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Biomedical subjects

S B McMahon

Publications and source records attributed to S B McMahon.

At least 19 recordsLinked to original sources
PubMed1992

Retrograde labelling of dorsal root ganglion cells in the rat: a quantitative and morphological comparison of Fluoro-Gold with horseradish peroxidase labelling.

We have compared retrograde labelling of rat primary sensory neurons using Fluoro-Gold (FG) and horseradish peroxide conjugated with wheat germ agglutinin (HRP-WGA). Fluoro-Gold 2.5% after 48 h transit time and FG 5% after 24 and 48 h retrogradely labelled similar numbers of cell profiles as HRP-WGA (P greater than 0.1% Student's t-test). The calculated cell size distribution for the above FG groups were similar to those for the HRP-WGA. However, FG 2.5% after a 24 h transit time labelled significantly fewer cells (P less than 0.001 Student's t-test). FG retrograde transport may be used to identify the same population of DRG cells as HRP-WGA.

Animals↗
PubMed1992

Itching for an explanation.

Itch is a distinct sensation arising from the superficial layers of skin and mucous membranes. It is elicited by histamine and probably other endogenous chemicals that excite subpopulations of unmyelinated primary afferents and spinal neurones projecting through the anterolateral quadrant to the brain. The two popular views, which propose either that itch is signalled by a labelled line system of peripheral and central itch-specific neurones or that itch is the subliminal form of pain, both fail to explain convincingly many known features. Alternative theories emphasize central processes that extract the relevant information from afferents with broad sensitivity spectra for pruritogenic and noxious stimuli. Thus, itch presents an irritating challenge for the specificity theory of somatosensation.

Animals↗
PubMed1992

Peripheral nerve injury caused by injection needles used in regional anaesthesia: influence of bevel configuration, studied in a rat model.

We have studied the immediate and long term (up to 28 days) effects of short and long bevelled needle impalement of the rat sciatic nerve. Three techniques were used to assess neural trauma and its consequences: stained longitudinal nerve sections were assessed by light microscopy and scored for injury; the extravasation of Evan's Blue dye, after antidromic electrical nerve stimulation, was used as a test of unmyelinated fibre function; the flexion withdrawal times from a noxious stimulus were measured. The results of all three experiments suggested that, should a nerve fascicle become accidentally impaled during regional anaesthesia, the lesions induced by short bevelled needles are more severe, more frequent and take longer to repair than those induced by long bevelled needles. Nerve injury induced by short bevelled needles was associated with persisting signs of injury 28 days after the injury. These results suggest that the current practice of using short bevelled needles to prevent nerve injury complicating regional anaesthesia be reassessed.

Anesthesia, Conduction↗
PubMed1992

Role of primary response genes in generating cellular responses to growth factors.

Cellular responses to growth and differentiation factors involve a complex cascade of signals that begins at the cell surface, traverses the cytoplasm, and eventually enters the nucleus. Although a great deal is known about the surface and cytoplasmic stages of this cascade, the nuclear events involved in transducing and translating growth and differentiation signals are less well understood. Recent work has implicated a set of genes known as primary response genes as critical for this process. To propagate the activation signal, these genes possess the ability not only to directly respond to upstream biochemical events, but also to transmit the signal downstream by modulating the unique changes in gene expression necessary for a particular cellular response. In this review we discuss how transcription factors encoded by primary response genes may be responsible for regulating tissue- or stimulus-specific responses associated with cellular activation.

Base Sequence↗
PubMed1991

Sprouting of peripherally regenerating primary sensory neurones in the adult central nervous system.

We have studied the ability of primary afferent neurones to proliferate within the grey matter of the dorsal horn following the degeneration of other, nearby, afferent fibres. The peripheral branches of primary afferents have the capacity to regenerate successfully over long distances, and we have examined the possibility that when they are so doing, the neurones' status changes to facilitate greatly the sprouting of afferent fibres within the dorsal horn. "Spared root" preparations (rhizotomies of L3, L4, L6, S1, and the caudal half of L5, sparing the rostral half of the L5 dorsal root) were made in adult rats. In some animals (acute preparations) the distribution of the central terminals of the spared root was assessed by labelling the sciatic nerve with WGA-HRP at the time of the rhizotomies. In other animals (chronic preparations), symmetrical bilateral spared roots were made and the sciatic nerve on one side was concomitantly crushed to trigger regrowth of the peripheral branches of these axons. Eight to 10 weeks later the sciatic nerves on both sides were labelled with HRP-WGA. In the acute preparations the reaction product was found in a limited rostrocaudal and mediolateral region of the dorsal horn. In lamina II (the lamina of densest labelling) the labelled terminals occupied an average of 1.17 +/- 0.21 mm2. In chronic preparations, the area of labelled terminals on the side of the uncrushed sciatic nerve was 1.34 +/- 0.28 mm2 (not significantly different from acute animals). However, the labelled area on the side of the crushed sciatic nerve was significantly greater, averaging 2.17 +/- 0.14 mm2.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase↗
PubMed1991

Mechanisms of sympathetic pain.

In some chronic pain states, notably causalgia and reflex sympathetic dystrophy, activity in sympathetic efferent neurones can exacerbate the pain and sympathectomies relieve it. These patients are said to have sympathetically maintained pain (SMP). In normal tissue, activity in postganglionic sympathetic efferents does not produce pain, nor is it capable of activating nociceptive sensory neurones. It can, however, induce modest firing in some mechanoreceptors. SMP is often held to result from a vicious circle of events which include changes in peripheral and central somatosensory processes, and most importantly a positive feedback element in the form of sympathetic efferent neurones which, by activating sensory neurones in the periphery, completes the vicious circle. Several specific hypotheses have been advanced as to the primary pathophysiological cause of pain in these patients. Suggestions, largely deriving from observations on animal models, include: ephaptic transmission, adrenergic receptors on sensory neurones, indirect coupling of sympathetic and sensory neurones, sensitization of nociceptive afferents, and, in the central nervous system, sensitization of dorsal horn neurones. All these suggestions have some supporting evidence, but none are able to adequately explain all the disturbances seen in patients with SMP.

Chronic Disease↗
PubMed1991

Physiological properties of primary sensory neurons appropriately and inappropriately innervating skin in the adult rat.

1. We have studied the physiology of sensory neurons innervating skin of the rat hindlimb, in three groups of animals: 1) normal animals; 2) animals in which the sural nerve (Sn) had regenerated to its original cutaneous target; and 3) animals in which the gastrocnemius muscle nerve (Gn) had previously been cut and cross anastomosed with the distal stump of the cut Sn so that its axons regenerated to a foreign target, skin. 2. Single-unit recordings were made from 222 afferents in normal, intact animals. They had conduction velocities of 0.5-53.1 m/s. The conduction velocity distribution had distinct peaks at approximately 37.5, 2.5, and 1.25 m/s, presumably corresponding to A alpha beta-, A delta-, and C-fiber populations. Eighty-two percent of the characterized myelinated fibers had low-threshold mechanosensitive receptive fields, whereas 16% were high threshold, and only 2% appeared to have no receptive field. The very large majority of low-threshold mechanosensitive receptive fields (87%) were rapidly adapting hair follicle afferents. 3. In animals with regenerated Sn, 308 afferents were recorded with conduction velocities of 0.4-58.8 m/s. However, the mean conduction velocity was lower than in control animals (P less than 0.05), and only one peak, at 27.5 m/s, was apparent for myelinated fibers. Eighty-six percent of myelinated fibers were low-threshold mechanosensitive afferents, 8.5% were high-threshold mechanoreceptors (HTMRs), and 5.5% appeared to have no receptive fields. Fewer low-threshold mechanoreceptors (LTMRs; compared with controls) were activated by hair movement (63 vs. 87%). Most of the remainder appeared to be field receptors (which were therefore more commonly observed here than in normal animals). 4. In animals in which the Gn had regenerated to skin, 430 afferents were recorded. These had conduction velocities ranging from 0.6 to 71.4 m/s, and again only one peak was apparent in the myelinated conduction velocity histogram, at approximately 17.5 m/s. Of the myelinated fibers, 79% had low-threshold mechanosensitive receptive fields in skin and 10% high-threshold mechanosensitive receptive fields. The remaining 11% apparently had no receptive field (cf. 5.5% in regenerated Sn). In contrast to normal or regrown sural afferents, only 58% of low-threshold gastrocnemius afferents in skin were rapidly adapting. Of the 42% slowly adapting afferents, many surprisingly responded to hair movement. Thus some gastrocnemius afferents seemed to have retained the adaptation properties characteristic of muscle afferents. Also surprisingly, given that the Gn contains fewer fibers than the Sn, receptive-field areas were not significantly different from regrown or normal sural fibers.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Physiological properties of primary sensory neurons appropriately and inappropriately innervating skeletal muscle in adult rats.

1. We have studied the physiology of primary sensory neurons innervating rat hindlimb muscle in the following: 1) normal control animals; 2) animals in which the gastrocnemius nerve (Gn) had regenerated to its original muscle target; and 3) animals in which the cutaneous sural nerve (Sn) had regenerated to a foreign target, muscle. 2. Single-unit recordings were made from 115 afferents in normal, intact animals. They had conduction velocities of 0.8-67.2 m/s, which were distributed with peaks at approximately 1.25, 17.5, and 47.5 m/s. Of the myelinated fibers, 88% had low-threshold mechanosensitive receptive fields and responded to ramp-and-hold stretches of the muscle. The large majority of these fibers (85%) gave slowly adapting responses to ramp-and-hold stretches or direct muscle probing. Stretch-sensitive afferents could be divided (on the basis of their responses to active muscle contraction) into in-parallel or in-series receptors (presumed muscle spindles and Golgi tendon organs, respectively). The in-parallel receptors outnumbered the in-series receptors by approximately 3:2. The 12% of fibers that were insensitive to stretches of the muscle in the physiological range could be divided into roughly equal groups of totally insensitive fibers and high-threshold fibers, which required excessive stretching of the muscle. 3. In the animals with regrown Gn, 94 single fibers with conduction velocities ranging from 11 to 60.6 m/s were studied. The myelinated conduction velocity distribution exhibited only one peak, at approximately 37.5 m/s. Only 67% of the afferents were stretch sensitive (vs. 88% in normal animals), and only about two-thirds of these (vs. 85% in normal animals) gave slowly adapting responses to ramp-and-hold stretches or muscle probing. The incidence of in-series receptors was also increased among regenerated gastrocnemius afferents. The 33% of fibers that were stretch insensitive were mostly unresponsive to even extreme forms of mechanical stimuli. This group presumably represents afferents that failed to make appropriate endings. 4. In the animals with Sn directed to muscle, 460 single afferents were recorded. Their conduction velocities ranged from 0.7 to 67.9 m/s, and the distribution exhibited only a single peak for myelinated fibers at approximately 22.5 m/s, significantly lower than for intact or regrown Gn. Only 41% of the myelinated fibers were stretch sensitive. Nearly all of these (98%) were rapidly adapting to ramp-and-hold stretches or muscle probing, in marked contrast to the other groups. Also, unlike other groups, nearly all stretch-sensitive afferents appeared to be in-series.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Methylation of an immediate-early inducible gene as a mechanism for B cell tolerance induction.

Stage-specific gene regulation is important in determining cell function during development. Immature B cells expressing membrane-bound immunoglobulin M (mIgM) are sensitive to antigen-induced tolerance, whereas mature B cells are activated by antigen. Previous studies have established an association between Egr-1 gene induction and antigen receptor (mIgM)-mediated activation of mature B cells. Here it is shown that the immature B cell line WEHI-231 and tolerance-sensitive bone marrow-derived B cells do not express Egr-1. It is further shown that lack of inducible expression in these cells is due to specific methylation of the Egr-1 gene. Thus, covalent inactivation of an activation-associated gene may explain tolerance sensitivity at specific stages of B cell development.

Animals↗
PubMed1990

A quantitative study of the central projection patterns of unmyelinated ventral root afferents in the cat.

1. The ventral roots of the spinal cord contain a large number of unmyelinated primary afferent neurones. There is some controversy, however, about the function of these fibres and the route of their central projection. Here we have used electrophysiological techniques to quantify the central projection patterns of these neurones in the segment S2 of adult chloralose-anaesthesized cats. 2. A total of 1185 single unmyelinated units were recorded in small filaments isolated from intact and de-efferented ventral roots or intact dorsal roots of the segment S2 in nineteen cats. The projection patterns of these neurones were tested using supramaximal electrical stimulation of the pelvic and pudendal nerve (the main tributaries of the spinal nerve of this segment) and of the segmental companion root (dorsal or ventral as appropriate). 3. The principal finding of this study is that 85% of unmyelinated afferent axons in the ventral root are direct and exclusive projections. They constitute a separate class of afferents which is only capable of transmitting information from the periphery via the ventral roots. However, the proportion of these fibres that enter the central nervous system is unknown and it seems likely that some of them peter out as they approach the spinal cord and end blindly. The functional role of such afferents remains obscure. 4. For the remaining 15% of unmyelinated ventral root afferents, a projection into the segmental dorsal root was found. The majority of those fibres (about two-thirds) are primary afferent neurones innervating the pia mater. Some of these units had a small spot-like receptive field and responded to mechanical stimuli such as pressure and stretch of the root. They did not have axon projections in a peripheral nerve. 5. A few (5%) unmyelinated ventral root fibres are collateral branches of normal primary afferents projecting through the dorsal root. These trifurcating neurones are a small population which make up only some 0.5% of all dorsal root ganglion cells. The functional significance of this population too is unknown. 6. For none of the fibres that projected into both dorsal and ventral root was there positive evidence for the existence of looping axons that merely make a detour into one of the roots. Although the existence of loops cannot completely be excluded, our evidence suggests that they can constitute at most 5% of the unmyelinated ventral root afferents.

Action Potentials↗
PubMed1989

Changes in spinal cord reflexes after cross-anastomosis of cutaneous and muscle nerves in the adult rat.

Evidence exists that the specification of afferent nerves and their central connections in the embryo may depend in part on influences from the peripheral target innervated. We have now investigated whether such peripheral determination persists in the adult rat using the unmyelinated afferent system of C fibres, which differ chemically in the adult depending on their target. We have previously shown that if the cutaneous sural nerve and the muscle gastrocnemius nerve are cross-anastomosed so that they grow to each other's target, the A fibres establish functional endings and the C fibres change their chemistry to that which is appropriate for the new target. Here we report that in normal adult rats, a short train of stimuli to the cutaneous sural nerve produced a brief facilitation of the flexion reflex, lasting on average only 5 min, whereas similar stimulation of the gastrocnemius-muscle nerve enhanced this reflex for an average of 54 min. In cross-anastomosed animals, stimulation of the gastrocnemius nerve (innervating skin) induced a brief potentiation of the flexion reflex, lasting on average only 3 min. By contrast, stimulation of sural nerve (innervating muscle) produced a potentiation of this reflex lasting 57 min. Thus the ability of adult afferent nerves to potentiate the flexion reflex depends on the target with which they make contact. We propose that tissue-specific factors influence some of the central actions of primary afferent neurons in the adult.

Afferent Pathways↗
PubMed1989

The response of the peripheral nerve field to controlled soft tissue expansion.

The aim of the study was to investigate the effect of controlled soft tissue expansion on the peripheral nerve field. The rat model was used with single neurone recordings at the dorsal root level related to areas of skin previously expanded over a period of 2-4 weeks. Parameters measured were: stimulation threshold, receptive field size, conduction velocity and afferent disconnection. Results indicated a sparing of neural function despite an expansion in skin area of 110%.

Afferent Pathways↗
PubMed1989

Restricted clonality of visceral sarcomas in avian sarcoma virus-infected chickens.

Experiments were undertaken to analyze proviral DNA in primary (wing web) and visceral sarcomas arising in FP chickens infected with BH-RSV(RAV-2). Using the degree of heterogeneity of BH-RSV proviral integration sites as a measure of the degree of polyclonality of sarcoma tissue, we observed that a high proportion of the visceral sarcomas examined comprised dominant clones, independently of whether these sarcomas were isolated from immune-suppressed or nonsuppressed infected chickens; by contrast, a marked heterogeneity of BH-RSV proviral integration sites was noted with primary sarcoma tissue. Several visceral sarcomas containing dominant clones were characterized by the integration of a deleted form of the BH-RSV provirus. In addition, all of the primary and visceral sarcomas exhibited sequences specific for the RAV-2 provirus, and both types of sarcoma tissue were competent for infectious sarcoma virus production.

Animals↗
PubMed1989

Quantitative analysis of peptide levels and neurogenic extravasation following regeneration of afferents to appropriate and inappropriate targets.

We have studied quantitatively the levels of substance P and calcitonin gene-related peptide in nerves innervating skin and muscle of rats, and examined the effects of cross-anastomosing these nerves so that they regenerate to an inappropriate target. We have also compared the ability of nerves to induce neurogenic extravasation with their peptide content. Peptide was measured by radioimmunoassay in the proximal section of ligated peripheral nerves, and neurogenic oedema was measured by determination of Evans Blue extravasation induced by either systemic capsaicin treatment or topical mustard oil application. The levels of these peptides are higher in cutaneous nerves than muscle nerves. This cannot be explained by differences in the number of fibres in the nerves studied. The levels of peptides fall when cutaneous afferents reinnervate muscle, and rise when muscle afferents reinnervate skin. We suggest that these changes occur because of some tissue-specific trophic influence arising from the tissue innervated. The ability to produce extravasation in skin is highly correlated with the substance P and calcitonin gene-related peptide levels of its innervation, even when this occurs in inappropriate nerves which do not normally produce extravasation.

Anastomosis, Surgical↗
PubMed1987

Peptide expression is altered when afferent nerves reinnervate inappropriate tissue.

Neuropeptides are found in specific subpopulations of primary afferent neurones. Peptide expression can be altered following axotomy or under the influence of nerve growth factor. Here we have examined the consequence of altering the peripheral target of afferent neurones. Many unmyelinated afferents from skin contain substance P-like immunoreactivity (SPLI) whilst those from muscle do not. We have found that fibres will innervate inappropriate tissue types. We have therefore cut and cross-anastomosed a skin and muscle hindlimb nerve in the rat and 10-12 weeks later analysed the regenerated nerves immunocytochemically for SPLI. Muscle afferents inappropriately reinnervating skin were found to contain many SPLI fibres in contrast to control nerves resutured to their own distal stumps. Conversely, skin afferents made to innervate muscle showed reduced levels of peptide staining. These results demonstrate the plasticity of peptide expression and suggest that factors in peripheral tissue or perhaps distal nerve sheaths exert a trophic influence on nervous system function.

Animals↗
PubMed1986

The localization of fluoride-resistant acid phosphatase (FRAP) in the pelvic nerves and sacral spinal cord of rats.

The enzyme fluoride-resistant acid phosphatase (FRAP) is present in many small diameter cutaneous but not muscle afferent nerve fibres, in the rat. Here it is shown that it is also present in many afferent nerve fibres in a visceral nerve. The depletion of the enzyme from the central terminals of fibres that are cut peripherally provides a means of mapping the main projection areas of FRAP-containing afferents within the central nervous system. It was found that pelvic afferents containing FRAP have a major projection lateral to the neck of the dorsal horn and the area of the intermediolateral cell column in spinal cord segments L6 and S1, in contrast to the main projection of cutaneous FRAP afferents whose terminations form a horizontal band in the superficial dorsal horn.

Acid Phosphatase↗