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Biomedical subjects

P P Robinson

Publications and source records attributed to P P Robinson.

At least 19 recordsLinked to original sources
PubMed2007

Na(v)1.7 sodium channel expression in human lingual nerve neuromas.

OBJECTIVE: Peripheral branches of the trigeminal nerve are often damaged during the removal of lower third molar teeth, and a small proportion of patients who sustain an injury develop persistent chronic pain. The cause of the pain is not clear and there are no satisfactory methods of treatment. The aim of the present study was to examine the expression of the sodium channel subtype Na(v)1.7 in damaged human lingual nerves, and to identify any association between Na(v)1.7 expression and reported symptoms of dysaesthesia. METHODS: Eleven neuromas-in-continuity (NICs) and 11 nerve-end neuromas (NENs) were studied, and were all obtained at the time of surgical repair of the damaged lingual nerve. Specimens were categorised as being obtained from patients with symptoms or without symptoms, according to the degree of pain, tingling or discomfort that had been experienced. The tissue was prepared and processed for indirect immunofluorescence, and image analysis was used to quantify the percentage area of PGP 9.5-labelled tissue that also contained Na(v)1.7. RESULTS: The results demonstrated that sodium channel Na(v)1.7 was expressed in human lingual nerve neuromas. There was no direct relationship between the level of expression of Na(v)1.7 and the patients' symptoms of dysaesthesia. However, in NICs there was found to be an inverse correlation between Na(v)1.7 and macrophage expression, and in symptomatic NICs a direct correlation was found between Na(v)1.7 expression and axonal apposition. CONCLUSIONS: These data suggest that Na(v)1.7 expression alone does not play a primary role in initiating the painful symptoms of dysaesthesia. The development of neuropathic pain may involve complex interactions including changes in ultrastructure and ion channel density.

Axons↗
PubMed2006

Effects of capsaicin and menthol on oral thermal sensory thresholds.

OBJECTIVE: To determine the long-term effect of capsaicin and short-term effect of menthol on oral thermal thresholds. DESIGN: The thresholds for cold detection (CDT), warm detection (WDT), cold pain (CPT) and warm pain (WPT) were determined in 11 regular chilli-eaters (capsaicin group) and 11 control subjects that were closely matched for age, gender and ethnicity. The effect of menthol was determined by asking all 22 participants to suck a lozenge containing 0.52% menthol for 5min. RESULTS: An ANOVA revealed a significant difference between the capsaicin and control groups (P=0.014), with the greatest difference in the WDT (capsaicin group 4.7+/-2.7[S.D.] degrees C; control group 2.3+/-2.2 degrees C). Immediately after sucking a menthol lozenge there was a significant rise in the CDT (2.2+/-1.1 degrees C to 5.9+/-6.2 degrees C; P<0.01) and WDT (3.6+/-2.7 degrees C to 7.6+/-4.4 degrees C; P<0.001). CONCLUSIONS: The consumption of foods containing capsaicin and menthol significantly alters thermal sensory thresholds in the oral cavity. Dietary habits should therefore be taken into account when intra-oral thermal thresholds are determined.

Adult↗
PubMed2003

Neuropeptide expression following ligation of the ferret lingual nerve.

Previous studies on the ferret inferior alveolar nerve found a close association between the spontaneous neural activity generated at a site of nerve injury, and the accumulation of neuropeptides in the injured axons. More recent electrophysiological studies on the lingual nerve revealed high levels of spontaneous activity 3 days after injury, a decline at 3 weeks and a late rise at 3 months. In the present study we have used immunocytochemical techniques to see whether this time course of spontaneous activity is again paralleled by an accumulation of neuropeptides. In 20 anaesthetised adult ferrets the left lingual nerve was ligated and sectioned distally, and the animals left to recover for 3 days, 3 weeks or 3 months. The tissue was processed using indirect immunofluorescence and image analysis was used to quantify levels of the neuropeptides; calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal polypeptide (VIP), galanin (GAL), enkephalin (ENK) and neuropeptide Y (NPY). Immunoreactivity to all of the neuropeptides was present proximal to the ligature 3 days after injury, and these high levels of expression had decreased considerably by 3 weeks. By 3 months ENK and NPY expression had almost disappeared proximal to the ligature, but levels of CGRP, SP, VIP and GAL had increased slightly. This was also accompanied by an accumulation of all of the neuropeptides, except NPY, in the portion of nerve immediately distal to the ligature. This late accumulation of certain neuropeptides coincides with the increase in spontaneous activity seen in our previous electrophysiological studies and supports the suggestion that neuropeptides may play a role in the aetiology of sensory disorders after nerve injury.

Animals↗
PubMed2003

Nerve damage and third molar removal.

The surgical removal of lower third molars endangers both the lingual and inferior alveolar nerves. Patients sustaining an injury to either of these nerves must be managed correctly, and this requires a diagnosis of the injury type and regular monitoring of the recovery of sensation. Surgical intervention for a damaged inferior alveolar nerve is not usually indicated but may be undertaken: if the nerve is completely divided and the severed ends are misaligned; if a bony fragment has compressed the mandibular canal; or if the patient suffers from persistent neuropathic pain. In contrast, after injury to the lingual nerve, if sensory testing demonstrates no neural recovery within 3-4 months, exploration of the injury site and microsurgical repair of the damaged nerve is indicated.

Cranial Nerve Injuries↗
PubMed2001

Calcitonin gene-related peptide modifies the ectopic discharge from damaged nerve fibres in the ferret.

Previous studies in our laboratory have shown that the neuropeptide, calcitonin gene-related peptide (CGRP) accumulates at a site of inferior alveolar nerve injury at the time when high levels of spontaneous activity and mechanical sensitivity are recorded electrophysiologically. The present study was undertaken to determine whether or not the CGRP could be playing a role in initiating or modulating the neuronal activity. In 18 anaesthetised adult ferrets the left inferior alveolar nerve was sectioned and ligated and recovery permitted for 3 days. Under a second anaesthetic recordings were made from a fine nerve filament, containing up to four active or silent units, dissected from the nerve proximal to the injury. After recording activity for a 30 min control period, CGRP and then the CGRP antagonist (CGRP 8-37) were applied either by close-arterial injection or topically (10(-4) M, 0.2 ml). After each application activity was recorded for a 30 min period. Recordings were made from 52 units, of which 26 (50%) were spontaneously active and 30 (58%) were mechanically sensitive. The spontaneous activity in five units was increased by the application of CGRP, and the CGRP antagonist subsequently reduced the activity in two of these units. Activity was induced by CGRP in three previously silent units. Overall, activity was affected in 19% of the units studied. We conclude that CGRP present within a neuroma may initiate or modulate the level of ectopic discharge from some damaged nerve fibres and therefore may contribute to the sensory disturbances which follow nerve injury.

Action Potentials↗
PubMed2001

Neuropeptide expression in the ferret trigeminal ganglion following ligation of the inferior alveolar nerve.

Previous studies have found changes in neuropeptide expression in trigeminal ganglion cells after inferior alveolar nerve (IAN) section. These changes may play a part in the persistent sensory abnormalities that can be experienced after trigeminal nerve injuries. Here, neuropeptide expression after IAN ligation was studied, as this type of injury is thought to be more likely to result in sensory disturbances. The neuropeptides investigated were substance P, calcitonin gene-related peptide, enkephalin (ENK), galanin (GAL), neuropeptide Y (NPY) and vasoactive intestinal polypeptide. In anaesthetised adult female ferrets the left IAN was sectioned and the central stump tightly ligated. Recovery was allowed for 3 days, 3 or 12 weeks before perfusion-fixation. In a second procedure, 1 week before perfusion, the IAN was exposed and an injection made central to the injury site, using a mixture of 4% Fluorogold and 4% Isolectin B4 conjugated to horseradish peroxidase, to identify cell bodies with axons in the inferior alveolar nerve and cells with unmyelinated axons within this population, respectively. Control experiments involved tracer injection alone. After harvesting the tissue, sagittal sections were taken from both the right and left ganglia and immunohistochemical staining used to reveal the presence of peptides and Isolectin B4 tracer. The results showed a significant decrease in GAL expression after injury and an increase in ENK and NPY expression. No significant differences were seen in the expression of the other peptides or in the proportion of lectin-positive cells at any time after injury. When compared with previous data, significant differences were found between peptide expression following nerve ligation and nerve section. These results reveal that the changes in neuropeptide expression in the trigeminal ganglion that follow IAN injury are dependent upon the type of injury. The extent to which changes in the central neuropeptide levels contribute to the development of sensory disorders remains to be established.

Analysis of Variance↗
PubMed2001

Changes in neuropeptide expression in the trigeminal ganglion following inferior alveolar nerve section in the ferret.

Changes in neuropeptide expression in afferent nerve fibres may play a role in the persistent sensory abnormalities that can be experienced following trigeminal nerve injuries. We have therefore studied changes in the expression of the neuropeptides substance P, calcitonin gene-related peptide, enkephalin, galanin, neuropeptide Y and vasoactive intestinal polypeptide in the trigeminal ganglion following peripheral nerve injury. In anaesthetised adult female ferrets, the left inferior alveolar nerve was sectioned and recovery allowed for three days, three weeks or 12 weeks prior to perfusion-fixation. During a second procedure, one week prior to perfusion, the inferior alveolar nerve was exposed and an injection made central to the injury site using a mixture of 4 % Fluorogold and 4 % isolectin B4 conjugated to horseradish peroxidase to identify cell bodies with axons in the inferior alveolar nerve and cells with unmyelinated axons within this population, respectively. Control animals received tracer injection alone. After harvesting the tissue, sagittal sections were taken from both the right and left ganglia and immunohistochemical staining was used to reveal the presence of peptides and isolectin B4-horseradish peroxidase tracer. Within the Fluorogold-labelled population, cell counts revealed a significant reduction in the proportion of substance P-containing cells at three days (P = 0.0025), three weeks (P = 0.0094) and three months (P = 0.0149) after nerve section, and a significant reduction in the proportion of calcitonin gene-related peptide-containing cells at three days (P = 0.0003) and three weeks (P = 0.007). No significant changes were seen in the expression of the other peptides, or at other time periods. A significant reduction in the number of isolectin B4-horseradish peroxidase-positive cells (with unmyelinated axons) was seen at three days (P = 0.0025), three weeks (P = 0.0074) and three months after the injury (P = 0.0133). These results demonstrate a significant reduction in the expression of some neuropeptides in the early stages after inferior alveolar nerve section. Some of the results differ markedly from those reported previously in other systems, and may be related to the specific nerve studied, species variations or differences between spinal and trigeminal nerves.

Afferent Pathways↗
PubMed2001

Nerve injury-induced pain in the trigeminal system.

This article reviews some recent findings on peripheral mechanisms related to the development of oro-facial pain after trigeminal nerve injury. Chronic injury-induced oro-facial pain is not in itself a life-threatening condition, but patients suffering from this disorder undoubtedly have a reduced quality of life. The vast majority of the work on pain mechanisms has been carried out in spinal nerve systems. Those studies have provided great insight into mechanisms of neuropathic spinal pain, and much of the data from them is obviously relevant to studies of trigeminal pain. However, it is now clear that the pathophysiology of the trigeminal nerve (a cranial nerve) is in many ways different to that found in spinal nerves. Whereas some of the changes seen in animal models of trigeminal nerve injury mimic those occurring after spinal nerve injury (e.g., the development of spontaneous activity from the damaged axons), others are different, such as the time-course of the spontaneous activity, some of the neuropeptide changes in the trigeminal ganglion, and the lack of sprouting of sympathetic terminals in the ganglion. Recent findings provide new insights that help our understanding of the etiology of chronic injury-induced oro-facial pain. Future investigations will hopefully explain how data gained from these studies relate to clinical pain experience in man and should enable the rapid development of new therapeutic regimes.

Animals↗
PubMed2000

Ectopic neural activity from myelinated afferent fibres in the lingual nerve of the ferret following three types of injury.

Sensory disturbances following nerve injury may result from abnormal neural activity initiated at the injury site. We have studied the activity generated in the lingual nerve after three types of injury which may have variable potentials for the initiation of sensory disturbances. We have also compared the results with those found after damage to the inferior alveolar nerve, another branch of the trigeminal nerve, to determine whether differences in nerve fibre type or location affect the level of abnormal activity. In anaesthetised adult male ferrets the left lingual nerve was either ligated and cut distally, chronically constricted, or sectioned and allowed to regenerate. Following recovery periods of 3 days-6 months, single unit electrophysiological recordings were made from central to the injury site. After all three types of injury, some of the damaged axons at the injury site developed spontaneous activity (up to 36% of units) and mechanical sensitivity (up to 35% of units). There were significantly fewer spontaneously active units after ligation than after the other two types of injury but the level of mechanical sensitivity was not significantly different between the three types of injury. There was a significant increase in the spontaneous activity between 3 weeks and later recovery periods following both ligation and section injuries, and this late increase was not seen in our previous studies on the inferior alveolar nerve. Differences in the time-course of ectopic activity in adjacent branches of the trigeminal nerve suggest that the fibre types or anatomical relationships affect the outcome of injury.

Afferent Pathways↗
PubMed2000

A prospective, quantitative study on the clinical outcome of lingual nerve repair.

We previously showed in laboratory studies that the most effective method for repair of damaged lingual nerves was by excision of the neuroma, mobilization of the stumps, and direct reapposition with epineurial sutures. We have now undertaken a prospective study in a series of 53 patients treated by this method and have evaluated the outcome by quantifying and comparing the results of tests of sensation before and after operation. The outcome in individual patients was variable. However, pooled data from all patients showed a highly significant improvement in sensation at the final assessment 12 months or more after the repair. The proportion of patients who responded to most or all light touch stimuli increased from 0% to 51% after repair, and the proportion who responded to pin-prick stimuli increased from 34% to 77%. There was no correlation between the final results of any of the tests and the delay before repair. None of the patients regained completely normal sensation and there was no reduction in the number with spontaneous paraesthesia or pain. However, fewer patients tended to bite the tongue by accident and most of them considered the operation worthwhile. These data show that lingual nerve repair is effective in most patients and we suggest that it should be offered to all those who show few signs of spontaneous recovery after injury.

Adolescent↗
PubMed1999

Sympathetic nerve sprouting fails to occur in the trigeminal ganglion after peripheral nerve injury in the rat.

Peripheral nerve injury induces sprouting of sympathetic nerve fibers in dorsal root ganglia after spinal nerve injury. In the present study, we sought to determine the extent of intraganglionic noradrenergic sprouting in the trigeminal system. The inferior alveolar nerve, a major branch of the mandibular division, or the infraorbital nerve of the maxillary division was either ligated or chronically constricted in Sprague-Dawley rats and recovery permitted for either 2-3 or 6-9 weeks. In some animals both nerves were injured. Using immunohistochemistry with tyrosine hydroxylase antibodies, we found no signs of sympathetic nerve fiber sprouting in the trigeminal ganglion after injury. In contrast, sciatic nerve injury in rat littermates induced a widespread autonomic nerve outgrowth in affected DRGs. Thus, sensory ganglion sympathetic nerve sprouting does not seem to be a general outcome of PNS injury, but is restricted to certain specific locations. Sympathetic nerve fiber networks that surround primary sensory neurons have been suggested to form a structural basis for interactions between the sympathetic and sensory nervous systems after PNS injury. Such interactions, sometimes resulting in paraesthesia or dysaesthesia in patients, appear to be less common in territories innervated by the trigeminal nerve than in spinal nerve regions. The lack of injury-induced intraganglionic sympathetic sprouting in the trigeminal ganglion may help to explain this observation.

Animals↗
PubMed1999

The effect of surgical technique on lingual nerve damage during lower 3rd molar removal by dental students.

We have previously shown that avoidance of lingual flap retraction with a Howarth periosteal elevator during lower 3rd molar removal, reduces the incidence of lingual nerve damage. In that study, the surgery was undertaken by qualified staff and we have now assessed the effect of revising the method taught to our junior undergraduate dental students. We evaluated the outcome of surgery undertaken by 2 consecutive years of students, each group being taught 1 of the 2 methods. A total of 200 patients requiring lower 3rd molar removal under local anaesthesia were included in the study. In year 1, the surgery included elevation of a lingual flap and insertion of a Howarth elevator adjacent to the lingual plate; in year 2 this part of the procedure was avoided by using a purely buccal approach. There were no significant differences between the levels of tooth eruption and types of impaction of the teeth removed in each year. Lingual sensory disturbance occurred in 3 patients in the 'flap' group (3.3%) and in 1 patient (0.9%) in the 'no flap' group. As this incidence is not significantly different in the 2 groups (P < 0.4), we conclude that avoidance of lingual retraction by students undertaking lower 3rd molar removal does not appear to place the lingual nerve at greater risk. In view of the results of our previous study, we therefore advocate this method for use in undergraduate dental education.

Clinical Competence↗
PubMed1998

Neuropeptide immunoreactivity in ligature-induced neuromas of the inferior alveolar nerve in the ferret.

Injury to branches of the trigeminal nerve can sometimes result in persistent dysaesthesia. In an attempt to understand the aetiology of this condition we are currently investigating changes which occur at the injury site. In the present study we have examined the expression of seven neuropeptides, all of which have been implicated in nociceptive transmission, or have previously been shown to have altered expression following nerve injury. In 20 adult ferrets the inferior alveolar nerve was sectioned and ligated, and recovery permitted for 3 days, 8 days, 3 weeks, 6 weeks or 12 weeks. Longitudinal sections of the neuromas were processed using immunohistochemical techniques to quantify the expression of substance P, calcitonin gene-related peptide, vasoactive intestinal polypeptide, galanin, somatostatin, enkephalin and neuropeptide Y. After 3 days, all of the neuropeptides were expressed at the injury site. In the neuromas examined after longer recovery periods these levels of expression had declined and were similar to those found in the contralateral controls. This initial high level, followed by a decline, parallels the incidence of ectopic neural activity recorded electrophysiologically in the same model. It is, therefore, possible that the accumulation of neuropeptides at the injury site may play a role in the initiation or modulation of ectopic neural activity.

Animals↗
PubMed1998

Sympathectomy does not affect the early ectopic discharge from myelinated fibres in ferret inferior alveolar nerve neuromas.

Ectopic neural activity from damaged axons is thought to contribute to the development of sensory disorders following nerve injury. Here we have studied the role of sympathetic fibres in the generation or potentiation of this abnormal activity by determining the effect of predegenerating these fibres. Twelve adult ferrets were used in the study and six of them underwent sympathectomy by removal of the left superior cervical ganglion. Electrophysiological recordings were made from myelinated axons in fine filaments dissected from the inferior alveolar nerve, 3 days after it had been ligated further distally, and the level of spontaneous activity and mechanical sensitivity was determined. There was no significant difference between the level or characteristics of spontaneous activity, or the level of mechanical sensitivity, in the two groups of animals. We conclude that, in this animal model, the absence of sympathetic nerve fibres does not affect the development or characteristics of ectopic neural activity in the early period following nerve injury.

Animals↗
PubMed1998

The effect of surgical medicaments on peripheral nerve function.

Surgical medicaments are often placed in close proximity to peripheral nerves and may be responsible for some postoperative sensory disturbances. In this study we investigated the effect of four medicaments -- BIPP, (bismuth iodoform paraffin paste), Whitehead's varnish (compound iodoform paint), Surgicel (oxidized regenerated cellulose) and Carnoy's solution (ethanol, chloroform and acetic acid) -- on peripheral nerve function. The experiments were carried out on the saphenous nerve in anaesthetized adult rats. Electrical stimuli (30 V, 0.1 ms duration) were applied to the saphenous nerve through electrodes placed distally (at the ankle) to evoke a compound action potential (CAP) which was recorded proximally (in the thigh). The CAP was recorded before, and for 2 h after, the application of the medicament to a 1 cm length of nerve between the electrodes. In other animals (n = 4 in each group) recordings were made after the medicament had been placed in a connective tissue pocket immediately overlying the nerve for a 2-week period. BIPP (n = 4) had no immediate or delayed effect on neural function, whereas Whitehead's varnish (n = 4) and Carnoy's (n = 4) solution both blocked neural conduction within 2 min of being placed adjacent to the nerve. The effect of Surgicel (n = 8) was more variable; axonal conduction was blocked within 2 h in five of the eight experiments undertaken. After the application of Whitehead's varnish or Surgicel for 2 weeks, the CAPs had regained characteristics which were similar to those of the controls, but after the application of Carnoy's solution they remained significantly diminished (P < 0.004). These results suggest that, with the exception of BIPP, the medicaments tested could be responsible for some postoperative sensory disturbances, and the effects of Carnoy's solution on neural function may be persistent.

Acetic Acid↗
PubMed1998

Afferent activity from myelinated inferior alveolar nerve fibers in ferrets after constriction or section and regeneration.

To investigate possible peripheral mechanisms for post-injury sensory disorders in the trigeminal system, we have made electrophysiological recordings from myelinated fibres in the inferior alveolar nerve (IAN) which have previously sustained an injury. In earlier experiments we have shown that axons in ligature-induced neuromas of the IAN develop spontaneous activity and mechanical sensitivity. The present study has investigated these responses after two different types of injury. In 24 anaesthetised adult male ferrets the left IAN was either chronically constricted by four loose chromic gut ligatures (12 animals) or sectioned and regeneration permitted (12 animals). After recovery periods of 3 days, 1, 3, 6, 12 or 24 weeks, single unit recordings were made from the nerve proximal to the injury site. The proportion of units which were spontaneously active ranged from 0% to 19% after constriction injury and from 0% to 10% after nerve section and regeneration. Both groups revealed a marked variability between individual animals at similar time periods. Mechanical sensitivity was found in 0-42% of units after constriction and 0-25% of units after nerve section; both groups showed a significant negative correlation between mechanical sensitivity and recovery period. None of the fibres which had regained peripheral receptive fields was either spontaneously active or mechanically sensitive. There was no significant difference between the levels of spontaneous activity or mechanical sensitivity in the two groups or that previously found in ligature-induced neuromas. Thus we conclude that widely differing types of peripheral nerve injury are capable of initiating similar raised levels of afferent activity in myelinated inferior alveolar nerve fibres.

Action Potentials↗
PubMed1996

Lingual nerve damage during lower third molar removal: a comparison of two surgical methods.

The high incidence of lingual sensory disturbance following lower third molar removal in the UK may be due to the elevation of a lingual flap and insertion of a Howarth's periosteal elevator, in an attempt to protect the lingual nerve. We have therefore studied the validity of this technique by recording the incidence of temporary and permanent lingual nerve injury during 771 operations randomly allocated to be carried out with or without lingual flap retraction. Surgery with lingual flap retraction resulted in lingual sensory disturbance in 6.9% and this persisted, requiring lingual nerve repair, in 0.8%. Surgery without lingual flap retraction resulted in lingual sensory disturbance in 0.8% (P < 0.0001) and this persisted, requiring lingual nerve repair, in 0.3%. We conclude that avoidance of lingual retraction reduces the incidence of temporary lingual nerve disturbance and does not increase the incidence of permanent damage. This indicates that use of the Howarth's in this way is invalid, and suggests that for the majority of cases, lingual retraction should be avoided.

Humans↗