ANP-mediated cGMP signaling and phosphodiesterase inhibition in the rat cervical spinal cord

Natriuretic peptides (NP) and the corresponding receptors are present in the rodent spinal cord. We have studied the structures which respond to atrial natriuretic peptide, brain natriuretic peptide, or C-type natriuretic peptide with an increased synthesis of cGMP. NP-responsive cGMP-producing structures were observed in laminae I–III, and X, and in addition in ependymal cells, astrocytes and a subpopulation of dorsal root ganglion cells. As the cGMP concentration is controlled by the rate of synthesis and the rate of breakdown by phosphodiesterases, we studied NP-responsive structures in spinal cord slices incubated in the presence of different phosphodiesterase inhibitors. We studied EHNA and BAY 60-7550 as selective PDE2 inhibitors, sildenafil as a selective PDE5 inhibitors, dipyridamole as a mixed type PDE5 and PDE10 inhibitor, rolipram as a PDE4 inhibitor, and SCH 81566 as a selective PDE9 inhibitor. Double immunostainings showed that cGMP-IR colocalized partial with the vesicular acetylcholine transporter molecule in lamina X, with Substance P in a subpopulation of neuronal fibers situated dorsolateral, and with a subpopulation of CGRP-IR dorsal root ganglion neurons. Colocalization of cGMP-IR was absent with parvalbumin, synaptophysin, and the vesicular transporter molecules for GABA and glutamate.

It is concluded that NPs in the spinal cord are probably involved in integrating intersegmental sensory processing in the spinal cord although the greater part of the NP-responsive cGMP-producing fibers could not be characterized. PDE2, 5, and 9 are involved in regulating NP-stimulated cGMP levels in the spinal cord. NPs may have a role in regulating cerebrospinal fluid homeostasis.     

Regional specific effects of nitric oxide donors and cGMP on the electrical activity of neurons in the rat spinal cord

Numerous functional studies establish the role of nitric oxide (NO) as a neuromodulator in the central nervous system which affects synaptic transmission. However, there are only a few reports indicating a direct and postsynaptic effect of nitric oxide on the electrical activity of neurons in the central nervous system. The aim of this study was to characterize the effect of nitric oxide on spontaneously active neurons in spinal cord slices using an extracellular recording technique. Because in the lumbar rat spinal cord the NO producing enzyme NO-synthase is primarily located in the superficial dorsal horn (laminae I+II) and around the central canal (lamina X), we restricted our recordings to these areas. While the majority of neurons increased their electrical activity during superfusion with the NO-donor sodium nitroprusside (SNP) in lamina X, neurons in laminae I+II were mainly inhibited by SNP. The excitatory and the inhibitory effects were dose-dependent and reversible and were mimicked by other NO-donors and membrane permeable cyclic guanosine monophosphate (8Br-cGMP) on the same neurons. The spinal cord slice preparation contains functional NO-synthase (NOS), because selective blockade of NOS increased the spontaneous activity of those neurons from laminae I+II which were inhibited by SNP and this effect could be reversed by superfusion with the natural substrate for NOS, -arginine. It is concluded that NO can activate and inhibit the activity of spinal cord neurons by raising cGMP levels and that these effects are lamina specific. A general consequence of our results is that the NO-induced production of cGMP alone does not allow any prediction about an excitatory or inhibitory effect of NO on the discharge rate of neurons. Thus the NO mediated increase and decrease in neuronal activity is probably the result of intracellular mechanisms downstream from the production of cGMP which results in the activation or inhibition of different ion channels on neurons in laminae I+II and X.     

Postnatal development of nitric oxide synthase type 1 expression in the lumbar spinal cord of the rat: a comparison with the induction of c-fos in response to peripheral application of mustard oil

The distribution of the neuronal isoform of the enzyme nitric oxide synthase (type 1) has been investigated in the lumbar spinal cords of neonatal rats (2–20 days old). Large multipolar neurones were present from day 2 around the central canal, in a band across the neck of the dorsal horn and at the thoracic level in the intermediolateral cell column, whereas staining was absent from laminae II. By 20 days the laminae II staining was similar to that found in the adult. NOS expression in lamina II paralleled the development of c-fos expression in this lamina in response to peripheral application of mustard oil.     

SPANTIDE抑制大鼠甲醛试验中脊髓中央管周围区域NOS表达的上调礼物(英文)

目的:本实验观察非选择性NK受体拮抗剂[D-ARG1,D-TRP7.9,LEU11]-SUBSTANCE P(SPANTIDE)对大鼠甲醛实验诱导的脊髓中央管周围灰质区域NOS表达的影响。方法:右后掌足底皮下注射甲醛(5％,0．2 ML)诱导持续性痛及痛过敏,用缩足反射实验测定大鼠痛反应。应用NADPH-D组织化学法观察NOS的表达。SPANTIDE于甲醛注射前5 MIN经L5-L6腰椎间隙鞘内注射。结果:(1)足底注射甲醛引起大鼠疼痛行为反应,包括抓、咬、舔、注射侧后爪抬离盒底等。伴随着这些行为反应,脊髓L5节段中央管周围灰质区(第X板层)NOS表达上调。(2)预先给予 SPANTIDE能抑制大鼠甲醛试验第二时相注射侧肢体的自发性退缩反射,同时抑制了脊髓中央管周围灰质区NOS表达的上调。结论:SP在大鼠甲醛试验中脊髓中央管周围区域NOS表达上调中起着重要的作用。     

诱导型一氧化氮合酶在强啡肽致脊髓损伤中的作用

目的：探讨诱导型一氧化氮合酶（ｉＮＯＳ）在强啡肽致脊髓损伤中的作用。方法：［３Ｈ］－左旋精氨酸转化法测定腹侧和背侧脊髓ｉＮＯＳ活性,原位杂交法观测脊髓ｉＮＯＳｍＲＮＡ表达及其细胞分布。结果：大鼠蛛网膜下腔注射（ＩｎＩ）强啡肽Ａ１－１７（Ｄｙｎ）２０ｎｍｏｌ引起持久性截瘫和迟发性神经元死亡;在Ｄｙｎ致瘫后２～３ｈｉＮＯＳｍＲＮＡ表达开始增多增强,４ｈ达高峰,２４ｈ和４８ｈ仍见广泛表达,其分布以胶质细胞和大运动神经元为主;腹侧脊髓ｉＮＯＳ活性在Ｄｙｎ致瘫后４ｈ显著升高,并持续至２４ｈ和４８ｈ;提前１０ｍｉｎＩｎＩ选择性ｉＮＯＳ抑制剂氨基胍１μｍｏｌ可显著对抗Ｄｙｎ２０ｎｍｏｌ引起的持久瘫及伤后４ｈ腹侧脊髓ｉＮＯＳ活性升高。结论：ｉＮＯＳ持续性高表达与Ｄｙｎ致脊髓损伤机制有关     

Serotonin receptors 5-HT<Subscript>1A</Subscript> and 5-HT<Subscript>3</Subscript> reduce hyperexcitability of dorsal horn neurons after chronic spinal cord hemisection injury in rat

Spinal cord injury (SCI) results in abnormal pain syndromes in humans. In a rodent model of SCI, T13 spinal hemisection results in allodynia and hyperalgesia due in part to interruption of descending pathways, including serotonergic (5-HT) systems, that leads to hyperexcitability of dorsal horn neurons. To characterize further the role of 5-HT and 5-HT receptor subtypes 5-HT_1A and 5-HT₃ in neuronal activation after hemisection, we have examined the responsiveness of dorsal horn neurons to a variety of innocuous and noxious peripheral stimuli. Male Sprague-Dawley rats, 150–175 g, were spinally hemisected (n=40) at T13 and allowed 4 weeks for development of mechanical allodynia and thermal hyperalgesia. Animals then underwent electrophysiologic recording and the results were compared with those from sham controls (n=15). Evoked responses of convergent dorsal horn neurons (n=224 total) at L3–L5 to innocuous and noxious peripheral stimuli were characterized after administration of vehicle, 5-HT (25, 50, 100, and 200 μg), 5-HT (100 μg) in conjunction with the selective 5-HT_1A antagonist WAY 100135 (100 μg), the 5-HT₃ antagonist MDL 72222 (100 μg), the selective 5-HT_1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 150 μg), or the 5-HT₃ agonist 2-Me-5HT (75 μg), with or without pretreatment with antagonists; all treatments were delivered topically onto the cord adjacent to the recording electrode. In hemisected animals, increased responsiveness of convergent cells to all peripheral stimuli was observed bilaterally when compared to controls. No changes in ongoing background activity were present. In control animals, only the highest dose of 5-HT (200 μg) was sufficient to reduce evoked activity, whereas in hemisected animals a concentration-dependant decrease in response was observed. In hemisected animals, both 5-HT_1A and 5-HT₃ receptor antagonism reduced the effectiveness of 5-HT, restoring elevated evoked activity by up to 70% at the doses tested. Administration of 5-HT_1A and 5-HT₃ receptor agonists also decreased hyperexcitability, effects prevented by pretreatment with corresponding antagonists. These results demonstrate the development of denervation supersensitivity to 5-HT following SCI, corroborate behavioral studies showing the effectiveness of 5-HT in reducing allodynia and hyperalgesia after SCI, and contribute to a mechanistic understanding of the role of 5-HT receptor subtypes in chronic central pain. Electronic Publication     

Depression by nicotine of pain-related nociceptive activity in the rat thalamus and spinal cord

Summary To assess the possible role of nicotinergic control in nociception and pain, experiments were carried out on rats under urethane anesthesia in which nociceptive activity was elicited by electrical stimulation of afferent C fibers in the sural nerve and recorded from single neurones in the thalamus and from ascending axons in the spinal cord. Intravenous administration of nicotine (0.01–0.5 mg/kg) depressed the nociceptive activity evoked in the thalamus and the spinal cord in a dose-dependent way. The maximum depression in thalamus and spinal cord was 40% of control activity and obtained at a dose of 0.025 mg/kg. Likewise, local administration of nicotine to the spinal cord by intrathecal injection (5, 10, and 30 g) reduced the nociceptive activity evoked in neurones of the thalamus and in ascending axons of the spinal cord, the maximum of the depression being 40% of control activity. The depressant effect of nicotine (0.05 mg/kg) was reduced by mecamylamine (1 mg/kg) but not by atropine (0.5 mg/kg). It is concluded that the antinociceptive effect of nicotine is due to a specific action of the alcaloid at the spinal level.     

Induction of spinal cord neuronal nitric oxide synthase (NOS) after formalin injection in the rat hind paw

The nitric oxide synthase (NOS) inhibitor t,-nitroarginine methyl ester has been found to exhibit antinociceptive activity in a rat model of pain [Kitto, K.F. et al., Neurosci. Lett., 148 (1992) 1–5; Lee, J.H. et al., NeuroReport, 3 (]992) 841–844; Moore, P.K. et al., Br. J. Pharmacol., 102 (1991) 198–202]. We investigated the hypothesis that hind paw injection of formalin increases the number of dorsal horn neuronal nitric oxide synthase (nNOS) containing neurons. Results showed a bilateral increase in the number of nNOS-positive neurons at the L4–5 dorsal horn area following formalin injection. The increase was always greater on the ipsilateral side compared to the contralateral side. This upregulation of nNOS following formalin stimulation of the hind paw suggested that nitric oxide (NO) may play a role in the central mechanism of hyperalgesia that follows peripheral inflammation.     

iNOS expression in rat aorta is increased after spinal cord transection: a possible cause of orthostatic hypotension in man

Orthostatic hypotension commonly occurs in persons with spinal cord injury (SCI), limiting rehabilitation and independence. Findings of increased production of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) after exposure to simulated microgravity suggest that increased iNOS expression contributes to OH in persons with SCI. To test this possibility, male Wistar rats underwent surgical transection of the spinal cord (T10) or sham-SCI surgery followed by euthanasia 3, 7 or 14 days later. Expression in thoracic aortic of inducible (iNOS), endothelial (eNOS) and neuronal (nNOS) NOS was then determined. In SCI rats, expression of iNOS mRNA was decreased at 3 days, had returned to normal levels of expression at 7 days and was increased at 14 days post-SCI (1.8-fold). In contrast, levels of eNOS mRNA were increased at 3 days (1.4-fold), then declined over time reaching levels by day 14 that were reduced compared to sham-SCI (0.23-fold). There were no significant effects of SCI on nNOS expression. These findings suggest a possible role for increased iNOS expression in the pathogenesis of OH in persons with SCI.     

Nociceptive neurones in the superficial dorsal horn of cat lumbar spinal cord and their primary afferent inputs

Summary The morphology, background activity and responses to stimulation of primary afferent inputs of small neurones in the superficial dorsal horn which could only be excited from the skin by noxious stimulation were investigated by intracellular recording and ionophoresis of HRP. Neurones which gave similar responses to afferent stimulation were morphologically heterogeneous with respect to dendritic tree geometry and axonal projection, but were located around the lamina I/II border. Cutaneous excitatory receptive fields responding to noxious stimulation were generally small; most neurones had more extensive inhibitory fields responding to innocuous mechanical stimulation, in many cases overlapping the excitatory fields. Generally, stimulation of the excitatory field resulted in depolarization of the neurone and increased action potential firing, and stimulation of the inhibitory field resulted in hyperpolarization. Electrical stimulation of peripheral nerves revealed the existence of converging excitatory inputs carried by different fibre groups, and all neurones received an inhibitory input activated at low threshold. Excitatory responses were short-lived and occurred consistently in response to repeated stimulation. Central delay measurements gave evidence of a number of A monosynaptic inputs but only one A monosynaptic input; inhibitory inputs along A fibres were polysynaptic. The constant latency and regularity of the C response suggested monosynaptic connections. Low intensity stimulation of inhibitory inputs elicited a short-lived i.p.s.p. which increased in amplitude with increasing stimulus strength until it disappeared into a more prolonged hyperpolarization. This was associated with inhibition of background action potentials, and increased in duration with increasing stimulus strength up to C levels, indicating an A and C component. It is suggested that the level of excitability of these neurones depends on the relative amounts of concurrent noxious and innocuous stimulation, and that the resultant output, which is conveyed mainly to other neurones within the spinal cord, could modulate reflex action at the spinal level as well as affecting components of ascending sensory pathways.Supported by grant no. 11853/1.5 from the Wellcome Trust     

扬子鳄胸髓一氧化氮合酶和乙酰胆碱酯酶阳性神经元的分布

目的观察一氧化氮合酶(NOS)和乙酰胆碱酯酶(AChE)阳性神经元在扬子鳄胸髓的分布。方法采用还原型尼克酰胺腺嘌呤二核苷酸脱氢酶(NADPH-d)法和亚铁氰化铜法观察扬子鳄胸髓NOS和AChE阳性神经元的分布。结果扬子鳄胸髓前角、后角和中央灰质内可见NOS和AChE阳性神经元,白质内含有丰富的NOS和AChE阳性神经纤维。结论扬子鳄胸髓有NOS和AChE阳性神经元分布。     

NO and cGMP facilitate adenosine production in rat hearts via activation of ecto-5′-nucleotidase

 We examined whether nitric oxide (NO), a possible cardioprotective substance, can increase the production of interstitial adenosine in the ventricular myocardium. A flexibly mounted microdialysis technique was used to measure the concentration of interstitial adenosine and to assess the activity of ecto-5′-nucleotidase in in vivo rat hearts. The microdialysis probe was implanted in the left ventricular myocardium of anesthetized rats and perfused with Tyrode solution containing adenosine 5′-monophosphate (AMP) at a rate of 1.0 μl min^–1. The concentration of adenosine in the effluent (dialysate) was measured by high-performance liquid chromatography. Dialysate adenosine obtained during perfusion with the AMP-containing solution through the probe originated from the hydrolysis of AMP by endogenous ecto-5′-nucleotidase, and the level of adenosine reflected the activity of ecto-5′-nucleotidase in the tissue. S-Nitroso-N-acetylpenicillamine (SNAP, 0.3–3 mM), an NO donor, increased the dialysate adenosine measured in the presence of AMP (100 μM) in a concentration-dependent manner. However, in the presence of an NO-oxidizing agent, 2-(4-carboxyphenyl-4,4,5,5-tetramethylimidazoline)-1-oxyl 3-oxide (carboxy-PTIO, 1 mM), the effect of SNAP was abolished. Another NO donor, (±)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK409, 1 mM) also increased adenosine production. 8-Bromo-cGMP (0.1–3 mM), a membrane-permeable cGMP analogue and a potent activator of cGMP-dependent protein kinase, increased the level of AMP-primed dialysate adenosine in a concentration-dependent manner. These results suggest that NO facilitates the production of interstitial adenosine in rat hearts in situ, via cGMP-mediated activation of ecto-5′-nucleotidase. Received: 20 February 1998 / Received after revision and accepted: 9 July 1998     

Sulfide silver architectonics of the rat, cat, and guinea pig spinal cord

Summary The distribution of heavy metals in the spinal cord of the cat, rat, and guinea pig has been studied histochemically with Timm's sulfide silver method. There was considerable variation in the degree of staining of the neuropil. The dorsal horn showed a laminar staining pattern corresponding to the cytoarchitectonic lamination. Lamina I in the cat and guinea pig was light. Lamina II in all three species was heavily stained. In the rat and guinea pig it could be subdivided in a ventral and a dorsal layer, and moreover in the rat a darkly staining borderzone abutting on lamina III was present. Lamina III, characterized by heterogeneous staining, also appeared dark, although less obvious in the guinea pig. In the ventral horn the coarser stained particles in lamina IX contrasted with the surrounding lamina.Cell staining varied between different cell groups, and within single cell populations. In the cat thoracic cord the cells in nucleus intermedio-lateralis (IL) and nucleus intercalatus (IC) stained very weakly. In Clarke's column and in the motoneuron area cells, uniform in Nissl preparations, could be seen different after Timm staining.The results are discussed in relation to other histochemical patterns, cytoarchitectonics, and terminal fields of afferents. Considerable correlation of the Timm pattern to these data was found.     

Thermosensory defects after cervical spinal cord lesions in the cat

Summary The behavioural thermosensitivity of cat paws was examined before and/or after restricted uni- and/or bilateral lesions had been made in the spinal cord between the first and fifth cervical segments. Unilateral lesions of the lateral funiculus, which involved at least its whole width at the level of the central canal, reproducibly were found to interfere with the contralateral sensitivity for temperature increases and/or decreases. No corresponding thermosensory deficiencies were found after unilateral lesions involving the ventral spinal quadrant or the dorsal funiculus. Various bilateral and combined lesions were made, but no cat ever developed thermoanaesthesia. The bilateral lesions included bilateral transections of: the middle parts of the lateral funiculi, the dorsal halves of the lateral funiculi, the dorsal funiculi, and the ventral spinal half.Most of our knowledge about peripheral behavioural thermosensitivity after spinal cord injury is based on observations of human patients, especially after anterolateral chordotomies. The present finding of contralateral thermosensory deficiencies after lesions of the middle part of the lateral funiculus fits with some of the clinical reports. The present failure to cause thermoanaesthesia, on the other hand, is inconsistent with the theory of a single ascending spinal pathway for behavioural thermo-sensitivity, which has emanated mainly from the clinical observations.     

The role of inducible nitric oxide synthase following spinal cord injury in rat

Acute spinal cord injury (SCI) is two-step process that first involves the primary mechanical injury and then the secondary injury is induced by various biochemical reactions. Apoptosis is one of secondary SCI mechanisms and it is thought to play an important role for the delayed neuronal injury. The enhanced formation of nitric oxide (NO) via inducible nitric oxide synthase (iNOS) has been implicated in the pathogenesis of apoptosis in SCI. The level of .iNOS mRNA peaked at 6 hr after SCI and it declined until 72 hr after SCI in a rat model. Double-immunofluorescence staining revealed that iNOS positive cells were stained for ED-1, synaptophysin, GFAP, and oligodendrocyte marker. The terminal deoxynucleotidyl-transferase-mediated dUDP-biotin nick end-labeling (TUNEL) positive cell count was higher for the 72 hr post-SCI group than for the 24 hr post-SCI group. This cell count was also higher going in the caudal direction than in the rostral direction from the epicenter, and especially for the 72 hr group. Treatment with a selective iNOS inhibitor resulted in the reduction of TUNEL-positive cells at the lesion site. These findings suggest that nitric oxide generated by the iNOS of macrophages, neurons, oligodentrocytes, and astrocytes plays an important role for the acute secondary SCI that results from apoptotic cell death.     

Phosphorylation of c-Jun N-terminal kinase isoforms and their different roles in spinal cord dorsal horn and primary somatosensory cortex

The present study was undertaken to investigate whether isoforms of c-Jun N-terminal kinase (JNK 46 kDa and 54 kDa), one component of the mitogen-activated protein kinase (MAPK) family, might show region-related differential activation patterns in both naïve and pain-experiencing rats. In naïve rats, no significant difference was observed in total expression level of the two JNK isoforms between spinal cord and primary somatosensory cortex (S1 area). However, phosphorylated JNK 46 kDa was normally expressed in the S1 area, but not in the spinal cord, while neither of the two structures contained phosphorylated JNK 54 kDa. Subcutaneous bee venom (BV)-induced persistent pain stimulation resulted in a significant increase in the phosphorylation of both JNK isoforms in each area for a long period (lasting at least 48 h). Nevertheless, JNK 46 kDa exhibited a much higher activation than JNK 54 kDa in the spinal cord, whereas the same noxious stimulation elicited evident activation of JNK 54 kDa in the S1 area, leaving JNK 46 kDa less affected. Intraplantar injection of sterile saline solution, causing acute and transient pain, produced almost the same changes in activation profile of the two JNK isoforms as found in the BV-treated rats. These results implicate that individual members of the JNK family may be associated with specific regions of nociceptive processing. Also, the two JNK isoforms are supposed to function differently according to their locations within the rat central nervous system.     

Evidence for respiratory interneurones in the C3-C5 cervical spinal cord in the decorticate rabbit

Summary In mammals, it has long been considered that the bulbo-spinal inspiratory drive provided a direct (monosynaptic) excitation of phrenic motoneurones (Phr Mns). Although such connections have been demonstrated, recent indirect data strongly suggested that the main inspiratory drive is polysynaptic. We tried to directly demonstrate relay respiratory interneurones at the C3–C6 spinal cord level where the Phr Mn pool is located. The experiments were performed on decorticate, unanaesthetized, bilaterally vagotomized and curarized rabbits and the firing pattern of spinal interneurones was compared to the phrenic bursting. Dorsally and dorso-medially to the Phr Mn pool, different classes of inspiratory (54%) and expiratory (46%) interneurones could be identified in the ventral horn. Three classes of inspiratory interneurones were characterized and classified as I all (26%), I late (43%) and I tonic (29%) according to the terminology used by other authors for the bulbospinal inspiratory neurones which drive the spinal respiratory motoneurones. The expiratory interneurones could also be divided into 3 classes: E all (48%), E late (10%) and E tonic (41%). This first direct evidence of inspiratory interneurones at the C3–C6 spinal cord levels can account for the major polysynaptic excitation of the Phr Mns while the presence of numerous expiratory interneurones at this level suggests a polysynaptic bulbo-spinal inhibitory action onto the Phr Mns. These classes of inspiratory and expiratory interneurones did not always coincide with the bulbo-spinal classes of neurones described elsewhere. Unless these discrepancies are due to the different experimental conditions, they may indicate that some of these interneurones are not just relay target cells and they suggest that they might behave as integrative operators between the medullary drive and the Phr Mns.     

Dynamic changes in the receptive field properties of spinal cord neurons with ankle input in rats with chronic unilateral inflammation in the ankle region

Summary The aim of this study was to determine the discharge and receptive field properties of spinal cord neurons with ankle input in spinal segments L4-6 in the rat, both under control conditions and during the course of an adjuvant-induced unilateral inflammation in the ankle. The extent of receptive fields in the skin and deep tissue was assessed using brush, pinch and compression stimuli. Neurons were categorized as nociceptive-specific or wide-dynamic-range neurons on the basis of their response thresholds and responses to suprathreshold stimuli. At all stages of inflammation (2, 6, 13 and 20 days post inoculation) the population of neurons with ankle input showed differences from the population of neurons with ankle input in control rats. There was a reduction in the number of neurons that appeared as nociceptive specific and a concomitant increase in the number of neurons showing a wide-dynamic-range response profile. The receptive fields of the neurons with ankle input were markedly larger in rats with inflammation in the ankle region and mainly spread proximally on the ipsilateral hindlimb and also to the abdomen and tail in some cases. There was also an increase in the number of neurons with contralateral excitatory inputs. The mechanical thresholds at the ankle joint and proximal parts of the ipsilateral hindlimb were less in arthritic rats than in controls. The proportion of spontaneously active neurons was also increased in rats during the initial and later stages of inflammation, although there was no significant increase in the mean spontaneous discharge frequency. These data show that there are long-term changes in the receptive field and response properties of neurons in intact rats with chronic unilateral adjuvant-induced inflammation similar to those described previously in spinal cats with acute inflammation (Neugebauer and Schaible 1990). It is presumed that similar afferent and spinal mechanisms are at work under acute and chronic inflammatory conditions which produce hyperexcitability in spinal neurons with joint input.     

Autoradiographic identification of estradiol-concentrating cells in the spinal cord of the female rat

Summary The topography and number of estradiol (E)-concentrating cells in the lower lumbar and sacral segments of the spinal cord of the female rat have been examined by the steroid autoradiography method. A nuclear-saturating dose of E was administered by intravenous infusion, which kept blood estrogen at or above proestrus levels for 3.5–4 h, much longer than usual for steroid receptor studies. The cord segments selected for examination are known to receive somatosensory information relevant for estrogen-dependent behavior, and to contain some of the motoneurons for epaxial muscles responsible for this behavior.Small numbers of E-concentrating cells were found in the dorsal portion of the gray matter of L₄, L₅, L₆ and the sacral segments. These cells were found in lamina II, in the midline region which includes lamina X, and the medial portions of laminae III, IV, and V when they cross in the midline. E-concentrating cells were also found in the lateral portions of laminae III, IV, and V, and in lamina VII. Virtually no E-concentrating cells were found in the ventral portion of the gray matter or in the white matter. The spinal cord had few E-concentrating cells compared to the hypothalamus.Supported in part by NIH grant HD-10655     

Spantide抑制大鼠甲醛试验中脊髓中央管周围区域NOS表达的上调(英文)

目的：本实验观察非选择性NK受体拮抗剂［D-Arg1, D-Trp7,9, Leu11］-substance P (spantide)对大鼠甲醛实验诱导的脊髓中央管周围灰质区域NOS表达的影响。 方法： 右后掌足底皮下注射甲醛(5%，0.2 mL)诱导持续性痛及痛过敏，用缩足反射实验测定大鼠痛反应。应用NADPH-d组织化学法观察NOS的表达。Spantide于甲醛注射前5 min经L5-L6腰椎间隙鞘内注射。 结果： (1)足底注射甲醛引起大鼠疼痛行为反应，包括抓、咬、舔、注射侧后爪抬离盒底等。伴随着这些行为反应，脊髓L5节段中央管周围灰质区(第X板层)NOS表达上调。(2)预先给予spantide能抑制大鼠甲醛试验第二时相注射侧肢体的自发性退缩反射，同时抑制了脊髓中央管周围灰质区NOS表达的上调。 结论： SP在大鼠甲醛试验中脊髓中央管周围区域NOS表达上调中起着重要的作用。