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Objective To evaluate the role of phosphatidylinositol 3-kinase (PI3K) p110β in spinal dorsal horn neurons in the development of arthritic pain (AP) in rats and the relationship with transient receptor potential vanilloid 1 (TRPV1) and acid-sensing ion channel (ASIC)1 a.Methods Forty adult female Sprague-Dawley rats in which intrathecal catheters were successfully placed,aged 3 months,weighing 250-300 g,were randomly divided into 4 groups (n =10 each):control group (group C),group AP,AP + PI3K p110β missense oligo-deoxynucleotide group (group MS) and AP + PI3K p110β antisense oligo-deoxynucleotide group (group AS).AP was induced by injecting complete Freund's adjuvant into the ankle joint cavity of right hindpaw.Normal saline 20 μl,missense oligo-deoxynucleotide 15 μg (20μl) and antisense oligo-deoxynucleotide 15 μg (20 μl) were administered intrathecally once a day for 6 consecutive days starting from the time immediately after arthritis was induced in groups AP,MS and AS,respectively.Mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured 1 day before operation (T0) and on days 4,7,10 after operation (T1-3).The rats were then sacrificed after the last measurement of pain threshold at T3.L4-6 segment of the spinal cord was removed for detection of expression of PI3K p110β (by Western blot),and TRPV1 and ASICla (by immunohistochemistry)in spinal dorsal horn neurons.Results Compared with group C,MWT and TWL were significantly decreased atT1-3,and the expression of PI3K p110β,TRPV1 and ASIC1a was up-regulated in the other 3 groups(P＜ 0.01).MWT and TWL were significantly higher at T1-3,and the expression of PI3K p110β,TRPV1 and ASIC1a was lower in group AS than in groups AP and MS (P ＜ 0.01).Conclusion PI3K p110β in spinal dorsal horn neurons is involved in the development of AP in rats,and the mechanism is related to up-regulation of TRPV1 and ASIC1a expression in spinal dorsal horn neurons.
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Despite its clinical importance, the underlying central mechanisms of pruritic behaviors are poorly understood. To investigate the role of nociceptive arcuate nucleus neurons in chloroquine-induced pruritic behaviors in mice, we tested the effect of arcuate nucleus neurons and interscapular brown adipose tissue (IBAT) on itch produced by intradermal injection of chloroquine in the nape of the neck. Our results provide several lines of evidence for an important role of nociceptive arcuate nucleus neurons in chloroquine-induced pruritic behavior: (1) Intradermal microinjection of chloroquine resulted in a dramatic increase in itch behaviors accompanied by the activation of c-Fos positive neurons in arcuate nucleus; (2) Microinjection of chloroquine significantly increased IBAT temperature in the mice. These findings suggested that chloroquine-induced pruritic behaviors were associated with the activity of nociceptive arcuate nucleus neurons.
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Despite its clinical importance, the underlying central mechanisms of pruritic behaviors are poorly understood. To investigate the role of nociceptive arcuate nucleus neurons in chloroquine-induced pruritic behaviors in mice, we tested the effect of arcuate nucleus neurons and interscapular brown adipose tissue (IBAT) on itch produced by intradermal injection of chloroquine in the nape of the neck. Our results provide several lines of evidence for an important role of nociceptive arcuate nucleus neurons in chloroquine-induced pruritic behavior: (1) Intradermal microinjection of chloroquine resulted in a dramatic increase in itch behaviors accompanied by the activation of c-Fos positive neurons in arcuate nucleus; (2) Microinjection of chloroquine significantly increased IBAT temperature in the mice. These findings suggested that chloroquine-induced pruritic behaviors were associated with the activity of nociceptive arcuate nucleus neurons.
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Animals , Male , Mice , Arcuate Nucleus of Hypothalamus , Chloroquine , Mice, Inbred C57BL , Nociceptors , Physiology , PruritusABSTRACT
Neurons in the laterodorsal tegmentum (LDTg) and pedunculopontine tegmental nucleus (PPTg) play important roles in central autonomic circuits of the kidney. In this study, we used a combination of retrograde tracers pseudorabies virus (PRV)-614 and fluorescence immunohistochemistry to characterize the neuroanatomic substrate of PPTg and LDTg innervating the kidney in the mouse. PRV-614-infected neurons were retrogradely labeled in the rostral and middle parts of LDTg, and the middle and caudal parts of PPTg after tracer injection in the kidney. PRV-614/TPH double-labeled neurons were mainly localized in the rostral of LDTg, whereas PRV-614/TH neurons were scattered within the three parts of LDTg. PRV-614/TPH and PRV-614/TH neurons were located predominantly in the caudal of PPTg (cPPTg). These data provided direct neuroanatomical foundation for the identification of serotonergic and catecholaminergic projections from the mid-brain tegmentum to the kidney.
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Objective To investigate the distribution and severity of cerebral artery stenosis and the prognosis in elderly patients with acute cerebral infarction using digital subtraction angiography (DSA). Methods The 432 elderly patients with acute cerebral ischemia infarction underwent DSA,and they were divided into two groups: elderly group (n= 320) and non-elderly group (n= 112). The characteristics of distribution and severity of cerebral artery stenosis, the relationship between artery stenosis and relative risk factors, and the prognosis of acute cerebral infarction were analyzed.Results In elderly group, 270 cases (84.3%) had intra- and extra- cranial artery stenosis, of which 98 patients (30.6%) with pure extracranial arterial stenosis, 132 patients (41.3%) with combined extra- and intra-cranial artery stenosis. They were both significantly higher than the corresponding data in non-elderly group [23 cases (20.5%) and 28 cases (25%), P＜0.05 and 0.01]. The prevalences of moderate and severe cerebral artery stenosises were higher in elderly group than in nonelderly group [224 locations (52.1%) vs. 51 locations (40.8%), P＜0. 05]. The number of patients with previous history of cerebrovascular disease was much more and the prognosis was much worse in elderly group than in non-elderly group (both P＜0.05), Conclusions The elderly patients with cerebral infarction have severer cerebral artery stenosis, increased proportion of multivessel disease and poor prognosis. So it is very important to take aggressive treatment as soon as possible, and to make secondary prevention and effective rehabilitation so as to improve their prognosis.
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The effect of morphine and naloxone on release of the excitatory amino acids (EAAs) of spinal astrocytes induced by TNF-α was studied. Astrocytes were purified from 2- to 3-day old SD rats and divided into 8 groups: group 1 (without any stimulatants); group 2 (10 ng/ml TNF-α);group3 (10 ng/ml TNF-α+0.5 μmol/L morphine); group 4 (10 ng/ml TNF-α+1. 0 μmol/L morphine); group 5 (10 ng/ml TNF-α+ 2. 0 μmol/L morphine) ; group 6 (10 ng/ml TNF-α+ 0. 5 μmol/L naloxone); group 7 (10 ng/ml TNF-α+ 1.0 μmol/L naloxone) ; group 8 (10 ng/ml TNF-α+2.0 μmol/L naloxone). In group 2, 3, 4 and 5, 0, 0.5, 1.0 or 2.0 μmol/Lmorphine was added to the cells cultured with serum-free Neurobasal/B27 medium containing 10 ng/ml TNF-α respec-tively, while in group 6, 7 and 8, 0.5, 1.0 or 2.0 μmol/Lnaloxone was added respectively to the cells cultured with serum-free Neurobasal/B27 medium containing 10 ng/ml TNF-α. After 30 min incubation, high-pressure liquid chromatography (HPLC) was used to measure the levels of EAAs in all cultured cells. The results showed the level of EAAs in group 2 was significant higher than in group 1 (P＜0.01). As compared with group 2, the levels of EAAs in group 3, 4 and 5 were decreased with the difference being significant between group 5 and group 2 (P＜0.01) or between group 4 and group 2 (P＜0.05). The levels of EAAs in group 6, 7 and group 8 was significantly lower than in group 2 (P＜0.05 or P＜0.01). It was concluded that TNF-α could promote the release of glutamate and aspartate from astrocytes, and morphine and naloxone might reduce the release of EAAs in cultured spinal astrocytes induced by TNF-α.
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Objective To investigate the effects of propofol the expression of inducible nitric oxide synthase (iNOS) in the spinal cord in rats with chronic neuropathic pain. Methods Forty adult Wistar rats of both sexes weighing 200-220 g were used in this study. Chronic neuropathic pain was produced by loose ligatures placed on the left sciatic nerve. Propofol or normal saline (NS) was given intraperitoneally (i.p. ) once a day for 6 days, seven days after sciatic nerve ligation. The animals were randomly divided into 4 groups (n = 10) : group Ⅰreceived NS 50 ml?kg-1 i.p. but no sciatic nerve ligation; group Ⅱ received sciatic nerve ligation and NS 50 ml?kg-1 i.p. ; group Ⅲ and Ⅳ received sciatic nerve ligation and propofol 50ml?kg-1 (Ⅲ) or75ml?kg-1 (Ⅳ) i.p. . Withdrawal threshold of both hind paws to Von Frey filaments was measured on the 6th , 10th and 12th days after sciatic nerve ligation. The animals were then sacrificed and the lumbar segment (L4-5) of the spinal cord was removed for the detection of iNOS mRNA expression by RT-PCR technique on the 12th day. Results The withdrawal threshold to Von Frey filament of both hind paws was significantly higher on the 10th and 12th days in the two propofol groups (group Ⅲ and Ⅳ) than in group Ⅱ(P
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Objective Glutarnic acid, an important excitatory neurotransmitter, plays an important role in morphine dependence and tolerance. Astrocyte (AST) takes up giutamic acid which is transformed into glutamine, the precursor of GABA, by means of intracellular glutaminase. The aim of thin study was to investigate the effect of ketamine on glutamate release in cultured spinal ASTs chronically treated with morphine. Methods ASTs were isolated from 1-3 day old SD rats and divided into 8 groups : control group and group A, B1, B2, B3 , C1, C2, C3. The isolated ASTs were cultured and incubated for 48h in the presence (group A, B1-3, C1-3) and absence (control group) of 10?mol?L-1 morphine.Then the ASTs were transferred to liquid culture medium Neurobasal / B27 containing no serum. No drug was added in group A. Morphine 0.1 ,1 or 10?mol?L-1 was added in group B1-3 and ketamine 0.4, 4 or 40?mol?L-1 in group C1-3. After being incubated for 15 min, naloxone 10?mol?L-1 was added in group B1-3 and C1-3. After another 30 min incubation the gluamate concentration in supernatant was measured using HPLC. Results There was no significant difference in glutamate concentration between control group and group A ( P
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Objective To investigate the effect of ketamine, the NMDA receptor antagonist, on inducible nitric oxide gynthase (iNOS) mRNA expression in the spinal cord during the development of morphine tolerance. Methods Thirty Kunming mice weighing 18-22 g were randomly divided into 5 groups ( n = 6 each): A control group received normal saline (NS) only; B chronic morphine tolerance group received subcutaneous morphine 10 mg?kg-1 followed by IP NS after an interval of 30 min, twice a day for 9 days and C, D, E ketamine groups received subcutaneous morphine 10 mg?kg-1 followed by IP ketamine 5 (group C) or 10 (group D) or 20 (group E) mg?kg-1 after an interval of 30 min, twice a day for 9 days. One hour after the last drug administration the animals were decapitated and the lumbar enlargement of the spinal cord was isolated and the iNOS mRNA expression in the spinal cord was detected by RT-PCR. Results Expression of iNOS mRNA was not detectable in group A but increased dramatically in group B. The iNOS mRNA expression was significantly lower in group D and E (ketamine 10 and 20 mg?kg-1 IP) than in group B and C (ketamine 5 mg?kg-1) . Conclusion Ketamine antagonizes the development of chronic morphine tolerance in mice through down-regulation of iNOS mRNA expression in the spinal cord.
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Objective Recent studies have shown that activation of spinal astrocytes (ASTs) may be involved in the development of morphine tolerance. The purpose of this study was to investigate the effect of ketamine (K) on spinal ASTs in mice tolerant to morphine (M) .Methods Thirty Kun-Ming mice of both sexes weighing 18-22 g were randomly divided into 5 groups of six animals each : (A) control group received only subcutaneous (s.c.) and intraperitoneal (i.p.) normal saline (NS); (B) chronic M-tolerance group received M 10 mg?kg-1 s.c. followed after 30 min by NS 10 ml?kg-1 i.p. twice a day (at 8:00 and 17:00) for 9 days;(C), (D), (E) K group received M 10 mg?kg-1 s.c. followed after 30 min by K 5 mg? kg-1(C), 10 mg?kg-1 (D) or 20 mg?kg-1 (E) i.p. twice a day for 9 days. Pain threshold was estimated by measuring paw withdrawal response to Von Frey filament stimulation every other day (1st, 3rd, 5th, 7th, 9th) In after second administration of drugs. The percentage of maximal possible effect (MPE% ) was calculated : MPE% = [ (test group PWTV - control group PWTV) / (15 - control group PWTV)] ? 100% (PWTV = paw withdrawal threshold value). On the 9th day after pain threshold was measured the animals were sacrificed and lumbosacral segment of spinal cord was removed. The changes in spinal ASTs were detected by immunohistochemistry. The average areas of GFAP immuno-reactive cells in the dorsal horn were measured to show the degree of spinal AST activation. Results 1. MPE% was 0 at all time points in group A. In group B MPE% was 42.8% on the 1st and 3rd day and gradually decreasing on the 5th and 7th day and became 0 on the 9th day signifying full development of morphine tolerance. In group C the change in MPE% was almost the same as in group B. In group D and E MPE % tended to decrease but was still above 30% at all time points signifying that ketamine 10 and 20 mg?kg-1 could partly antagonize the development of morphine tolerance. 2. In group B the staining of GFAP immuno-reactive cells was heavier and the average areas were significantly larger than in group A (P