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Biomedical subjects

M Fitzgerald

Publications and source records attributed to M Fitzgerald.

At least 91 records · Page 5Linked to original sources
PubMed1984

Alterations in the structure, function, and chemistry of C fibers following local application of vinblastine to the sciatic nerve of the rat.

Vinblastine, a transport blocker, was applied locally to the sciatic nerve in rats. It was found to be a powerful neurotoxin with a dose-dependent action, destroying all afferents at doses of 5 X 10(-4)M, primarily C fibers at intermediate doses of 2.5 X 10(-4)M, and only at a critically low dose of 10(-4)M was a degeneration-free axon transport blockade, lasting for 4 to 5 days, produced. Such transport block failed to alter thermal responsiveness of the rats as measured behaviorally, by the flexor reflex, or by dorsal horn cell responses. It did, however, significantly reduce both the chemical sensitivity of the C afferents and their ability to produce neurogenic edema. This began 24 hr after treatment and lasted 4 to 5 days. Therefore, it is likely that these functions are dependent on the continuous transport of some compound to the axon terminals from the cell body. This low concentration of local vinblastine treatment also resulted in depletion of fluoride-resistant acid phosphatase from C fiber terminals in the dorsal horn of the spinal cord. Transmission from C fibers to second-order neurons in the spinal cord, however, was totally unaffected. Substance P levels in the spinal terminals was largely unaffected, although in 1 of 5 cases there was depletion. It appears, therefore, that some, but not all, retrograde changes in sensory neurons following peripheral nerve damage can be mimicked by blockade of axon transport. The effects following vinblastine treatment are compared to other peripheral nerve manipulations, such as cut, crush, and application of local capsaicin.

Afferent Pathways↗
PubMed1983

The termination pattern of sciatic nerve afferents in the substantia gelatinosa of neonatal rats.

A study was carried out to determine at what stage of development the adult pattern of primary afferent projections to the substantia gelatinosa (SG) is first established. Horseradish peroxidase conjugated wheat-germ agglutinin (WGA-HRP) was applied to cut ends of sciatic nerves at mid-thigh level in adult and neonatal rats aged 1-16 days. The distribution of transganglionically transported label in primary afferent terminals in SG was reconstructed from transverse sections of spinal cord segments L1 to S1. The distinctive U-shaped projection field of the sciatic nerve in SG of the adult was found to exist in miniature form already in the second postnatal day 24 h after WGA-HRP had been applied. The highly specific somatotopic projections of primary afferents to SG are probably established before birth. Any delay in the maturation of functional specificity in the dorsal horn of the neonate cannot be attributed to the absence or disorganization of anatomical projections to SG of primary afferent inputs.

Afferent Pathways↗
PubMed1983

The properties of neurones recorded in the superficial dorsal horn of the rat spinal cord.

The physiological properties of neurones in the superficial laminae of the dorsal horn of the fourth and fifth lumbar segments of the rat spinal cord have been investigated in decerebrate spinal animals. Both extracellular recordings with platinum-plated tungsten microelectrodes (n = 72) and intracellular recordings with glass microelectrodes (N = 79) were made. Attempts were made to fill cells intracellularly with horseradish peroxidase or Lucifer Yellow. Thirty-seven percent of the intracellularly injected neurones were recovered after histological processing and their cell bodies found to be in lamina 1 or 2 and in the dorsal white matter overlying lamina 1. The dendritic spread of the stained neurones was maximal in the rostrocaudal plane with a restricted mediolateral spread. The physiological properties of the extracellularly recorded units, the intracellularly unidentified units, and the intracellularly stained units were the same. The neurones were characterized by low background activity and all had excitatory receptive fields on the lower limb. Some neurones responded only to low-threshold mechanical stimulation of the skin or only to noxious skin stimulation but the majority of units (58%) were wide-dynamic-range cells responding to both types of stimuli. Receptive field classification was made questionable, however, by the existence of cells (9%) that exhibited a spontaneous shift in the size of their receptive fields and in the type of stimulus that elicited a response. The neurones in the superficial dorsal horn commonly showed a marked inhibition to repeated cutaneous stimuli (27%) or a prolonged afterdischarge followed a single stimulus (20%). Afferent input from the sural nerve was found to be from A and C fibres in both extra-and intracellular recordings. A delta- and C-mediated excitations were most common although convergent inputs from A beta-fibres occurred in 40% of units. No correlation was found between cell structure or distribution of dendritic fields and physiological properties in our small sample of intracellularly stained cells. The morphology of the cells was highly diverse, as were the different receptive fields. There was, however, some correlation between the location of cell bodies and their responses. Neurones responding only to low-threshold stimuli were distributed either in the dorsal white matter or in inner lamina 2. Wide-dynamic-range cells were distributed throughout the superficial dorsal horn. These results suggest that neurones of different shapes and positions may subserve the same function and, conversely, that neurones of the same shape and position may subserve different functions.

Animals↗
PubMed1983

Influences of contralateral nerve and skin stimulation on neurones in the substantia gelatinosa of the rat spinal cord.

Stimulation of high threshold A delta and C fibre peripheral afferents inhibits dorsal horn cells on the other side of the spinal cord. The substantia gelatinosa (SG) is an area full of interneurones known to have commissural connections across the spinal cord. The role of SG in this contralateral inhibitory pathway is investigated here. Forty-three SG cells were recorded in the lumbar dorsal horn of decerebrate spinal rats. Their ipsilateral excitatory receptive fields and responses to sciatic nerve stimulation were recorded. Repetitive electrical stimulation was then applied to the contralateral sciatic nerve. Eight (19%) units were excited by such stimulation. A brief tetanus was followed by an increase of ongoing activity lasting 30 s to 10 min. These cells did not, however, have excitatory contralateral fields. A small separate group of 4 cells (9%) were mildly inhibited by heating or pinching the contralateral limb. The significance of contralateral excitation of some SG cells is discussed in the light of the predominantly inhibitory contralateral effect on dorsal horn cells in laminae 4 and 5. It is suggested that some SG cells may be inhibitory interneurones in their effect on deeper cells.

Afferent Pathways↗
PubMed1983

Cognitive and physiologic responses to EMG biofeedback and three types of pseudofeedback during a muscular relaxation task.

Four groups of normal human subjects were tested for their ability to reduce frontal muscle tension levels during presentation of veridical auditory biofeedback or auditory pseudofeedback. A double-blind methodology was used. Three groups of subjects assigned to the pseudofeedback conditions received a feedback signal that was not contingent on EMG activity but that followed one of three different patterns. One group received a truly random signal, the second received a signal that gradually increased in frequency (apparent failure), and the third received a signal that gradually decreased in frequency (apparent success). Dependent measures included both physiologic (frontal and neck EMG) and subjective reactions to the relaxation task. The different patterns of pseudofeedback did produce reliably different subjective responses, suggesting that the manipulations succeeded in producing unequal nonspecific effects that were unrelated to the feedback contingency specifically. However, these differential subjective effects were not strongly reflected in the physiologic responses since the differences in EMG levels among the four groups did not differ significantly at any stage of training. An analysis of the integrity of the double-blind procedure showed that although experimenters were effectively kept blind to group assignment, subjects' responding suggested a response bias as well as the possibility that the double-blind was breached. The utility of the double-blind methodology in biofeedback experiments is discussed and suggestions for future research are offered.

Biofeedback, Psychology↗
PubMed1982

Alterations in the ipsi- and contralateral afferent inputs of dorsal horn cells produced by capsaicin treatment of one sciatic nerve in the rat.

Dorsal horn cells in the lumbar spinal cord of decerebrate spinal rats were examined 7-21 days following local application of capsaicin to the sciatic nerve. Such local capsaicin treatment is known not to influence the size of the incoming A and C fibre afferent volley. The receptive field properties and primary afferent input of cells on both sides of the cord, that is ipsi and contralateral to the treated nerve, were examined. On the treated side, the percentage of cells excited by C fibres from the capsaicin treated nerve was 30% of normal and the number of cells responding to noxious heating of the cutaneous receptive field was reduced by 50%. A fibre input and low and high threshold mechanical input were normal. The receptive field size was larger in many cells innervated by the treated nerve. On the side opposite to the treated nerve, responses to noxious and non-noxious stimulation of the untreated limb were unaffected as was the input from the untreated sciatic nerve. Receptive fields were somewhat larger than normal. Effects were also observed from contralateral stimuli. Cells on both sides of the cord were found with excitatory contralateral receptive fields and excitatory responses to trains of high intensity stimulation to the contralateral sciatic nerve. In untreated animals the effect of such contralateral stimulation is inhibitory. The results show that peripheral nerve capsaicin treatment causes long lasting reduction of the C fibre input to dorsal horn cells on the treated side. However, it also results in changes in the inhibitory and excitatory receptive fields of cells on both sides of the cord.

Afferent Pathways↗
PubMed1982

Chronic blockade of sciatic nerve transmission by tetrodotoxin does not produce central changes in the dorsal horn of the spinal cord of the rat.

Rat sciatic nerves were treated with tetrodotoxin (TTX) for 4--10 days, by implanting a glass capillary tube filled with TTX into the nerve through the epineurium. Following this treatment the somatotopic organization of receptive fields in the L4 dorsal horn, an area of cord normally responding only to foot stimulation. The map was normal in animals treated with TTX. Dorsal horn levels of fluoride-resistant acid phosphatase, substance P, somatostatin, cholecystokinin-like peptide, neurotensin and neurophysin were also normal as assessed from density of staining. These results are discussed in the light of the positive changes that are seen following chronic sciatic nerve section.

Acid Phosphatase↗
PubMed1982

Do opioid peptides mediate a presynaptic control of C-fibre transmission in the rat spinal cord?

A presynaptic inhibitory role for opioid peptides in the control of C-fibre-evoked activity in the dorsal horn has been investigated. The excitability of C-fibre terminals in the dorsal horn of decerebrate spinal rats was tested using intraspinal terminal stimulation and recording the size of the antidromic C wave from the dorsal roots. Naloxone (1-2 mg/kg) failed to alter the baseline terminal excitability of the C-fibres, but reduced the increase in terminal excitability produced by A-fibre afferent conditioning stimuli. The inhibition of postsynaptic C-evoked activity in lamina 5 cells produced by A-afferent fibre conditioning stimuli was also reduced by naloxone. This effect may reflect the reversal of an opioid-mediated presynaptic inhibition, although blockade of a direct postsynaptic inhibitory action could also be involved.

Animals↗
PubMed1982

If substance P fails to fulfil the criteria as a neurotransmitter in somatosensory afferents, what might be its function?

In the first part of this paper, a series of examples are described where substance P content of afferent C fibres and responses which have been attributed to C fibre excitation vary independently. Thirteen sets of data fail to support the proposal that SP is an excitatory transmitter for noxious inputs. In the second part an alternative hypothesis is proposed in which C fibres would have functions in addition to impulse propagation. It is shown that C fibres are involved in establishing and maintaining the connection between afferent fibres and central cells and that transport mechanisms play a role in this connectivity control. Therefore it is proposed that the chemicals in C fibres should be examined for their possible action on regulatory mechanisms as well as for neurotransmitter action.

Action Potentials↗
PubMed1982

The time course and specificity of the changes in the behavioural and dorsal horn cell responses to noxious stimuli following peripheral nerve capsaicin treatment in the rat.

Capsaicin, a neurotoxin which acts specifically on sensory primary afferent C-fibres was applied locally to one sciatic nerve of a group of rats. One to sixteen days following this a series of behavioural and electrophysiological studies were performed. The latency of foot withdrawal of the rats to a controlled thermal noxious stimuli was significantly elevated (200%). The peak increase occurred on day 1 after treatment; the response then fell to a steady but elevated level for up to 16 days. Responses to noxious mechanical stimuli were unaffected by capsaicin treatment. Single unit analysis of the dorsal horn of the spinal cord showed that the number of neurones in deep laminae (4, 5 and 6) responding to a C peripheral volley was normal (60%) for the first 2 days after treatment. On day 3 post treatment, the number of cells with a C input began to fall reaching a maximal decrease on day 7 (25%), where it remained up to day 16. In contrast to this delayed effect on C-evoked responses, the number of cells responding to noxious heating of the skin fell from control levels of 60% down to 20% on day 1 and remained decreased for up to 16 days. The onset of thermal analgesia following local, capsaicin treatment, therefore, closely parallels the time course of the decrease of noxious heat-evoked responses in the dorsal horn. Since at early pretreatment times, the electrically C-evoked activity is normal these effects are likely to be due to action on peripheral C-fibre nociceptors in the skin. At a later stage capsaicin also appears to act on the central terminals of fibres reducing transmission to second order dorsal horn neurones.

Animals↗
PubMed1981

Lamina-specific alteration of C-fibre evoked activity by morphine in the dorsal horn of the rat spinal cord.

The effect of systemic morphine (5 mg/kg) on the C-fibre evoked activity in the dorsal horn of decerebrate spinalized rats has been investigated. Activity in units recorded from lamina 5 was inhibited in a naloxone-reversible fashion by morphine. However, morphine produced variable changes in the C-evoked activity of units recorded within the substantia gelatinosa, some units showing excitation, some inhibition and some an alteration in the timing and pattern of the C-evoked activity.

Afferent Pathways↗
PubMed1981

The sequence 5'-AAUAAA-3'forms parts of the recognition site for polyadenylation of late SV40 mRNAs.

We have observed three effects of deletion mutations on polyadenylation of late SV40 mRNAs. The first class of mutants lack segments (-3 to -14 bp) between the 5-AAUAAA-3' and normal poly(A) site. These mutants produce mRNas polyadenylated at new sites, downstream from the wild-type site. The poly(A) site is moved farther downstream as the deletions become larger; as a result, polyadenylation always occurs within an 11-19 nucleotide range from the AAUAAA sequence. The second class of mutants lack segments (-12 to -30 bp) between the AAUAAA sequence and the coding region of the mRNA. The poly(A) site for only one of these mutants was studied (dl1457, -12 bp). In this case, the spatial relationship between AAUAAA and poly(A) site is altered. dl1457 produces a class of mRNAs polyadenylated at the first Ca following the AAUAAA sequence, as well as other mRNAs polyadenylated farther downstream. Finally, a 16 bp deletion that includes the AAUAAA sequence prevents poly(A) addition.

Animals↗
PubMed1980

Haemodynamic effects of increasing extracellular potassium concentration in ACTH-induced hypertension in sheep.

1. ACTH administration (20 microgram day-1 kg-1) to sheep produces hypertension associated with a raised cardiac output and hypokalaemia. 2. The aim of the present experiments was to detail the haemodynamic changes associated with restoration of the extracellular potassium concentration in sheep with ACTH-induced hypertension. 3. After 7 days of ACTH treatment potassium chloride (10 mmol/h) was infused for 3 days to restore plasma [K+] to the pre-ACTH value. 4. ACTH reduced plasma [K+] from 4.4 +/- 0.1 to 3.2 +/- 0.2 mmol/l but 3 days of potassium chloride infusion returned plasma [K+] to 4.3 +/- 0.2 mmol/l. 5. ACTH increased mean arterial pressure from 67 +/- 2 to 88 +/- 1 mmHg in the first 7 days and it remained elevated during potassium chloride infusion (91 +/- 5 mmHg on day 10). 6. Cardiac output rose with 7 days ACTH treatment from 4.9 +/- 0.2 to 6.0 +/- 0.6 l/min but fell progressively with potassium chloride infusion to 4.9 +/- 0.3 l/min on day 10. 7. These studies suggest that potassium status or extracellular [K+] may play a role in determining the haemodynamic profile associated with steroid-induced hypertension.

Adrenocorticotropic Hormone↗