[Research advances in contact lens-associated dry eye].

Dry eye is the most common disease in ophthalmic clinics besides refractive error, which seriously affects the life quality of patients and has become an important public health problem in China. Dry eye as a kind of multifactorial disease can be induced or accelerated by contact lens wear, which is considered as one of the risk factors of dry eye. Studies have shown that the incidence of dry eye is higher in contact lens wearers than in normal people. In 2017, the Tear Film and Ocular Surface Society included contact lens-associated dry eye (CLADE) in the iatrogenic dry eye for the first time, and its importance is evident. However, ophthalmologists mostly used to focus on serious complications such as keratitis caused by contact lens wear, and CLADE has not been well valued and understood. This article reviews the latest studies on the epidemiology, pathogenesis, diagnosis, prevention, and treatment of CLADE.

Luteoloside Ameliorates Palmitic Acid-Induced in Vitro Model of Non-alcoholic Fatty Liver Disease via Activating STAT3-Triggered Hepatocyte Regeneration.

Luteoloside (Lute), a bioactive natural ingredient, widely exists in nature and possesses hepatoprotective and hepatocyte proliferation-promoting properties. This study aimed to investigate whether Lute could counteract non-alcoholic fatty liver disease (NAFLD)-caused hepatocyte damage via its stimulation of hepatocyte regeneration efficacy and to explore the involved mechanism. LO2 cells and primary hepatocytes were used to examine the hepatocyte proliferation effects of Lute under physiological conditions and in the palmitic acid (PA)- induced in vitro model of NAFLD. STAT3 and cell cycle-related proteins (cyclin D1, c-myc and p21) were evaluated by Western blot. Under physiological conditions, LO2 cells and primary hepatocytes treated with various concentration of Lute for 12 and 24 h showed increased hepatocyte proliferation, especially with 20 µM treatment for 24 h. More notably, under the model conditions, co-incubation with 20 µM of Lute also markedly reversed PA-induced inhibition of cell proliferation and viability in primary hepatocytes. Mechanistically, Lute could activate STAT3 and subsequently increase cyclin D1 and cmyc expression, which positively regulates cell cycle progression, and decrease expression of p21, an inhibitor of cell cycle progression. Furthermore, Luteinduced hepatocyte proliferation-promoting efficacy was abolished by STAT3 inhibitor stattic. Collectively, Lute can alleviate PA-induced hepatocyte damage via activating STAT3-mediated hepatocyte regeneration.

[Effect of fragmented sleep on postoperative cognitive function and central neuroinflammation].

Objective: To investigate the effect of sleep fragmentation on perioperative neurocognitive disorders (PND) and central neuroinflammation by simulating sleep patterns of postoperative patients with sleep fragmentation in aged mice. Methods: Thirty-two elderly ICR mice were randomly divided into four groups (n=8): normal group (C), surgery group (S), fragmented sleep group (F), and surgery+fragmented sleep group (D). Fragmented sleep was conducted after internal fixation of tibia fractures, cognitive function was evaluated by novel object recognition (NOR) and fear conditioning (FC) test, and changes in expression of inflammatory cytokines in hippocampus were detected by ELISA. Results: NOR test: the recognition index (RI) of mice in group C, group S, group F and group D was 0.69±0.07, 0.48±0.07, 0.54±0.10 and 0.50±0.12, respectively. The RI of mice in group S, group F and group D was significantly lower than that in group C (t=4.885, 3.521 and 4.433, all P<0.01). There was no significant difference in RI between group S and group D (t=0.967 1, P>0.05). Contextual FC test: the freezing time of mice in group C, group S, group F and group D was(21.34±6.48), (13.83±4.26), (11.50±6.25) and (6.17±4.77) s, respectively. The freezing time of mice in group S, group F and group D was significantly lower than that in group C (t=2.722, 3.566, 5.496, P<0.05 or P<0.01). The freezing time of mice in group D was significantly lower than that in group S (t=2.774, P<0.05). Cue FC test: the freezing time of mice in group C, group S, group F and group D was (74.36±17.09), (43.91±9.71), (46.34±13.43) and (24.90±14.21) s, respectively. The freezing time of mice in group S, group F and group D was significantly lower than that in group C (t=4.393, 4.043 and 7.136, all P<0.01). The freezing time of mice in group D was significantly lower than that in group S (t=2.743, P<0.05). The levels of TNF-α, IL-6 and IL-1ß in hippocampus of mice in group S, F and D were significantly higher than those in group C, while the levels of TNF-α and IL-6 in hippocampus of mice in group D were significantly higher than those in group S, with statistically significant differences (P<0.05 or P<0.01). Conclusion: Postoperative fragmented sleep aggravates postoperative cognitive impairment and increases the hippocampal neuroinflammation in aged mice.

[The rotational stability of Toric intraocular lenses and influencing factors in cataract patients with different axial length].

Objective: To evaluate the rotational stability of the Toric intraocular lens (TIOL) and influencing factors in cataract patients with different axial length. Methods: This retrospective cohort study consecutively enrolled patients who had phacoemulsification and AcrySof TIOL implantation in Peking University Third Hospital from May 2018 to January 2019. Based on axial length, patients were divided into two groups. Group A consisted of patients whose axial length was ≤ 24 mm. Patients whose axial length was >24 mm were included in group B. Data at three months postoperatively were used to evaluate the rotational stability of TIOL and its correlation with axial length, corneal white to white distance, lens thickness and TIOL spherical power. And t test, nonparametric test, chi-square test and Spearman test were used for statistical analysis. Results: Group A enrolled 39 patients (17 males and 22 females), with a median age of 74 years (range, 36-86 years). Group B enrolled 26 patients (11 males and 15 females), with a median age of 68 years (range, 36-86 years). For the efficacy of TIOL, in group A, the best corrected distance visual acuity (BCDVA, logarithm of the minimum angle of resolution) was 0.30 (0.10, 1.00) preoperatively and 0.10 (0.00, 0.60) postoperatively, and the astigmatism was 2.11 (0.95, 5.10) D preoperatively and 1.00 (0.00, 1.75) D postoperatively. In group B, the BCDVA was 0.36 (0.05, 1.00) preoperatively and 0.05 (0.00, 0.40) postoperatively, and the astigmatism was 2.00 (0.78, 3.76) D preoperatively and 0.75 (0.00, 2.25) D postoperatively. Between group A and group B, there were no significant differences in BCDVA (P=0.604) and astigmatism (P=0.789) preoperatively.In these two groups, postoperative BCDVA and astigmatism both significantly improved compared to preoperative parameters (both P<0.01). Between group A and group B, there were no significant differences in BCDVA (P=0.536) and astigmatism (P=0.076) postoperatively. In terms of rotational stability, the rotation in group A was 5.15°±3.62°, and that in group B was 6.50°±4.66°. There was no statistical difference between two groups (P=0.195). As for predictability, the percentage of eyes with rotation ≤5° was 59.0% (23 eyes) in group A and 50.0% (13 eyes) in group B. There was no statistical difference between the two groups (P=0.647). There was no significant correlation between the rotational stability of TIOL and axial length, corneal white to white distance, lens thickness or TIOL spherical power (P=0.836, 0.568, 0.170, 0.365). Conclusions: The rotational stability of TIOL at three months postoperatively in patients whose axial length >24 mm is of no difference with patients whose axial length ≤ 24 mm. It has no correlation with axial length, corneal white to white distance, lens thickness and TIOL spherical power. (Chin J Ophthalmol, 2020, 56: 41-46).

Comparative Analysis of Visual System Disability Evaluation Criteria between China and the United States.

ABSTRACT: Gradation of Disability in Human Body Injuries （hereinafter referred to as Gradation） has been released and used since January 2017, and has become the most widely used standard in forensic science practice. This paper calculates and rates the visual system evaluation provisions of the current domestic disability evaluation criteria represented by the Gradation which used the methods of Guides to the Evaluation of Permanent Impairment （hereinafter referred to as GEPI） issued by American Medical Association （AMA）. Through comparing, a good correlation between the provisions in Gradation and whole person impairment rating index in GEPI was shown. On the basis of this, suggestions are put forward to amend some provisions of Gradation, in order to provide reference for the revision and further improvement of domestic standards and provisions.

Application of PRVEP Waveform Amplitude Ratio to Evaluate Visual Acuity and Its Forensic Significance.

ABSTRACT: Objective To research the correlation between the visual acuity ratio and pattern reversal visual evoked potential （PRVEP） P100 waveform amplitude ratio of both eyes. Methods Forty-seven volunteers were selected, and the visual chart visual acuity of both eyes was measured. The visual acuity ratio of the eye with poor vision to the eye with better vision was calculated by five grade notation method. The amplitudes of P100 waveforms of both eyes were recorded respectively by using black-and-white checkerboard PRVEP and chosing 1°, 15' stimulating visual angle, and the ratio of amplitudes between the two eyes was also calculated. SPSS 20.0 software was used to analyze the correlation between the visual acuity ratio and the ratio of P100 waveform amplitudes between the two eyes. Return test and linear regression analysis with the binocular ratio of P100 waveform amplitudes as the independent variable （x） and the binocular visual acuity ratio as the dependent variable （y） were made. Results There was a positive correlation between the binocular visual acuity ratio and the ratio of P100 waveform amplitudes under 15' stimulating visual angle （Pearson correlation coefficient was 0.62, P=0.000）. The fitting linear regression equation was y=0.090 x+0.846 （F=20.954, P=0.000）. There was no significant correlation between the binocular ratio of visual acuity and the binocular ratio of P100 waveform amplitudes under 1° stimulating visual angle （P>0.05）. Results of return test showed that there was no statistical significance in the difference between visual acuity estimated by equation and actual detected visual acuity. Conclusion In forensic appraisal of monocular injury, fitting linear regression equation of binocular visual acuity ratio and the binocular ratio of P100 waveform amplitudes under 15' stimulating visual angle, is helpful for visual acuity level estimation of the injured eye to some extent.

[Effects of remifentanil gradual withdrawal on remifentanil induced postoperative hyperalgesia].

Objective: To explore the effects of remifentanil gradual withdrawal on remifentanil induced postoperative hyperalgesia. Methods: Ninety patients from January to June 2018 undergoing elective laparoscopic hysterectomy under general anaesthesia at Ningbo NO.2 hospital, ASA Ⅰ or Ⅱ grade, aged 20-60, were enrolled in this study and randomly assigned to 3 groups (n=30): Group L (low dose remifentanil), Group H (high dose remifentanil) and Group G (high dose remifentanil with gradual withdrawal). Mechanical pain thresholds (MPT), visual analogue scale (VAS) and additional analgesics were recorded at 6 and 24 hours after the operation. Results: There was no significant difference among the VAS and additional analgesics in three groups at 6 and 24 hours after operation (P>0.05). There was no significant difference among the MPT in three groups before operation (P>0.05). The MPT of group L, group H and group G were (49.8±12.2), (35.5±13.0) and (48.6±11.4) g at 6 hours after surgery, and (51.4±14.3), (36.9±11.1) and (48.8±11.5) g at 24 hours after surgery, respectively, with statistically significant differences (F=12.6, 11.668, both P<0.01). The MPT of group H at 6 h and 24 h after surgery was lower than that of group L (all P<0.01), while the MPT of group G at 6 h and 24 h after surgery was significantly higher than that of group H (all P<0.01). No correlation was observed between MPT and VAS scores or additional analgesics at 6 and 24 hours postoperatively (P>0.05). Conclusion: Remifentanil gradual withdrawal significantly alleviated intraoperative administration of remifentanil induced postoperative hyperalgesia in laparoscopic hysterectomy patients.

[Comparative analysis of anatomic and non-anatomic hepatectomy for single small hepatocellular carcinoma with microvascular invasion].

Objective: To compare the efficacy and safety of anatomic hepatectomy and non-anatomic hepatectomy in the treatment of single small Hepatocellular carcinoma with MVI. Methods: The clinical data of 84 patients with single small Hepatocellular carcinoma with MVI in Beijing Chaoyang Hospital between January 2008 and December 2013 were retrospectively analyzed. Patients undergoing anatomical hepatectomy were enrolled in the AR group, and the patients undergoing non-anatomic hepatectomy were enrolled in the NR group. The efficacy and survival rate of the two groups were compared. Results: (1) Operation time, numbers of patients with volume of intraoperative blood loss ≥300 ml and number of patients with blood transfusion were (170±41)minutes, 8, 7 in the AR group and (148±35)minutes, 19, 18 in the NR group, respectively, with statistically significant differences between the 2 groups (P<0.05). (2) The 1-year, 2-year and 3-year overall survival rate were 85.7%, 68.6%, 57.1% in the AR group and 79.6%, 53.1%, 42.9% in the NR group, respectively. The 1-year, 2-year and 3-year progression-free survival rate were 80.0%, 62.9%, 51.4% in the AR group and 71.4%, 49.0%, 38.8%, in the NR group, respectively. There were statistically significant differences between the 2 groups both in the overall survival rate and the progression-free survival rate (P<0.05). (3) Prognostic factors analysis of HCC patients with MVI: result of univariate analysis showed that maximum diameter of tumor and surgical procedures were relative factors affecting overall survival and progression-free survival of HCC patients with MVI, AFP level was relative factors affecting progression-free survival of HCC patients with MVI, with statistically significant differences (P<0.05). Result of multivariate analysis showed that maximum diameter of tumor between 3.0 and 5.0 cm and non-anatomic liver resection were independent factors affecting poor overall survival and progression-free survival of HCC patients with MVI, and AFP≥20 µg/L and total bilirubin ≥20 µmol/L were independent factors affecting poor progression-free survival of HCC patients with MVI, with a statistically significant differences (P< 0.05). Conclusion: Anatomic hepatectomy for patients with single small hepatocellular carcinoma with microvascular invasion has better clinical efficacy and safety.

[Contrast Visual Evoked Potentials under Pattern Stimulus in Ocular Trauma].

OBJECTIVES: To study the characteristic of contrast visual evoked potentials （CVEP） in patients with ocular trauma. METHODS: Sixty patients defined as ocular trauma by forensic clinical examination in our center were selected, and split into 0.2-0.3 （Group A）, 0.3-0.5 （Group B） and ≥0.5 （Group C） according to the best corrected visual acuity. The variation characteristics of wave amplitude and latency of CVEP under 100%, 25% and 10% contrast were observed and analyzed statistically. RESULTS: （1） Under the same contrast, the wave amplitude of P100 decreased with the decrease of stimulus perspective. （2） Under the same stimulus perspective, the wave amplitude of P100 decreased with the decrease of contrast （P<0.05）. （3） Under the contrast of 100% and 25% with the same stimulus perspective （except 100% 7' perspective stimulus）, the difference between group A and group B had no statistical significance （P>0.05）. Between group A and group C, group B and group C, the wave amplitude of P100 gradually increased with the increase of vision （P<0.05）. Under the contrast of 10% with 15' stimulus perspective, the wave amplitude of P100 increased with the increase of vision （P<0.05）. （4） Under the same contrast with the same stimulation perspective, the latency of P100 wave shortened with the increase of vision, while the difference had no statistical significance （P>0.05）. Under the same stimulus perspective, the latency of P100 wave was prolonged with the decrease of contrast （P>0.05）. CONCLUSIONS: CVEP may become one of the possible methods for the evaluation of contrast visual acuity.

Construction of gene/protein interaction networks for primary myelofibrosis and KEGG pathway-enrichment analysis of molecular compounds.

The objective of this study was the development of a gene/protein interaction network for primary myelofibrosis based on gene expression, and the enrichment analysis of KEGG pathways underlying the molecular complexes in this network. To achieve this, genes involved in primary myelofibrosis were selected from the OMIM database. A gene/protein interaction network for primary myelofibrosis was obtained through Cytoscape with the literature mining performed using the Agilent Literature Search plugin. The molecular complexes in the network were detected by ClusterViz plugin and KEGG pathway enrichment of molecular complexes was performed using DAVID online. We found 75 genes associated with primary myelofibrosis in the OMIM database. The gene/protein interaction network of primary myelofibrosis contained 608 nodes, 2086 edges, and 4 molecular complexes with a correlation integral value greater than 4. Molecular complexes involved in KEGG pathways are related to cytokine regulation, immune function regulation, ECM-receptor interaction, focal adhesion, actin cytoskeleton regulation, cell adhesion molecules, and other biological behavior of tumors, which can provide a reliable direction for the treatment of primary myelofibrosis and the bioinformatic foundation for further understanding the molecular mechanisms of this disease.

Origin of shape resonance in second-harmonic generation from metallic nanohole arrays.

Second-harmonic generation (SHG) from periodic arrays of subwavelength rectangular air hole with various aspect ratios perforated in gold thin films can get resonantly enhanced for some specific geometric shapes. Here we clarify the physical origin of this shape resonance effect. A nonlinear coupled-mode theory is set up to solve energy conversion from fundamental wave (FW) mode to second-harmonic wave (SHW) mode within the nanoscale air hole. It reveals that several physical mechanisms, including the FW mode excitation amplitude, FW-SHW modal spatial overlap, FW-SHW mode phase mismatch, and SHW mode attenuation, are all geometric shape sensitive and altogether act to induce the SHG shape resonance effect. The theory agrees well with experimental observations and provides an accurate and complete explanation for the long-emphasized but elusive shape effect. The study may stimulate deeper insights to visualize general nonlinear nanophotonic processes and pave the way to engineering high-efficiency nonlinear nanophotonic devices.

Pharmacokinetics of febuxostat in healthy Chinese volunteers.

BACKGROUND: Febuxostat is a novel non-purine selective inhibitor of xanthine oxidase developed for the management of hyperuricemia in patients with gout. OBJECTIVE: To investigate the pharmacokinetics and also evaluate the effects of gender and food on the pharmacokinetics of febuxostat in healthy Chinese volunteers. METHODS: A phase I, 3-period study was performed in healthy Chinese male and female subjects. Subjects either received single 40 mg, multiple 40 mg and single 80 mg doses of febuxostat under fasted conditions, or received single 80 mg doses under fed condition. Plasma concentrations of febuxostat were collected and determined at 14 time points over 48 h. RESULTS: After 40 mg and 80 mg single dose administration of febuxostat, the C max were 2.308±0.812 and 4.559±1.246 µg/mL, the T max were 1.6±0.6 and 2.1±1.0 h, the t 1/2 were 6.8±1.7 and 6.7±1.9 h, and the AUC0-∞ were 7.704±1.723 and 16.34±3.87 µg∙h/mL, respectively. In the multiple-dose study at 40 mg dose for 6 consecutive days, the mean (SD) steady-state pharmacokinetic parameters on day 8 were similar to those following a single dose of febuxostat on day 1. In addition, food caused a decrease of 33% for C max and a delay of 0.3 h for T max. Gender had no significant effect on the pharmacokinetics of febuxostat. Febuxostat was well tolerated over the investigated dose range. CONCLUSION: Compared with the previous study, the pharmacokinetics of febuxostat appeared to be different between Chinese and other races.

Zoledronate inhibits phosphate and bone morphogenetic protein 2-induced extracellular calcification of vascular smooth muscle cells in vitro.

The aim of this study was to explore the effects of the bisphosphonate zoledronate on calcification induced by inorganic phosphate (Pi) and/or bone morphogenetic protein 2 (BMP-2) and the underlying mechanisms. Primary vascular smooth muscle cells (VSMCs) from rats were treated with 3 mM Pi or 3 mM Pi/BMP-2, with and without addition of zoledronate; 1.4 mM Pi served as a control. Calcium deposits, expression of core binding factor α-1 (Cbfa-1), osteopontin (OPN), parathyroid pituitary-specific transcription factor (Pit)-1 and Pit-2, and Pi uptake of VSMCs was determined. The calcification of VSMCs induced by elevated Pi or Pi/BMP-2 was significantly inhibited by zoledronate. The expression of Cbfa-1, OPN and Pit-1 was increased significantly after treatment with an elevated level of Pi or Pi/BMP-2, and this expression was significantly suppressed by addition of zoledronate. Pi uptake of VSMCs increased following treatment with elevated Pi and significantly decreased by addition of zoledronate. These results indicated that zoledronate effectively inhibited calcification induced by Pi/BMP-2, and this may have been achieved by means of the downregulation of expression of calcification-related proteins and uptake of Pi.

Arbuscular mycorrhizal fungi associated with the Meliaceae on Hainan island, China.

Species richness, spore density, frequency of occurrence, and relative abundance of AM fungi were determined in rhizosphere soil samples from nine tropical rainforest sites on Hainan island, south China, and the arbuscular mycorrhizal (AM) status of members of the Meliaceae was examined. All 28 plant taxa investigated (25 species including two varieties of 1 species and three varieties of another) were colonized by AM fungi. The mean proportion of root length colonized was 56% (range 10-95%). Vesicles were observed in 27 and hyphal coils in 26 of the 28 plant taxa. Mycorrhizas were of the Paris-type or intermediate-type, with no Arum-type mycorrhizas observed. Species richness of AM fungi varied from 3 to 15 and spore density from 46 to 1,499 per 100 g rhizosphere soil. Of 33 AM fungal taxa in five genera isolated and identified, 18 belonged to Glomus, 9 to Acaulospora, 1 to Entrophospora, 2 to Gigaspora, and 3 to Scutellospora. Acaulospora and Glomus were the dominant genera identified. Glomus claroideum was the taxon most commonly isolated, with a frequency of occurrence of 56.5% and relative abundance of 10.4%. A positive correlation was found between percentage of root length colonization and species richness. However, there was no correlation between spore density and percentage of root length colonized by AM fungi.

Neurotrophin-3 modulates noradrenergic neuron function and opiate withdrawal.

Somatic symptoms and aversion of opiate withdrawal, regulated by noradrenergic signaling, were attenuated in mice with a CNS-wide conditional ablation of neurotrophin-3. This occurred in conjunction with altered cAMP-mediated excitation and reduced upregulation of tyrosine hydroxylase in A6 (locus coeruleus) without loss of neurons. Transgene-derived NT-3 expressed by noradrenergic neurons of conditional mutants restored opiate withdrawal symptoms. Endogenous NT-3 expression, strikingly absent in noradrenergic neurons of postnatal and adult brain, is present in afferent sources of the dorsal medulla and is upregulated after chronic morphine exposure in noradrenergic projection areas of the ventral forebrain. NT-3 expressed by non-catecholaminergic neurons may modulate opiate withdrawal and noradrenergic signalling.

Interrelations of opioids with monoamines in descending inhibition of nociceptive transmission at the spinal level: an immunocytochemical study.

This study was designed to reexamine a previous proposal of whether the opioid-like substances (OLS) being acting mainly as an intrinsic spinal mediator in the descending inhibition of nociception of the bulbospinally projecting NE-ergic, and/or 5-HT-ergic terminals in the dorsal horn by using an immunocytochemical method. The effects of intrathecal (i.t.) phentolamine (Ph), cyproheptadine (Cyp), and naloxone (Nal), administered separately or coadministered by two of them, on the expression of Fos-like-immunoreactive (FLI) neurons were observed on both sides of the lumbar dorsal horn of rats, in which equal volumes of formalin were injected into two hindpaws and the ipsilateral dorsolateral funiculus (DLF) was transected at the thoracic level antecedently. The results showed: (1) when rats were pretreated with i.t. saline, the number of nociceptive FLI neurons was significantly lowered 44% (p<0.01) on the side of the lumbar dorsal horn with intact DLF compared to the opposite side with sectioned DLF; (2) when rats were separately pretreated with i.t. Ph, Cyp and Nal, the reduction of FLI neurons on the DLF-intact side were decreased by 27% (p<0.01), 21% (p<0.01), and 25% (p<0.01), respectively; (3) when rats were pretreated with combined i.t. Ph+Cyp, the reduction on the intact side was eliminated almost completely (4%); (4) when rats were pretreated with combined i.t. Ph+Nal, the reduction on the intact side was 21% (p<0.01); and (5) when rats were pretreated with i.t. Cyp+Nal, the reduction on the intact side was 9.1%. These results suggest that: (1) nearly all the suppressive action exerted by the DLF-descending fibers are produced by the release of either NE or 5-HT as neurotransmitters at the spinal level; (2) most of the opioid-like substances act as an intrinsic spinal mediator mainly for the descending NE-ergic, but in a lesser extent for the 5-HT-ergic terminals in the dorsal horn circuitry; and (3) some OLS-ergic interneurons may only be activated by local nociceptive input.

Nociceptive c-fos expression in supraspinal areas in avoidance of descending suppression at the spinal relay station.

The number and distribution of Fos-like-immunoreactive neurons in different supraspinal brain areas induced by formalin injection into one hindpaw was estimated in rats with transected dorsal half of the spinal cord at the thoracic level in an attempt to avoid most of the descending modulatory actions. The results showed that: (i) after spinal lesion, the peripheral noxious inputs, going up mainly through the ventral spinal cord, elicited a more widespread and densely located Fos-like-immunoreactive neurons in subcortical areas, many of them showed no Fos expression when noxious stimulation was given in rats with intact spinal cord; (ii) at the same time, a small number of subcortical areas, such as the lateral ventroposterior thalamic nucleus and dorsal raphe nucleus, exhibited no significant increase of nociceptive Fos-like immunoreactive neurons after spinal lesion as compared to that with intact spinal cord; and (iii) there appeared a prominent expansion of cortical areas with densely located Fos-like-immunoreactive neurons in spinal-lesioned rats as compared with the limited labelled areas in the control group with intact spinal cord. These results indicate that: (i) in avoiding the spinally descending modulatory mechanisms, more widespread supraspinal and cortical neurons will be recruited and activated in response to the noxious stimulation; and (ii) the descending systems exert differential actions on the spinal targets which project nociceptive signals to different supraspinal regions. The implication of these facts is discussed.

Effects of intrathecal monoamine antagonists on the nociceptive c-Fos expression in a lesioned rat spinal cord.

Effects of intrathecal (i.t.) administration of monoamine antagonists on formalin-induced neuronal c-Fos expression in two sides of the lumbar dorsal horn were observed in rats with unilateral transection of the dorsolateral funiculus at T11-12 level. The results showed that: 1) pretreated with i.t. normal saline (control) and then an equal volume of formalin was injected into the two hindpaws, the number of Fos-like immunoreactive neurons were 44% lower on the side of lumbar dorsal horn with intact dorsolateral funiculus (57 +/- 3.1 vs. 103 +/- 3.8). 2) Pretreatment with i.t. phentolamine (a non-selective alpha-adrenoceptor antagonist) caused an increase of Fos-like immunoreactive neurons on the intact side so showing only a reduction rate of 23% to the lesioned side (p < .01); 3) pretreatment with i.t. cyproheptadine (a 5-HT-receptor antagonist) caused a similar reduction rate of 21% (p < .01) of Fos-like immunoreactive neurons on the intact side; and 4) combined i.t. pretreatment with phentolamine and cyproheptadine caused a reduction of Fos-like immunoreactive neurons of only 4% on the intact side, namely, the differences in the number of Fos-like immunoreactive neurons on two sides of the lumbar spinal cord owing to the unilateral dorsolateral funiculus lesion were nearly abolished by i.t. coinjection of phentolamine and cyproheptadine. The results indicate that 1) peripheral noxious inputs can provoke a spinally-descending inhibitory effect on the spinal nociceptive transmission via the dorsolateral funiculus and 2) the descending fibers in dorsolateral funiculus exert their action mainly through the release of either norepinephrine or 5-HT at the spinal level.

Peripheral NMDA receptors contribute to activation of nociceptors: a c-fos expression study in rats.

By using immunocytochemical techniques, we demonstrated that: (1) unilateral injection of N-methyl-D-aspartate (NMDA; 10, 20, 50 micromol) into the plantar aspect of hindpaw of the normal waked rats elicited a dose-dependent increase of c-fos expression in the superficial laminae on the side of the spinal dorsal horn ipsilateral to the injection; (2) combined injection of MK-801, a non-competitive NMDA receptor antagonist, with formalin into the hindpaw could suppress formalin-induced c-fos expression in the dorsal horn, with a stronger suppression after higher doses of MK-801 being injected. These results strongly suggest that NMDA receptors might be located in the membrane of peripheral axonal terminals of the dorsal root ganglion neurons and might be involved in the activation of nociceptors.