Influence of changes of tooth temperature on reflex and central activity evoked by stimulation of tooth pulp afferents.

The importance of the temperature of the dentine was studied in teeth prepared for electrical stimulation. During experiments with the mouth open, the temperature of teeth covered by cement was normal. The digastric EMG and the brainstem--evoked response following electrical stimulation of the tooth pulp as well as the threshold for eliciting a jaw-opening response remained constant throughout prolonged experiments. However, heat produced by the cement used to fixate the tooth electrodes could have damaged the tooth if the dentine temperature had exceeded 45 degrees C. A careful preparation of the tooth pulp by repeated application of thin layers of cement allowed an adequate preparation without damage to tooth pulp afferents.

Convergence of afferents from superior sagittal sinus and tooth pulp on cells in the upper cervical spinal cord of the cat.

Units in the dorsolateral area of the upper cervical cord respond to craniovascular stimulation. This study examined tooth pulp responses in this area in cats. Eleven of 21 units tested in the dorsolateral area had convergent inputs from superior sagittal sinus and tooth pulp; while 10 units had sagittal sinus, but not tooth pulp, input. Mean response latency to tooth pulp stimulation (25.8 ms) was significantly longer than to superior sagittal sinus stimulation (9.8 ms). Half of the units had cutaneous receptive fields; and in five units, action potentials could be evoked by electrical stimulation in the posterior complex of the thalamus.

Craniovascular nociceptive pathways relay in the upper cervical spinal cord in the cat.

Units in the dorsolateral area of the upper cervical cord and the ventroposteromedial nucleus of the thalamus respond to stimulation of cranial vessels. To study the physiological role of the upper cervical cord in craniovascular transmission, we used a cryoprobe to interrupt reversibly neural transmission through the cord while recording in the thalamus. Twenty-one of 47 thalamic units tested showed reversible diminution in their response to superior sagittal sinus stimulation during cervical cord cooling. In contrast, receptive field responses and spontaneous thalamic activity were unaffected. These data suggest offt the cervical cord relays craniovascular nociceptive afferents.

Pain threshold changes following acupuncture, measured with cutaneous argon laser and electrical tooth pulp stimulation, a comparative study.

1. The present study compared the argon laser technique for pain threshold measurements with the previously often used threshold measurements with electrical tooth pulp (TP) stimulation. 2. Conditioning stimuli with acupuncture was given since it previously has been shown to induce pain threshold changes. Acupuncture needles were inserted in the hands and arms and electrically stimulated. 3. The experiments were performed in a single blind fashion comparing pain threshold effects after either acupuncture or placebo. Pain threshold measurements with a method of limits were used with both electrical TP and the argon laser method. 4. In comparison to placebo the pain thresholds increased after acupuncture, both on the face and on the hand, with the argon laser method, while the TP thresholds were not influenced. No significant pain threshold change was detected with either the argon laser or the TP method following placebo treatment. 5. The results indicate that the argon laser used for sensory testing with a method of limits is a useful method for pain threshold measurements. The difference in pain threshold effects induced by acupuncture measured with the argon laser and the TP stimulation, are discussed and related to mechanisms that may differ between the two types of pain threshold measurements.

Pain threshold measurements with cutaneous argon laser, comparing a forced choice and a method of limits.

1. With the argon laser technique cutaneous nociceptors can be activated with high specificity and reproducibility making it a useful tool in psychophysical pain studies. This study was designed to examine and compare two different psychophysical methods combined with the argon laser technique. 2. Pain thresholds on different locations of the body and on different skin types were measured with (i) the method of limits and (ii) the forced choice method. 3. A significant correlation between the pain thresholds measured with the two different methods was detected on feet and hands. The method of limits yielded significantly higher pain thresholds in glabrous skin than hairy skin. Higher pain thresholds were also detected on the right side of the body. No statistically significant difference between sexes was found. A high reproducibility over time as well as in-between investigators was found for the method of limits. 4. Its concluded that the argon laser for pain threshold measurement with the method of limits is useful and preferred to the forced choice, since the method of limits is easier to perform and also less time consuming.

Transplanted children's experiences of daily living: children's narratives about their lives following transplantation.

Transplantation is often an appropriate choice of treatment for children with end-stage renal, liver, heart or lung disease. Over the last decade, mortality and morbidity figures have been relatively stable and quality of life fairly good in children who have undergone organ transplantation. Few studies however, have focused on the experiences of transplantation from the child's perspective. The child's view is an important factor when evaluating the 'true' outcome and quality of life after transplantation. The aim of the present study was to illuminate the meaning of transplanted children's experiences of daily living. Unstructured interviews were carried out with 18 children and adolescents, aged 4-18 yr, who had undergone organ transplantation. Their narratives were transcribed and interpreted using a phenomenologic-hermeneutic method inspired by the philosophy of Ricoeur. Two main themes emerged: Being satisfied with life, with the themes: being able to live a normal life; someone who cares; coping with one's new life; and being dissatisfied with life, with the themes: not being able to live a normal life; lacking someone who cares; not being respected; existential thoughts. Most of the children and adolescents were of the opinion that they lived a normal life while the rest strived to achieve a normal life. Social support and mental support were of great importance and, when lacking, had negative consequences. Multi-disciplinary co-operation between healthcare professionals and between the healthcare system, the school and the family is crucial in order to optimize the outcome and quality of life after organ transplantation in children.

Recordings of polymodal single c-fiber nociceptive afferents following mechanical and argon-laser heat stimulation of human skin.

Recordings were made in the peroneal nerve of healthy volunteer subjects from C-mechano-heat (CMH) nociceptors (n=25) with their receptive fields in the skin on the dorsum of the foot. The investigation focused on afferent single C-fiber activity induced by short (200 ms) high-intensity argon-laser light pulses projected to localized spots of the skin. Cutaneous heat stimulation with the argon laser, 2-3 times the activation threshold, induced inter-burst spike frequencies in the nerve, reaching 50 Hz, while mechanical stimulation 10-20 times threshold only evoked frequencies reaching 10 Hz. The decrease in conduction velocity of action potentials in the C-fiber afferents following mechanical and heat stimulation was closely related to the degree of activation. Following a laser pulse of 200 ms, a spike pattern with highly reproducible inter-spike intervals was evoked with a fast saturation. On the contrary, a high variability in the number of action potentials evoked by both heat and mechanical stimuli was found, depending on the location of stimuli within the receptive field. A relation between the conduction velocity and the peak firing within the spike train following laser stimulation was detected. Heat and mechanical stimulation activated single C-fibers in matching spots within the same skin areas, in line with the assumption that the two modalities in the CMH-fibers share matching morphological cutaneous substrates. No correlation was found in thresholds or excitability to mechanical and heat stimulation, respectively. This suggests that subsets of receptors exist within nerve endings of the cutaneous receptive fields, with the ability to generate action potentials independent of heat and mechanical stimuli. Unexpectedly, no signs of sensitization or other inflammatory responses were observed after repeated laser pulses; on the contrary, a rapidly developing fatigue was observed when single spots were repeatedly stimulated. However, no fatigue was observed if neighboring spots were stimulated, indicating a localized generator of the fatigue. In each subject, a good correlation was observed between the reported pain sensation and the activity evoked in the afferent C-fibers by the laser. However, the magnitude of the reported pain sensation to comparable degrees of C-fiber activation showed a high variability between different subjects. A fairly good subjective estimate of the afferent-fiber activation was observed when skin spots from 3- down to 1-mm diameter were stimulated. In a few individuals, no painful sensation was reported when the stimulated spots were reduced to 1-mm diameter, despite the occurrence of multiple spikes in single C-fiber afferents, amplifying the importance of spatial summation in the perception of pain.

Recordings of human polymodal single C-fiber afferents following mechanical and argon-laser heat stimulation of inflamed skin.

Activity in single C-fiber afferents, whose cutaneous receptive fields were on the dorsal side of the foot (n=10), were recorded in the peroneal nerve of healthy voluntary subjects. Characterization of the fibers with respect to thresholds and field areas were made before and after cutaneous inflammation, which was induced with mustard oil. To test the nociceptive heat modality, a high-intensity argon laser was used and single 200-ms light pulses were focused onto the skin. The mechanical properties were tested with von Frey-type filaments. In the uninflamed skin, heat and mechanical stimulation activated single C-fibers in matching skin areas. The areas were all within the receptive field borders defined by electrical cutaneous stimulation. The mustard-oil-induced cutaneous inflammation was subjectively reported by the subjects as being moderately painful. In six of the units, a spontaneous activity was induced in the sample of ten previously non-active units. Before the inflammation, the 200-ms argon-laser pulse evoked a highly reproducible pattern of spike-trains. Following inflammation, this pattern was reproducible, but appeared with a significantly reduced activation rate despite the same energy being delivered to the skin both before and after the inflammation. A reduction in slope of the stimulus-response relationship was also observed after inflammation. Following inflammation, changes occurred with expansion both of the mechanical- and heat-receptive fields. The expansion was delineated by the areas defined by electrical stimulation. Following inflammation, the threshold to heat was decreased, but that to mechanical stimuli was not. No relation was detected between the threshold change and the degree of receptive-field expansion. The subjective pain reported changed following inflammation with an increase in the perceived pain in relation to the recorded action potentials, which emphasizes the importance of either an increase in sensitivity in the central nervous system or an increase in peripheral spatial summation after inflammation.

Antispastic effects of L-dopa.

Antispastic effects of the noradrenaline and dopamine precursor l-3,4-dihydroxyphelanine (L-dopa) were investigated in 11 subjects in which exaggerated stretch reflexes developed after spinal cord injuries. The effects were evaluated from changes in the electromyographic (EMG) response of the quadriceps muscle during tendon jerks evoked by standardized taps over the patellar tendon, in clonus and in resistance to passive movements of the limb. After administration of L-dopa, EMG responses occurring 30-150 ms after the tendon tap decreased to about 50% of control, and clinical tests revealed a marked decrease in the resistance to muscle stretches and in the degree of clonus. The effects were maximal within about 1 h. The depressive actions of L-dopa are interpreted as being exerted primarily at the spinal level, since they were evoked in paraplegics and tetraplegics. The results support the previous hypothesis that group II muscle afferents contribute to.the exaggerated stretch reflex in spastic patients because L-dopa depresses transmission from group II but not from group I muscle afferents. They also indicate the possibility of using L-dopa in the treatment of spastic patients.

Localized responses in the midsuprasylvian gyrus of the cat following stimulation of the central lateral nucleus in thalamus.

Evoked responses were mapped in the cerebral cortex following low intensity electrical stimulation in serial penetrations of the medial and intralaminar nuclei of the thalamus of the cat. A projection was found from one of the intralaminar nuclei, the central lateral nucleus (CL) to the midsuprasylvian gyrus, mainly areas 5 and 7. The projection is suggested to be direct, since the evoked responses had a short latency initial positivity. The most characteristic type of response consisted of this early positivity followed by two successive negativities. The earlier, so called first negativity followed high frequency stimulation and was recorded in a smaller area of the cortex than the later, so called second negativity. The first negativity is suggested to depend on monosynaptic depolarization and activation of cortical cells. The second negativity failed at frequencies higher than 10 Hz and was strongly depressed by the administration of barbiturates; it is suggested to depend on polysynaptic depolarization and cellular activity. In electrode penetrations of the cortex both negativities reversed at the border between cortical layers II and III, indicating a superficial termination of thalamic afferents in the cortex. The cortical evoked response to CL stimulation was facilitated by light mechanical and low intensity electrical stimulation of the periphery, as well as by electrical stimulation of the tooth pulp. The possible significance and function of this projection is discussed in relation to arousal, attention and pain.

Projection of tooth pulp afferents to the thalamus of the cat. I. Focal potentials and thalamocortical connections.

Electrical stimulation of tooth pulp afferents in cats evoked short latency focal potentials in the basal ventromedial nucleus of thalamus (VMB), in the border zone between this nucleus and the arcuate nucleus of the ventrobasal complex (VBA), and in the marginal zone of VBA and the external nucleus of the ventrobasal complex (VBX). No responses were found in the centre of VBA and VBX. Very few responses were found in the intralaminar region. The projection from the tooth pulps was bilateral, but the best responses following stimulation of the ipsi- and the contralateral tooth pulps could be evoked at slightly different locations within VMB. The mean latency of the responses was shorter following stimulation of the contralateral tooth pulp than following stimulation of the ipsilateral one. Electrical stimulation in VMB, VBA, and VBX evoked focal potentials in thalamocortical projection fibres, which were recorded from in the white matter below areas SI and SII after decortication by suction. Conditioning stimulation of the tooth pulps suppressed these responses within 200 ms if the stimulating electrode was placed at the border between VBA and VMB, suggesting that tooth pulp stimulation activates a thalamocortical projection with a postexcitatory inhibition. Finally, lesions were made in the thalamus and their effects were checked on the cortical responses to tooth pulp stimulation. If the lesion included the region of VMB bordering to VBA the cortical responses decreased in amplitude. It is concluded that VMB and the borderzone between VMB and VBA are important relays between the nociceptors of the tooth pulp and the sensory cortex.

Field potential analysis of the cortical projection of the central lateral nucleus in the cat.

A previous field potential study has indicated a monosynaptic projection of fibres from the central lateral nucleus (CL) to the mid-suprasylvian gyrus (MSSG). The present study, which is based on an analysis of current source density (CSD), aims to investigate further the sites of major localized synaptic activities in different layers of the MSSG after electrical stimulation in the CL. An initial positive surface potential was evoked in the MSSG with a latency of 3-5 ms and followed by a large negative potential with a peak latency of 8-15 ms. The initial positivity was only found in the rostral part of the MSSG, which corresponds to area 5. The positivity reversed in deeper layers. The CSD analysis showed a sink at a depth from 650 to 1050 microns. A corresponding source was found more superficially at 400-600 microns. This indicates that CL fibres have an excitatory synaptic termination on the soma or proximal dendrites of neurons in layers III and IV. The surface negative potential reversed at the border between layers II and III, suggesting a superficial CL projection. The CSD analysis of potentials in superficial layers showed a sink appearing between the pial surface and a depth of 350 microns, and a source lying in layers below. This indicates a depolarization of apical dendrites of cells in layers II and III. The superficial sink appeared in a large part of the MSSG. Application of a solution of 0.5% gamma-aminobutyric acid (GABA) on the surface of the cortex blocked the superficial sink and source and revealed a prominent sink current in layers III and IV in agreement with a deep termination of CL fibres. Application of a solution of 25 mM DL-2-amino-5-phosphono-valeric acid (APV) abolished CL-evoked cortical responses indicating that N-methyl-D-aspartate (NMDA) receptors are involved in the cortical activation. The CSD analysis confirms that CL has a wide superficial projection to the MSSG. It also confirms a deeper monosynaptic projection from CL to area 5.

Sympathetic and noradrenaline effects on C-fibre transmission: single-unit analysis.

Single afferent unmyelinated fibres were dissected from the otherwise intact sural nerve in anesthetized rabbits. The sympathetic trunk could be stimulated via electrodes implanted through the abdomen. The response in single C fibres was elicited by electrical stimulation in the cutaneous innervation area of the fibre. Sympathetic stimulation (8 Hz, 1 ms pulses, 5 mA for 60 s) increased the latency in all tested C fibres (2.0% +/- 0.8%, mean +/- SD, n = 17). In 48% of the units the amplitude of the action potential decreased (26.4% +/- 12.3%) during sympathetic stimulation. Infusion of noradrenaline (5 micrograms min-1) increased (7.7% +/- 4.1%) the latency in all units and increased (36.9% +/- 29.8%) the amplitude of 25% of the units. The effects of sympathetic stimulation and noradrenaline infusion were blocked by pre-treatment with phentolamine (3 mg kg-1 i.v.). The results suggest that catecholamines change the membrane properties of unmyelinated fibres.

Thalamic nociceptive mechanisms in cats, influenced by central conditioning stimuli.

Field potentials and single cell activity evoked by tooth pulp (TP) stimulation were studied in the ventrobasal (VB) complex of the cat. The experiments were performed using a conditioning-test paradigm. Evoked cell activity or field potentials following TP stimulation was used as a test. Conditioning stimulus was given to different regions of the thalamic central lateral nucleus (CL). Conditioning electrical stimulation in medial (ML 2.8-3.6 mm) parts of CL induced a depression of the TP evoked response in 10 cells. Stimulation sites in lateral CL (ML 3.6-4.2 mm) induced facilitation in eight cells and decreased activity in seven cells. Tooth pulp evoked field potentials in thalamus were facilitated by a preceding stimulation in lateral CL. Cells in the lateral parts of CL are suggested to induce an increased activity in cells in the VB complex which mediate nociceptive information. This effect is suggested to be mediated via a CL induced disinhibition at a reticular thalamic (RE) or at a VB complex level. The medial parts of CL seem to give a traditional feedback inhibition on VB cells. Such an effect is also suggested to be mediated via the RE complex. The importance of these findings are discussed with relation to changes in the thalamus that may occur following long lasting nociceptive stimulation.

Projection from the thalamic intralaminar nuclei on the isocortex of the rat: a surface potential study.

Cortical surface potentials evoked from thalamic intralaminar nuclei have been studied in rats anaesthetized with chloralose. Stimulation with low current intensity in central lateral nucleus (CL), evoked potentials in large areas of the rat isocortex. In the posterior parietal cortex responses with a short latency negativity were evoked which followed high frequency repetitive stimulation. Its latency and ability to follow high frequency stimulation indicated a monosynaptic connection from CL to this part of the cortex. The short latency potential was followed by a second negativity with longer latency and varying amplitude. This second negativity did not follow repetitive stimulation exceeding 10 Hz, and was also reduced by supplementary doses of anaesthetics, indicating a polysynaptic origin. Stimulation at different CL sites elicited cortical potentials with short latency in a topographical pattern. Laminar analysis in the parietal and motor cortex suggested both a superficial and a deep layer termination of afferents from CL. Similar topografical relations and afferent layer distributions have previously been found in cats. The role of the thalamocortical projection from CL to parietal cortex in arousal, attention and pain mechanisms is discussed.

Dorsal column inhibition of nociceptive thalamic cells mediated by gamma-aminobutyric acid mechanisms in the cat.

Cells in posterior parts of the cat thalamus were investigated. Responses in single units excited by electrical stimulation in the lateral funiculus (LF), the dorsal column nucleus (DCN) or the canine tooth pulp (TP) were analysed. All cells had a spontaneous resting activity which could be increased by extracellular iontophoretic application of DL-homocysteic acid (DLH) and decreased by gamma-aminobutyric acid (GABA). No effect on the spontaneous firing rate was observed following iontophoresis of the selective GABA-antagonists, picrotoxin (GABA-A receptor antagonist) or saclofen (GABA-B receptor antagonist). However, the decreased firing following GABA application was partially blocked by picrotoxin but not by saclofen. A phasic inhibition induced by DCN stimulation in nociceptive thalamic cells is indicated since simultaneous administration of picrotoxin increased the evoked response. This type of inhibitory mechanism could not be detected following LF or TP stimulation. The extracellular activity evoked by electrical stimulation of LF or TP was significantly depressed by preceding electrical stimulation in the DCN. This inhibition was reversed by simultaneous administration of picrotoxin, indicating an involvement of GABA-A receptors. The reversal of the DCN-induced depression of the late responses following LF stimulation occurred after application of saclofen. It is suggested that this effect is partly mediated via GABA-B receptors. Results from the present study indicate an interaction in the thalamus between presumed low-threshold (DCN) and presumed nociceptive afferents (LF and TP) similar to that previously described in the spinal cord.

Properties of single neurons in the cat midsuprasylvian gyrus.

Responses of cells in the midsuprasylvian gyrus (MSSG) of cats were investigated following electrical stimulation of the central lateral nucleus (CL) of the thalamus and tooth pulp, low-threshold cutaneous or visual afferents. Electrical stimulation in CL induced excitation in many cells located in cortical areas 5 and 7. Cells in these areas also received input from somato-sensory and visual afferents. Cells in MSSG showed a wide convergence from tooth pulp, low-threshold cutaneous afferents and from the CL. The majority of wide convergent cells in area 5 were found in layers IV and V, while cells excited by CL and tooth pulp were found in layers II and III. Similarities were found between CL and tooth pulp evoked responses with regard to the excitation-inhibition pattern. The excitation evoked from CL and tooth pulp was less often followed by a hyperpolarizing potential compared to that seen after low-threshold lip, paw and visual afferent stimulation. Stimulation sites in the lateral parts of CL-evoked responses with the shortest latencies in area 5. In this part of the cortex, short latency synaptic potentials were found in cells in superficial layers. In the same area, synaptic potentials of short latency were also evoked by electrical stimulation of tooth pulp, lip and paw. Light-flash stimulation evoked responses with the shortest latencies in area 7. The results of this study demonstrate that putative nociceptive information reaches the parietal association cortex and that part of this input may be relayed via CL. We suggest that the excitatory influences of nociceptive and CL stimulation is related to behavioral arousal and attention mechanisms.

Effects of naloxone on dental pain threshold following muscle exercise and low frequency transcutaneous nerve stimulation: a comparative study in man.

Previous studies have shown that muscle exercise and low frequency transcutaneous nerve stimulation (TNS) give rise to an analgesic effect in humans and animals. Endorphin has been proposed to mediate this analgesia. In this investigation, the effect of muscle exercise and low frequency TNS, on dental pain thresholds was studied and the possible involvement of endorphinergic mechanisms was investigated using naloxone as an antagonist. Dental pain thresholds were measured in 11 volunteers following leg or arm exercise and after low frequency TNS of the hands or face. After exercise (20 min) or stimulation (30 min) either 0.8 mg naloxone (2 ml) or saline (2 ml) was injected i.v. in a double-blind fashion. Pain thresholds were measured repetitively before and after exercise or stimulation. Both leg and arm exercise increased pain threshold. Stimulation of the hands also increased pain threshold, but less than arm exercise. A marked increase in pain threshold was seen after face stimulation. These changes in pain threshold were unaffected following injections of either naloxone or saline, except for an early and short-lasting reduction when naloxone was injected following arm exercise. The increases in pain threshold following muscle exercise and after low frequency TNS, showed similarities suggesting that a common mechanism might be involved. The pain threshold increase after arm exercise could only be partially mediated by endorphinergic mechanisms.