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P D Wall

Publications and source records attributed to P D Wall.

At least 19 recordsLinked to original sources
PubMed1992

Long-range afferents in the rat spinal cord. II. Arborizations that penetrate grey matter.

1. The caudal extent of the collateral arborizations of entering sensory fibres in rat spinal cord was investigated by two methods: bulk labelling of peripheral nerves by injection of horseradish peroxidase conjugated to cholera toxin (B-HRP) and by antidromic stimulation using small currents from microelectrodes in the spinal cord while recording from single units in peripheral nerve or dorsal root. 2. The results show that injection of B-HRP into the sural or sciatic nerve labelled sural afferents in the grey matter three to four segments caudal to their root entry and sciatic nerve fibres were located in S4, the most caudal segment examined, four to six segments caudal to their root entry. 3. Detailed mapping with microelectrode stimulation showed that the parent descending fibres from filaments dissected from the L1 dorsal root coursed more than 20 mm, seven to eight segments caudal to the entry point in the dorsal columns and sent branches into the grey matter. Single units from the sural nerve were also followed caudally into the S2 and S3 spinal cord segments and also issued collateral branches into the grey matter. 4. The present results suggest that there is close agreement in the caudal penetration of long-ranging afferents by using complementary anatomical and electrophysiological methods.

Afferent Pathways↗
PubMed1992

Repair and regeneration: experimental aspects of spinal cord disease.

Regeneration of spinal cord neurons after injury depends on first, the presence of trophic factor(s) which prevent death, induce growth and maintain the viability of the neurone and second, the regenerating neurites must overcome glial scars, extracellular matrices and white matter barriers to reinnervate their target. Attempts at promoting regeneration by using grafts of prosthetic material, Schwann cells and neural tissue have largely been unsuccessful. Although growth could be induced, penetration of regenerating neurites through damaged areas of the spinal cord has been limited. There is as yet very little beneficial functional recovery.

Animals↗
PubMed1991

Long-range afferents in the rat spinal cord. 1. Numbers, distances and conduction velocities.

The caudal extent of the penetration of primary afferent axons from the T12 and L1 dorsal roots and sural nerve has been investigated in adult decerebrate spinal rats. Microelectrode stimulation at the root entry zone (REZ) and at further caudal points in the spinal cord was used to generate antidromic action potentials in single fibres recorded in dorsal roots or peripheral nerves. A total of 209 units were recorded in T12 and L1 dorsal roots and 27% of these could be antidromically activated 10 mm caudal to the REZ. Fifteen percent of the units could be stimulated at the L4-5 border, 15 mm caudal to the T12 segment whereas 4.5% of the axons could be stimulated 25 mm caudally in the S4 segment, 11 segments caudal to the entry segment. Similar recordings made from units in the sural nerve showed that of all the sural axons that penetrated to the L6 segment 50%, 18% and 2% of these reached the S1, S2 and S4 segments respectively. The conduction velocities of these units were clearly in the A-beta range when recorded in the nerve but decreased on entering the spinal cord and were reduced by 83% at their caudal end point. The results show that substantial numbers of primary afferents have long-ranging caudal branches in areas beyond the regions of known postsynaptic effects. The functions of these caudal projections are unclear but they may represent a potential substrate for the development of functional connections under conditions of disease or denervation.

Afferent Pathways↗
PubMed1991

Neuropathic pain and injured nerve: central mechanisms.

A satisfactory explanation of neuropathic pain must include mechanisms capable of generating three types of pain: ongoing, episodic and allodynic. It must explain why many such pains develop very soon after injury while others occur after long delays. It must take into account the many painless neuropathies and the unpredictable relationship of the pain to the pathology in the painful neuropathies. While these diseases clearly start in the periphery and peripheral changes must contribute to the pain, there are also three types of central change. First changes in the afferent impulse barrage can induce long term shifts of central synaptic excitability. Second, changes of the chemical substances transported from the periphery to the cord produce alterations of cord cell excitability. Third, central control mechanisms can change into a pathological state permitting hyperexcitability. The combined peripheral and central pathology offers more than explanation since each factor could be a target for prevention as well as cure.

Central Nervous System↗
PubMed1990

Effects of lesions in the anterolateral columns and dorsolateral funiculi on self-mutilation behavior in rats.

The possible role of the anterolateral columns (ALCs) and dorsolateral funiculi (DLF) in pain mechanisms was examined from the effects of lesions in these tracts (alone or combined) on tests for chronic deafferentation pain (autotomy) in rats. Spinal lesions alone (i.e., without denervation) in either ALC or DLF or combined DLF-ALC did not lead to any form of self-mutilation behavior. Cervical surgery, without spinal lesion, followed by limb denervation (sham) resulted in similar autotomy characteristics to those observed following limb denervation alone (control). Both results were considered as one set of controls. ALC lesions simultaneous with, or 1-2 weeks prior to limb denervation (ipsilaterally or contralaterally) produced significant delay in onset of autotomy and decrease in percentage of rats showing this behavior. DLF lesions followed by limb denervation produced significant acceleration of onset of autotomy and increase in percentage of rats showing this behavior. Combined DLF-ALC lesions with limb denervation produced intermediate effects between those observed following either ALC or DLF lesions alone. These results give further support to the concept that autotomy is related to rostral transmission of nociceptive information and that a spino-bulbo-spinal inhibitory loop involving the DLF and ALC is triggered by chronic deafferentation pain.

Animals↗
PubMed1990

Cross-excitation in dorsal root ganglia of nerve-injured and intact rats.

1. Experiments based on teased fiber recording from rat sciatic nerve have shown that a small proportion of primary afferent neurons in intact dorsal root ganglia (DRGs) fire spontaneously. The prevalence of this discharge is substantially increased if the sciatic nerve has been chronically injured. 2. We now show that in most cases this ongoing DRG activity can be augmented by tetanic stimulation of the axons of neighboring neurons, where the active neuron itself has not been stimulated. In addition, some previously silent DRG neurons can be cross-excited by neighbors. This novel form of neuron-to-neuron communication is termed "DRG crossed afterdischarge." Cross-excitation never occurred at fixed latency in response to single stimulus pulses and is therefore not a case of ephaptic cross talk. 3. Crossed afterdischarge occurred only if the spontaneously active neuron and the stimulated neighbors shared the same DRG. It occurred in 83.5% of the spontaneously active neurons sampled that had myelinated (A) axons, but in only 4.4% of spontaneously active neurons with unmyelinated (C) axons. Among initially silent neurons, stimulation of neighbors evoked firing in 3.1% of A-fibers but in no C-fibers. 4. Crossed afterdischarge responses began within 500 ms of stimulation onset (with the use of 50-Hz tetani) and increased in magnitude for about the first 30 s of stimulation, declining thereafter. Intense excitations were often followed by a short period of depression until the original rate of ongoing discharge was restored. 5. The magnitude of crossed afterdischarge responses increased with increasing stimulation frequency until saturation. Minimal responses occurred with the use of tetani of as little as 1 Hz. Maximal responses occurred with the use of 100-200 Hz tetani. 6. The inclusion of C-fibers in the afferent volley produced little if any augmentation of responses. 7. Cross-excitation was demonstrated in DRGs in which many or all peripheral afferent axons were intact and continued to innervate hind limb skin. In these preparations natural cutaneous stimulation was shown to be capable of evoking crossed afterdischarge responses. The most effective stimuli were gentle or firm rubbing of the foot. Noxious pinch, heat, cold, and chemical stimulation was ineffective. 8. DRG crossed afterdischarge is a mechanism whereby sensation in response to peripheral stimulation may be distorted in time, space, and modality. Because its prevalence is much increased after axotomy, it might contribute to neuropathic sensory abnormalities, including pain, in patients with nerve injury.

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

Direct spinal effect of a benzodiazepine (midazolam) on spasticity in man.

The water-soluble benzodiazepine, midazolam, was administered epidurally over the lumbar enlargement 18 times to 9 patients with spasticity due to severe spinal cord injury. Doses of 1.25-3.75 mg produced a rapid decrease of spasticity which lasted 1 h. After the maximal reduction of spasticity, the patients became drowsy. While the results suggest a direct action of midazolam on the spinal cord to reduce spasticity, the effect does not contribute to its usefulness as a therapeutic tool.

Adult↗
PubMed1988

Slow changes in the flexion reflex of the rat following arthritis or tenotomy.

(1) The flexor reflex was measured in control decerebrate spinal rats by recording the motor axon activity in the nerve to biceps femoris evoked by a pressure stimulus to the hindpaw. A brief (1 Hz, 20 s) conditioning stimulus to peripheral nerves with sufficient strength to activate C fibres results in a prolonged increase in this flexor reflex. If the conditioning stimulus is applied to a cutaneous nerve, the sural, the facilitation lasts 5 (5.0 +/- 1.6, n = 28) min. However, if the same conditioning stimulus is applied to the muscle nerve to gastrocnemius, the facilitation lasts up to an hour (54.0 +/- 8.3 min, n = 16). (2) Ankle joint urate arthritis was induced by the injection of 1.25 mg sodium urate crystals into one ankle joint. Two hours after the injection, conditioning of the flexor reflex by brief stimulation of the sural or gastrocnemius nerves produced the same effect as in control animals. However, 24 h after the injection, sural nerve conditioning produced the same effect on the flexor reflex as in controls but gastrocnemius nerve conditioning produced only 8 min (8.3 +/- 1.6, n = 8) of facilitation instead of the expected 54 min. (3) The decreased ability of the muscle nerve to produce prolonged facilitation was not dependent on a saturation of the flexor reflex since the reflex could still be enhanced briefly by the conditioning stimuli. It was also not dependent on a continuous input from the arthritic ankle since the decrease is still apparent when the ankle has been denervated 24 h after the beginning of the arthritis.(ABSTRACT TRUNCATED AT 250 WORDS)

Achilles Tendon↗
PubMed1988

Ankle joint urate arthritis in rats provides a useful tool for the evaluation of analgesic and anti-arthritic agents.

Arthritis was induced in ether anesthetised rats by injecting 1.25 mg of sodium urate crystals into the ankle joint. Twenty-four hr after the injection the ankle is swollen and the animal does not place full weight on the affected foot. The ankle is more sensitive than normal to movement and pressure. Responses to stimulation of the foot and toes on the arthritic limb are reduced due to a reluctance to move the affected limb. These measures, which reflect ongoing pain, hyperalgesia or tenderness and guarding, are attenuated in animals treated with dexamethasone, phenylbutazone, and morphine, as well as in animals whose nerves to the ankle had been pretreated with capsaicin. Guanethidine and colchicine failed to influence the behavioural responses to the urate injection. Ankle joint urate arthritis has advantages over other models of arthritis for therapeutic testing in that in a short time it affects a single joint in rats, and it produces responses which can be assessed by simple, sensitive measures.

Analgesics↗
PubMed1988

Effects of lesions to rat spinal cord lamina I cell projection pathways on reactions to acute and chronic noxious stimuli.

(1) Lamina I contains large numbers of nociceptive specific cells and wide-dynamic-range (WDR) cells which respond to both noxious and innocuous stimuli. Many of the cells project to the brain. 82% of the projecting axons travel by way of the contralateral dorsolateral funiculus (DLF). (2) Section of the contralateral DLF produced no change in behavioural response to brief mechanical or thermal or chemical stimuli. However, section of the contralateral DLF greatly accelerated the slow onset autotomy in response to section of the sciatic and saphenous nerves. (3) Section of the ipsilateral DLF or bilateral section produce the same acceleration of onset of autotomy as is produced by contralateral DLF section. Section of dorsal columns does not change the long-term onset of autotomy. (4) Destruction of cells with ibotenic acid in the contralateral parabrachial area where many lamina I cells are known to terminate produced the same acceleration of autotomy as was observed after DLF lesions. Contralateral cortical lesions were without effect on autotomy. (5) It is proposed that the lamina I projection system is more concerned with long-latency long-duration reactions to prolonged events than to abrupt reactions to brief stimuli. The behavioural results reported here are consistent with McMahon and Wall's physiological hypothesis that a contralateral DLF projecting pathway excites cells in the parabrachial area which in turn excite descending control systems running mainly in the ipsilateral DLF to affect spinal dorsal horn cells.

Animals↗
PubMed1988

Descending excitation and inhibition of spinal cord lamina I projection neurons.

1. Lamina I cells were recorded in the lumbar dorsal horn of decerebrate rats. Their projecting axons were mainly located in the contralateral dorsolateral funiculus (DLF) in the upper cervical cord. 2. The effect on these cells of short and long trains of stimuli applied to the upper cervical DLF was examined by measuring the ongoing activity of the cells, their response to peripheral stimuli, and the size of their receptive fields. 3. The presence of tonic descending influences from brain stem to spinal cord was investigated by measuring the properties of the lamina I cells before and during block of descending impulses. 4. The results of DLF stimulation and of cord block show that substantial and prolonged excitation affected many cells, whereas some were inhibited for shorter periods of time. 5. The experiments were repeated with stimulation of the DLF caudal to chronic section to eliminate descending fibers. The results suggest that the changes of excitability in intact animals were partly produced by stimulation of descending fibers and partly by the invasion of collaterals activated by the antidromic stimulation of the axons projecting from the lamina I cells. 6. Although long trains of DLF stimuli generally excited lamina I cells, only inhibitions were seen in the deep dorsal horn. Moreover, stimulation rostral to an acute unilateral DLF lesion was without effect on lamina I cells but inhibited deep cells. 7. It is proposed that the lamina I cells might activate brain stem circuits, which in turn influence deep dorsal horn cells.

Action Potentials↗
PubMed1988

Recruitment of ineffective synapses after injury.

This paper describes three ways in which cells may expand their receptive fields with no concurrent change of morphology. (a) The subliminal fringe. Classical physiology described the presence of excitatory inputs that were not sufficiently strong to raise the cells above its firing threshold unless there was a decrease of inhibition or a summation of excitatory inputs. (b) Receptive-field expansion triggered by the arrival of impulses but sustained by central mechanisms. (c) Receptive-field expansion following a change in the transport of substances into the region of synapses.

Animals↗