ORCID Profile
0000-0003-0755-8747
Current Organisation
University of New South Wales
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Springer Science and Business Media LLC
Date: 08-1988
DOI: 10.1007/BF01189802
Publisher: Elsevier
Date: 2008
Publisher: Wiley
Date: 09-1998
DOI: 10.1111/J.1469-7793.1998.461BH.X
Abstract: 1. The patterns of on-going synaptic events recorded intracellularly in neurones of superior cervical ganglia (SCG)of anaesthetized female rats were analysed by constructing inter-event interval histograms, autocorrelograms, ln-survivor curves and histograms triggered by the arterial pulse wave and by the intercostal EMG. 2. In 11/12 cells with on-going frequencies > 0.5 Hz, one or two inputs were strong (i.e. always suprathreshold). In five cells, action potentials also arose from synaptic potentials with litudes close to threshold. 3. Synaptic events in 5/11 neurones tested were phase-related to the arterial pressure wave (i.e. had cardiac rhythmicity, CR). 4. Synaptic events in 9/10 neurones tested (including all with CR) were phase-related to the intercostal EMG and/or their autocorrelograms showed peaks at multiples of the respiratory interval (i.e. had respiratory rhythmicity, RR). 5. The intervals between all synaptic events were exponentially distributed in 8/12 neurones although intervals between single strong events showed peaks related to the respiratory cycle. Bursts occurred only by chance. 6. Event patterns could be simulated by combining events from several respiration-modulated inputs with their timing distributed over nearly half the cycle. From the simulations, the mean number of active preganglionic inputs was estimated to be approximately 6 with mean discharge frequency approximately 0.4 Hz. 7. We conclude that, in the spontaneously breathing anaesthetized rat, most preganglionic neurones to the SCG fire with relatively low probability in relation to the respiratory cycle. Rhythms in a postganglionic neurone reflect the activity of its suprathreshold preganglionic inputs.
Publisher: Springer Science and Business Media LLC
Date: 15-04-1997
DOI: 10.1007/PL00004991
Abstract: The effects of catechol on membrane properties in lumbar sympathetic postganglionic neurones isolated from guinea-pigs were studied in vitro in current and voltage cl using single intracellular microelectrodes. Neurones with properties characteristic of two previously described classes of neurone (phasic and tonic) were studied. Catechol (3-12 mM) produced a few mV depolarization and a dose-dependent increase in membrane resistance which were both larger in tonic than in phasic neurones. In the presence of catechol, both phasic and tonic neurones fired only a single action potential at the beginning of a maintained depolarizing current step. In both neurone types, catechol reduced action potential litude and slowed its time course. The peak of the afterhyperpolarization became delayed and reduced in litude, particularly in tonic neurones. The time constant of inactivation of IA was reduced by catechol without change in the voltage sensitivity of activation or inactivation: IC50 was 3 mM in phasic and 4 mM in tonic neurones. Catechol also blocked a slow voltage-activated K+ current (resembling ID) that was present in many tonic neurones. Catechol did not modify the slow calcium-activated potassium current (gKCa1) or the anomalous rectifier neither did it appear to affect the fast calcium-activated potassium current (IC) or the delayed rectifier. Catechol did not change the overall rate of spontaneous synaptic activity nor enhance the release of quanta of ACh from preganglionic terminals evoked by nerve stimulation. We conclude that, in addition to blocking IA, catechol blocks the slow ID-like current in sympathetic neurones. It also has a profound effect on the action potential probably by increasing inactivation of voltage-dependent Na+ channels. The change from tonic to phasic discharge in tonic neurones cannot be attributed solely to its effects on IA.
Publisher: Wiley
Date: 2010
Publisher: S. Karger AG
Date: 2005
DOI: 10.1159/000086886
Abstract: Hypertrophy of the perivascular plexus is thought to play a role in the development of hypertension in spontaneously hypertensive rats (SHR). However, it is not known whether the sympathetic varicosities are more numerous or larger, or form more neurovascular junctions. Further, a parallel hypertrophy of primary afferent terminals around the vessels might modulate any effects of hypertrophied sympathetic terminals. We have investigated the perivascular plexus around second-order mesenteric arteries of SHR and Wistar-Kyoto (WKY) rats by electron microscopy. Noradrenergic terminals were identified by the presence of small granular vesicles after chromaffin fixation, and substance P (SP+) afferent axons were identified by immunohistochemistry. The numbers of noradrenergic axon and varicosity profiles were higher (48 and 25%, respectively) in SHR than in WKY rats, and the majority lay closer to the medio-adventitial border. In contrast, there was no difference in the numbers of SP+ axons. Sympathetic and SP+ varicosities were indistinguishable in size, shape, vesicle content and mitochondrion content between each other and between the strains. However, both the number of neuromuscular junctions and the proportion of varicosities that formed them in SHR arteries were more than double those in WKY vessels. The data clearly show that hyperinnervation in SHR is specific for noradrenergic axons.
Publisher: Elsevier BV
Date: 12-2003
Publisher: American Physiological Society
Date: 02-2011
DOI: 10.1152/AJPHEART.00834.2010
Abstract: We have investigated the recovery of sympathetic control following reinnervation of denervated rat tail arteries by relating the reappearance of noradrenergic terminals to the litude of nerve-evoked contractions of isometrically mounted artery segments in vitro. We have also assessed reactivity to vasoconstrictor agonists. Freezing the collector nerves near the base of the tail in adult rats denervated the artery from ∼40 mm along the tail. Restoration of the perivascular plexus declined along the length of the tail, remaining incomplete for mo. After 4 mo, nerve-evoked contractions were prolonged but of comparable litude to control at ∼60 mm along the tail they were smaller at ∼110 mm. At ∼60 mm, facilitation of contractions to short trains of stimuli by the norepinephrine transporter blocker, desmethylimipramine, and by the α 2 -adrenoceptor antagonist, idazoxan, was reduced in reinnervated arteries. Blockade of nerve-evoked contractions by the α 1 -adrenoceptor antagonist, prazosin, was less and by idazoxan greater than control after 8 wk but similar to control after 16 wk. Sensitivity of reinnervated arteries to the α 1 -adrenoceptor agonist, phenylephrine, was raised in the absence but not in the presence of desmethylimipramine. Sensitivity to the α 2 -adrenoceptor agonist, clonidine, was maintained in 16-wk reinnervated arteries when it had declined in controls. Thus regenerating sympathetic axons have a limited capacity to reinnervate the rat tail artery, but nerve-evoked contractions match control once a relatively sparse perivascular plexus is reestablished. Functional recovery involves prolongation of contractions and deficits in both clearance of released norepinephrine and autoinhibition of norepinephrine release.
Publisher: American Physiological Society
Date: 05-2003
Abstract: The electrotonic behavior of three phenotypes of sympathetic postganglionic neuron has been analyzed to assess whether their distinct cell input capacitances simply reflect differences in morphology. Because the distribution of membrane properties over the soma and dendrites is unknown, compartmental models incorporating cell morphology were used to simulate hyperpolarizing responses to small current steps. Neurons were classified as phasic (Ph), tonic (T), or long-afterhyperpolarizing (LAH) by their discharge pattern to threshold depolarizing current steps and filled with biocytin to determine their morphology. Responses were simulated in models with the average morphology of each cell class using the program NEURON. Specific membrane resistivity, R m , was derived in each model. Fits were acceptable when specific membrane capacitance, C m , and specific resistivity of the axoplasm, R i, were varied within realistic limits and when underestimation of membrane area due to surface irregularities was accounted for. In all models with uniform R m , solutions for R m that were the same for all classes could not be found unless C m or R i were different for each class, which seems unrealistic. Incorporation of a small somatic shunt conductance yielded values for R m for each class close to those derived assuming isopotentiality ( R m approximately 40, 27, and 15 kΩcm 2 for T, Ph, and LAH neurons, respectively). It is concluded that R m is distinct between neuron classes. Because Ph and LAH neurons relay selected preganglionic inputs directly, R m generally affects function only in T neurons that integrate multiple subthreshold inputs and are modulated by peptidergic transmitters.
Publisher: Oxford University Press (OUP)
Date: 04-2008
DOI: 10.1111/J.1526-4637.2007.00290.X
Abstract: Cutaneous application of menthol in healthy subjects induces cold allodynia via sensitization of cold-sensitive nociceptors. We investigated the effects of menthol on preexisting cold allodynia in patients to test whether the allodynia was exacerbated. In eight neuropathic pain patients (six of peripheral, two of central origin), 40% menthol was applied topically to an area of preexisting cold allodynia. Mirror-image skin areas and aged-matched healthy subjects served as controls in patients with unilateral and bilateral neuropathic pain, respectively. Prior to and after menthol, cold pain thresholds were measured using a thermotest device. Menthol induced significant cold allodynia in control areas. However, in neuropathic areas, results were more heterogeneous. Overall, preexisting cold allodynia was not aggravated by topical menthol and was attenuated in 6/8 patients. These results suggest that, unlike in controls, menthol is not more hyperalgesic, but may be analgesic in some patients with peripheral and central neuropathic pain.
Publisher: Elsevier
Date: 2006
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-08-2004
DOI: 10.1097/01.WNR.0000135700.52904.77
Abstract: Macrophages and T-lymphocytes invade the spinal cord in and around a lesion and spinal microglia are converted into macrophages. After spinal transection at T8 in rats, T-lymphocyte and major histocompatibility complex II+ (MHC II+) macrophage numbers were increased within dorsal root ganglia (DRGs) below the lesion. Inflammation was greater in DRGs closer to the site of transection. After 8 weeks, MHC II+cell density had fallen by 30% but T-lymphocyte numbers were undiminished. In lumbosacral DRGs, inflammation preceded inflammation within the spinal cord. The responses in distant DRGs are hard to reconcile with the limited damage to sensory neurons produced by the lesion. Inflammation of DRGs after spinal injury may contribute to hyper-reflexia and pain.
Publisher: Springer Science and Business Media LLC
Date: 30-01-2007
Publisher: Wiley
Date: 30-04-2013
Publisher: Wiley
Date: 23-07-2001
DOI: 10.1002/CNE.1276
Abstract: The dorsal commissural nucleus (DCN) in the lumbosacral spinal cord receives afferent inputs from the pelvic organs via pudendal and pelvic nerves. Electrophysiological and morphological properties of neurons in the DCN of L6-S1 were examined using whole-cell recordings with biocytin-filled electrodes in transverse slices of mature rat spinal cord. Neurons were categorized into three groups according to their discharge in response to suprathreshold depolarizing pulses neurons with tonic (19/42) and phasic (13/42) firing patterns, and neurons (10/42) that fired in bursts arising from a Ca(2+)-dependent hump. The predominantly fusiform somata of neurons labeled during recording (n = 31) had on average 3.1 primary dendrites, 7.5 terminating dendritic branches, 3.1 axon collaterals, and 14.2 axon terminations per neuron. The groups were morphologically distinct on the basis of their dendritic branching patterns. Phasic neurons (n = 10) had the most elaborate dendritic branching and the largest numbers of axon collaterals. All tonic neurons (n = 11) had axons/collaterals projecting to the intermediolateral area but none to the funiculi, suggesting that they function as interneurons in local autonomic reflexes. Many axons/collaterals of all phasic neurons lay within the DCN, suggesting that they integrate segmental and descending inputs. Seven of 10 neurons with Ca(2+)-dependent humps had axons/collaterals extending into one of the funiculi, suggesting that they project intersegmentally or to the brain. Ca(2+) hump neurons also had more axons/collaterals within the DCN and fewer in the intermediolateral area than tonic neurons. This correlation between firing pattern and morphology is an important step toward defining the cellular pathways regulating pelvic function.
Publisher: Springer Science and Business Media LLC
Date: 06-1993
DOI: 10.1038/363543A0
Abstract: In humans, trauma to a peripheral nerve may be followed by chronic pain syndromes which are only relieved by blockade of the effects of sympathetic impulse traffic. It is presumed that, after the lesion, noradrenaline released by activity of sympathetic postganglionic axons excites primary afferent neurons by activating alpha-adrenoceptors, generating signals that enter the 'pain pathways' of the central nervous system. The site of coupling is unclear. In some patients local anaesthesia of the relevant peripheral nerve does not alleviate pain, implying that ectopic impulses arise either within the central nervous system, or in proximal parts of the primary afferent neurons. In experimentally lesioned rats, activity can originate within the dorsal root ganglia. Here we report that, after sciatic nerve ligation, noradrenergic perivascular axons in rats sprout into dorsal root ganglia and form basket-like structures around large-diameter axotomized sensory neurons sympathetic stimulation can activate such neurons repetitively. These unusual connections provide a possible origin for abnormal discharge following peripheral nerve damage. Further, in contrast to the sprouting of intact nerve terminals into nearby denervated effector tissues in skin, muscle, sympathetic ganglia and sweat glands, the axons sprout into a target which has not been partially denervated.
Publisher: Wiley
Date: 10-1998
DOI: 10.1111/J.1469-7793.1998.211BF.X
Abstract: 1. Extracellular recording techniques have been used to study nerve impulses in single sensory nerve terminals in guinea-pig cornea isolated in vitro. 2. Nerve impulses occurred spontaneously and were evoked by electrical stimulation of the ciliary nerves. 3. The nerve impulses were identified as originating in polymodal receptors, mechano-receptors or 'cold' receptors. All three types are believed to be nociceptors. 4. Tetrodotoxin (TTX, 1 microM) blocked nerve impulses evoked by electrical stimulation of the ciliary nerves. However, ongoing and/or naturally evoked nerve impulses persisted in the presence of TTX in all three types of receptors. Lignocaine (lidocaine 1 mM) blocked all electrical activity. 5. TTX-resistant sodium channels therefore play a major role in generating the action potentials that signal pain to the brain.
Publisher: Wiley
Date: 05-1997
DOI: 10.1111/J.1469-7793.1997.165BO.X
Abstract: 1. Synaptic events evoked by brief noxious cutaneous stimuli were recorded in sympathetic neurones in the superior cervical ganglion of anaesthetized rats. 2. On-going excitatory synaptic potentials (ESPs) and/or action potentials (APs) were recorded in 69% of neurones at mean frequencies that varied from 0.01 to 6.3 Hz in different cells. From histograms of ESP litude during membrane hyperpolarization, it appears that most cells received one (52%), or two or more (36%), suprathreshold inputs and several subthreshold inputs with overlapping litudes. 3. Pinching the skin for 1-3 s evoked either a brief burst of synaptic events (lasting about 300 ms) preceding a few seconds of inhibition (burst-inhibitory (BI) neurones), or simply an excitation (excitatory (E) neurones), or no response (O neurones). In 60% of BI neurones, a second burst occurred after the end of the pinch. 4. BI neurones had a higher frequency of on-going synaptic activity (2.9 +/- 0.5 Hz, n = 15) than E neurones (0.2 +/- 0.1 Hz, n = 5) or O (0.2 +/- 0.1 Hz, n = 5) neurones. Most neurones with two or more suprathreshold inputs were BI neurones. In 20% of neurones (all BI with high rates of synaptic activity), several other inputs had ESPs with litudes close to threshold. 5. Subthreshold and suprathreshold inputs responded in the same way in only 45% of neurones, but suprathreshold inputs were excited in 73% of BI and all E neurones. The order of recruitment of different inputs varied from trial to trial. If classification was based only on suprathreshold responses, there were 36% BI, 32% E and 32% O neurones. 6. In the majority of neurones, postganglionic discharge was initiated exclusively by suprathreshold inputs, even during reflex excitation. 7. Qualitatively similar, but smaller, responses were evoked by a puff of air on the abdomen in 71% of cells tested. 8. The data suggest that the natural discharge of SCG neurones is largely determined by the activity of one or two preganglionic inputs with high quantal contents. BI neurones may include vasoconstrictor neurones, whereas the other types include secretomotor, pilomotor and other neurones projecting to targets in the head.
Publisher: American Physiological Society
Date: 2006
DOI: 10.1152/AJPHEART.00712.2005
Abstract: In patients with high thoracic spinal lesions that remove most of the central drive to splanchnic preganglionic neurons, visceral or nociceptive stimuli below the lesion can provoke large increases in blood pressure (autonomic dysreflexia). We have examined the effects of T 4 spinal transection on isometric contractions of mesenteric arteries isolated from spinalized rats. Nerve-evoked contractions involved synergistic roles for norepinephrine and ATP. At 7 wk after spinal transection, responses to perivascular stimulation at 1–5 Hz were enhanced fivefold, whereas the α 1 -adrenoceptor antagonist prazosin (10 nM) produced a twofold larger reduction in contraction (to 20 pulses at 10 Hz) than in unoperated controls. In contrast, the reduction in nerve-evoked contractions by the P2-purinoceptor antagonist suramin (0.1 mM) and the responses to the P2-purinoceptor agonist α,β-methylene ATP or to high K + concentration did not greatly differ between groups, indicating that arteries from spinalized rats were not generally hyperreactive. Sensitivity to the α 1 -adrenoceptor agonist phenylephrine was enhanced in arteries from spinalized rats, and the difference from controls was abolished by the norepinephrine uptake blocker desmethylimipramine. Sensitivity to the α 1 -adrenoceptor agonist methoxamine, which is not a substrate for the neuronal norepinephrine transporter, was similar among the groups. Thus the increased neurally evoked response after spinal transection appeared to be due to a reduction in neuronal uptake of released norepinephrine, a mechanism that did not explain the enhanced response of tail arteries after spinal transection that we previously reported. The findings provide further support for potentiated neurovascular responses contributing to the genesis of autonomic dysreflexia.
Publisher: Wiley
Date: 05-1999
DOI: 10.1046/J.1460-9568.1999.00589.X
Abstract: Injury to a peripheral nerve induces in the dorsal root ganglia (DRG) sprouting of sympathetic and peptidergic terminals around large-diameter sensory neurons that project in the damaged nerve. This pathological change may be implicated in the chronic pain syndromes seen in some patients with peripheral nerve injury. The mechanisms underlying the sprouting are not known. Using in situ hybridization and immunohistochemical techniques, we have now found that nerve growth factor (NGF) and neurotrophin-3 (NT3) synthesis is upregulated in satellite cells surrounding neurons in lesioned DRG as early as 48 h after nerve injury. This response lasts for at least 2 months. Quantitative analysis showed that the levels of mRNAs for NT3 and NGF increased in ipsilateral but not contralateral DRG after nerve injury. Noradrenergic sprouting around the axotomized neurons was associated with p75-immunoreactive satellite cells. Further, antibodies specific to NGF or NT3, delivered by an osmotic mini-pump to the DRG via the lesioned L5 spinal nerve, significantly reduced noradrenergic sprouting. These results implicate satellite cell-derived neurotrophins in the induction of sympathetic sprouting following peripheral nerve injury.
Publisher: Wiley
Date: 26-11-2004
Publisher: Wiley
Date: 04-2004
Publisher: Oxford University Press (OUP)
Date: 07-2013
Publisher: Mary Ann Liebert Inc
Date: 05-2011
Abstract: Despite reduced sympathetic activity below the level of a spinal cord injury (SCI), venoconstriction during autonomic dysreflexia increases venous return to the heart. Here, contractions of isometrically mounted tail veins from rats with spinal transection at T4 performed 8 - 10 weeks earlier are compared with those from sham-operated rats. After SCI, lumen diameter was reduced by ∼30% and the contractions evoked by electrical stimulation of the perivascular axons were larger than control. This augmentation of neurovascular transmission was not associated with enhanced sensitivity to α-adrenoceptor agonists or to adenosine-5'-triphosphate (ATP) although contractions to depolarization with K(+) were larger after SCI. The percentage reduction in nerve-evoked contraction after SCI produced by the α(1)-adrenoceptor antagonist prazosin (10 nM) was unchanged but that by the α(2)-adrenoceptor antagonist rauwolscine (0.1 μM) was reduced. The relative contribution of P2-purinoceptors to nerve-evoked contractions after α-adrenoceptor blockade, revealed by adding suramin (0.1 mM), was unchanged. The greater depolarization-induced contraction and the reduced contribution of α(2)-adrenoceptors to nerve-evoked contraction suggest that changes in the venous smooth muscle underlie the potentiation of neurovascular transmission after SCI. Furthermore, the smaller lumen diameter after SCI will increase the pressure that the veins exert on the luminal contents when they are neurally activated.
Publisher: Informa UK Limited
Date: 1995
DOI: 10.3109/10641969509087076
Abstract: The electrophysiological properties of pre- and postganglionic neurones and their synaptic inputs have been examined in both in vivo and in vitro preparations. Electrically, both neurone types have similar low resting conductance and compact dendritic trees. In preganglionic vasoconstrictor neurones, both slow and fast excitatory and fast inhibitory potentials are probably involved in baroreceptor reflexes, discharge being initiated after summation. In contrast, postganglionic vasoconstrictor neurones receive only one type of fast excitatory input. One of the converging preganglionic inputs has a very high safety factor and always fires the postganglionic neurone ensuring that the centrally-derived pattern of discharge reaches the neurovascular junctions. We do not know if the other subthreshold inputs summate during natural activity in vivo, as it is not known whether functionally distinct preganglionic inputs converge on vasoconstrictor neurones in ganglia.
Publisher: Elsevier BV
Date: 05-2014
DOI: 10.1016/J.AUTNEU.2013.12.009
Abstract: Following a peripheral nerve injury, a sterile inflammation develops in sympathetic and dorsal root ganglia (DRGs) with axons that project in the damaged nerve trunk. Macrophages and T-lymphocytes invade these ganglia where they are believed to release cytokines that lead to hyperexcitability and ectopic discharge, possibly contributing to neuropathic pain. Here, we examined the role of the sympathetic innervation in the inflammation of L5 DRGs of Wistar rats following transection of the sciatic nerve, comparing the effects of specific surgical interventions 10-14 days prior to the nerve lesion with those of chronic administration of adrenoceptor antagonists. Immunohistochemistry was used to define the invading immune cell populations 7 days after sciatic transection. Removal of sympathetic activity in the hind limb by transecting the preganglionic input to the relevant lumbar sympathetic ganglia (ipsi- or bilateral decentralization) or by ipsilateral removal of these ganglia with degeneration of postganglionic axons (denervation), caused less DRG inflammation than occurred after a sham sympathectomy. By contrast, denervation of the lymph node draining the lesion site potentiated T-cell influx. Systemic treatment with antagonists of α1-adrenoceptors (prazosin) or β-adrenoceptors (propranolol) led to opposite but unexpected effects on infiltration of DRGs after sciatic transection. Prazosin potentiated the influx of macrophages and CD4(+) T-lymphocytes whereas propranolol tended to reduce immune cell invasion. These data are hard to reconcile with many in vitro studies in which catecholamines acting mainly via β2-adrenoceptors have inhibited the activation and proliferation of immune cells following an inflammatory challenge.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-1999
Publisher: Wiley
Date: 06-07-2010
DOI: 10.1111/J.1476-5381.2010.00873.X
Abstract: British Journal of Pharmacology (BJP) is pleased to publish a new set of guidelines for reporting research involving animals, simultaneously with several other journals the ‘ARRIVE’ guidelines (Animals in Research: Reporting In Vivo Experiments). This editorial summarizes the background to the guidelines, gives our view of their significance, considers aspects of specific relevance to pharmacology, re‐states BJP's guidelines for authors on animal experiments and indicates our commitment to carrying on discussion of this important topic. We also invite feedback via the British Pharmacological Society website.
Publisher: Elsevier BV
Date: 11-1975
DOI: 10.1016/0006-8993(75)90017-7
Abstract: Different-size species of phi X174-specific mRNA's decayed exponentially, with half-lives ranging from 4.5 to 11 min.
Publisher: Elsevier BV
Date: 11-1992
DOI: 10.1016/0165-1838(92)90121-V
Abstract: The autonomic nervous system supplies each type of target organ via separate pathways which consist of sets of pre- and postganglionic neurones with distinct patterns of reflex activity. This has been firmly established for the lumbar sympathetic nervous system to skin, skeletal muscle and viscera, for the thoracic sympathetic outflow to the head and for several parasympathetic systems. In principle, that was already known by Langley. The specificity of the messages that these pathways transmit from the central nervous system arises from integration within precisely organized pathways in the neuraxis. The messages travel along discrete functional pathways and are transmitted to the target tissues via close neuroeffector junctions. Integration in the periphery occurs within each pathway, both in ganglia and at the level of the effector organs. We still need to understand how the central messages get through without distortion and how they control the erse functions of the vasculature and viscera.
Publisher: Elsevier BV
Date: 06-2002
DOI: 10.1016/S0306-4522(02)00065-9
Abstract: The distribution of major histocompatibility complex class II (MHC II)-positive non-neuronal cells and T-lymphocytes was examined immunohistochemically in dorsal root ganglia (DRGs) up to 12 weeks following transection of one sciatic or lumbar spinal nerve in adult rats. Unlike within the brain, MHC II immunopositive (+) and T-cells are normally present within DRGs. After nerve transection, MHC II+ cell density increased (by about four times after each lesion) in DRGs projecting into lesioned nerves. Subsequently the number declined after sciatic but not spinal nerve transection. MHC II+ cells did not contain glial markers, even when these were up-regulated after the lesions. Initially, MHC II+ cells lay outside the satellite glia but, by 11 weeks, they had moved through them to lie against the somata. T-cells invaded the lesioned DRGs earlier than the MHC II+ cells. They achieved greater numbers after spinal (30 x control) than after sciatic (12 x control) nerve transection. They also increased in undamaged ganglia adjacent to the spinal nerve injury. T-cell density progressively declined after spinal but not sciatic nerve transection. Both cell types appeared to invade the DRGs initially through blood vessels and the meninges, particularly near the subarachnoid angle. At later stages, occasional neurones had dense aggregations of T-cell receptor+ and MHC II+ cells associated with them. We conclude that the magnitude and time course of changes in MHC II expression and T-cell numbers in lesioned DRGs differ from the responses within motor nuclei after axotomy. The influx of inflammatory cells may contribute to neurone survival in the short term. Their long-term presence has implications for patients. These cells have the potential to release excitatory cytokines that may generate ectopic impulse activity in sensory neurones after nerve injury and so may play a role in the generation of chronic neuropathic pain.
Publisher: Springer Science and Business Media LLC
Date: 08-1964
DOI: 10.1038/203874A0
Publisher: Wiley
Date: 05-2003
Publisher: Springer Science and Business Media LLC
Date: 07-2007
Publisher: Oxford University Press (OUP)
Date: 21-08-2008
DOI: 10.1093/BRAIN/AWN169
Abstract: Central neuropathic pain following lesions within the CNS, such as spinal cord injury, is one of the most excruciating types of chronic pain and one of the most difficult to treat. The role of spinothalamic pathways in this type of pain is not clear. Previous studies suggested that spinothalamic tract lesions are necessary but not sufficient for development of central pain, since deficits of spinothalamic function were equally severe in spinal cord injured people with and without pain. The aim of the present study was to examine spinothalamic tract function by quantitative sensory testing before and after activation and sensitization of small diameter afferents by applying menthol, histamine or capsaicin to the distal skin areas where spontaneous pain was localized. Investigations were performed in matched groups each of 12 patients with and without central pain below the level of a clinically complete spinal cord injury, and in 12 able-bodied controls. To test peripheral C fibre function, axon reflex vasodilations induced by histamine and capsaicin applications were quantified. In eight patients with pain, sensations of the same quality as one of their major in idual pain sensations were rekindled by heat stimuli in combination with topical capsaicin (n = 7) or by cold stimuli (n = 1). No sensations were evoked in pain-free patients (P < 0.01). Capsaicin-induced axon reflex vasodilations were significantly larger in pain patients with heat- and capsaicin-evoked sensations in comparison to pain patients without capsaicin-provoked sensations. These results suggest that intact thermosensitive nociceptive afferents within lesioned spinothalamic tract pathways distinguish people with central pain from those without. The ability to mimic chronic pain sensations by activation of thermosensory nociceptive neurons implies that ongoing activity in these residual spinothalamic pathways plays a crucial role in maintaining central pain. We propose that processes associated with degeneration of neighbouring axons within the tract, such as inflammation, may trigger spontaneous activity in residual intact neurons that act as a 'central pain generator' after spinal cord injury.
Publisher: Elsevier BV
Date: 07-2007
DOI: 10.1016/J.BBI.2006.10.013
Abstract: Chronic constriction injury (CCI) of the sciatic nerve in rodents produces mechanical and thermal hyperalgesia and is a common model of neuropathic pain. Here we compare the inflammatory responses in L4/5 dorsal root ganglia (DRGs) and spinal segments after CCI with those after transection and ligation at the same site. Expression of ATF3 after one week implied that 75% of sensory and 100% of motor neurones had been axotomized after CCI. Macrophage invasion of DRGs and microglial and astrocytic activation in the spinal cord were qualitatively similar but quantitatively distinct between the lesions. The macrophage and glial reactions around neurone somata in DRGs and ventral horn were slightly greater after transection than CCI while, in the dorsal horn, microglial activation (using markers OX-42(for CD11b) and ED1(for CD68)) was greater after CCI. In DRGs, macrophages positive for OX-42(CD11b), CD4, MHC II and ED1(CD68) more frequently formed perineuronal rings beneath the glial sheath of ATF3+ medium to large neurone somata after CCI. There were more invading MHC II+ macrophages lacking OX-42(CD11b)/CD4/ED1(CD68) after transection. MHC I was expressed in DRGs and in spinal sciatic territories to a similar extent after both lesions. CD8+ T-lymphocytes aggregated to a greater extent both in DRGs and the dorsal horn after CCI, but in the ventral horn after transection. This occurred mainly by migration, additional T-cells being recruited only after CCI. Some of these were probably CD4+. It appears that inflammation of the peripheral nerve trunk after CCI triggers an adaptive immune response not seen after axotomy.
Publisher: Elsevier BV
Date: 09-2017
Publisher: Springer Science and Business Media LLC
Date: 10-1991
DOI: 10.1007/BF01191730
Publisher: Mary Ann Liebert Inc
Date: 11-2010
Abstract: Sympathetic nerve-mediated contractions of mesenteric and tail arteries controlled by preganglionic neurones decentralized by a spinal cord injury (SCI) are potentiated, and likely contribute to autonomic dysreflexia. However, reactivity to the α(1)-adrenoceptor agonist phenylephrine has been reported to be enhanced in vascular beds controlled by preganglionic neurones lying both rostral and caudal to an SCI in vivo. Here responses of isometrically-mounted median and saphenous arteries isolated from rats 2 and 8 weeks after transection of the T4 spinal cord have been compared with those from sham-operated rats. After SCI, contractions of median arteries to perivascular nerve stimulation, to α-adrenoceptor agonists (phenylephrine and clonidine), to the P2X-purinoceptor agonist α,β-methylene ATP, and to 60 mM K(+) were unchanged. Blockade of nerve-evoked contractions by α-adrenoceptor antagonists (prazosin and idazoxan) was not affected by SCI in either the median or saphenous arteries. In contrast, at 2 and 8 weeks after SCI, nerve-evoked contractions of saphenous arteries were potentiated. Saphenous arteries were less sensitive to phenylephrine 8 weeks after SCI, and their contractions to 60 mM K(+) were reduced. However, the sensitivity of saphenous arteries to clonidine was unchanged by SCI. Eight weeks after SCI, the reactivity of saphenous arteries to α,β-methylene ATP was unchanged, but the P2-antagonist suramin produced more blockade of nerve-evoked contractions. These findings demonstrate that neurovascular transmission is enhanced in arteries located caudal, but not rostral, to a spinal transection. In the saphenous artery, the most likely explanation seems to be an increase in neurotransmitter release, as may occur in other inactive sympathetic pathways caudal to the lesion.
Publisher: Elsevier BV
Date: 07-2007
Publisher: Wiley
Date: 1999
DOI: 10.1111/J.1469-7793.1999.059AF.X
Abstract: 1. The involvement of different presynaptic Ca2+ channels in transmission at 'weak' (subthreshold) and 'strong' (suprathreshold) synapses was investigated in guinea-pig paravertebral ganglia isolated in vitro. Selective Ca2+ channel antagonists were used to block excitatory synaptic currents evoked by stimulating single preganglionic axons. 2. The N-type Ca2+ channel blocker, omega-conotoxin GVIA (100 nM), reduced peak synaptic conductance by similar amounts at weak synapses (by 39 +/- 6 %) and strong synapses (34 +/- 6 %). 3. The P-type Ca2+ channel blocker, omega-agatoxin IVA (40 nM), significantly reduced transmitter release at weak synapses (by 42 +/- 6 %) but had only a small effect at strong synapses (reduced by 6 +/- 2 %). 4. Blockers of Q-, L- or T-type Ca2+ channels had no significant effects on peak synaptic conductance at either type of synapse. 5. We conclude that the two functionally distinct types of preganglionic terminal in sympathetic ganglia which synapse on the same neurone differ in their expression of particular types of voltage-dependent Ca2+ channels. Both types utilize N-type channels and channels resistant to blockade by specific antagonists, but Ca2+ entry through P-type channels makes a substantial contribution to acetylcholine release only at weak synapses.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Elspeth McLachlan.