blocked the behavioral sign of mechanical allodynia (leaving noxious pinprick-elicited tail withdrawal reflex intact), whereas sham section or contralateral hemisection of the cord was without effect. These results suggest that the generation of mechanical allodynia following partial peripheral nerve injury involves transmission of the triggering sensory signal to a site(s) rostral to the L1 segment via an ipsilateral pathway(s).