Assessment of the wind-up phenomenon in the equine nociceptive trigeminal system.

Repeated sub-threshold nociceptive electrical stimulation resulting in temporal summation of the limb nociceptive withdrawal reflex is a well-established non-invasive model to investigate the wind-up phenomenon in horses. Due to structural similarities of the trigeminal sensory nucleus to the dorsal horn of the spinal cord, temporal summation should be evoked by repeated transcutaneous electrical stimulation of trigeminal afferents. To evaluate this hypothesis repeated transcutaneous electrical stimulation was applied to the supraorbital and infraorbital nerves of 10 horses. Stimulation intensities varied between 0.5 and 1.3 times the trigemino-cervical reflex threshold defined for single stimulation. Evoked electromyographic activity of the orbicularis oculi, splenius and cleidomastoideus muscles was recorded and the signals analysed in the previously established epochs typical to the early and late component of the blink reflex and to the trigemino-cervical reflex. Behavioural reactions were evaluated with the aid of numerical rating scale. The nociceptive late component and the trigemino-cervical reflex were not elicited by sub-threshold intensity repeated transcutaneous electrical stimulation. Furthermore, the median reflex amplitude for the 10 horses showed a tendency to decline over the stimulation train so temporal summation of afferent trigeminal inputs could not be observed. Therefore, the modulation of trigeminal nociceptive processing attributable to repeated Aδ fibre stimulations seems to differ from spinal processing of similar inputs as it seems to have an inhibitory rather than facilitatory effect. Further evaluation is necessary to highlight the underlying mechanism.

Rasch-built Overall Disability Scale for patients with chemotherapy-induced peripheral neuropathy (CIPN-R-ODS).

Chemotherapy-induced peripheral neuropathy (CIPN) is a common neurological side-effect of cancer treatment and may lead to declines in patients' daily functioning and quality of life. To date, there are no modern clinimetrically well-evaluated outcome measures available to assess disability in CIPN patients. The objective of the study was to develop an interval-weighted scale to capture activity limitations and participation restrictions in CIPN patients using the Rasch methodology and to determine its validity and reliability properties. A preliminary Rasch-built Overall Disability Scale (pre-R-ODS) comprising 146 items was assessed twice (interval: 2-3 weeks; test-retest reliability) in 281 CIPN patients with a stable clinical condition. The obtained data were subjected to Rasch analyses to determine whether model expectations would be met, and if necessarily, adaptations were made to obtain proper model fit (internal validity). External validity was obtained by correlating the CIPN-R-ODS with the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) neuropathy scales and the Pain-Intensity Numeric-Rating-Scale (PI-NRS). The preliminary R-ODS did not meet Rasch model's expectations. Items displaying misfit statistics, disordered thresholds, item bias or local dependency were systematically removed. The final CIPN-R-ODS consisting of 28 items fulfilled all the model's expectations with proper validity and reliability, and was unidimensional. The final CIPN-R-ODS is a Rasch-built disease-specific, interval measure suitable to detect disability in CIPN patients and bypasses the shortcomings of classical test theory ordinal-based measures. Its use is recommended in future clinical trials in CIPN.

Nociceptive trigeminal reflexes in non-sedated horses.

Electrically induced reflexes can be used to investigate the physiology and pathophysiology of the trigeminal system in humans. Similarly, the assessment of the trigemino-cervical (TCR) and blink reflexes (BR) may provide a new diagnostic tool in horses. The aim of this study was to evoke nociceptive trigeminal reflexes and describe the electrophysiological characteristics in non-sedated horses. The infraorbital (ION) and supraorbital nerves (SON) were stimulated transcutaneously in 10 adult Warmblood horses in separate sessions using train-of-five electrical pulses. The current was increased gradually until the TCR threshold was found. The stimulus-response curve of the TCR was evaluated. At the same time as TCR, the BR response was also assessed. Surface electromyographic (EMG) responses were recorded from the orbicularis oculi, splenius and cleidomastoideus muscles. Latency, duration, amplitude of the reflexes and behavioural responses were analysed. Noxious electrical stimulation of the ION or SON evoked reflex EMG responses, with similar features regardless of the nerve that had been stimulated. Stimulations of increasing intensity elicited reflexes of increasing amplitude and decreasing latency, accompanied by stronger behavioural reactions, therefore confirming the nociceptive nature of the TCR. These findings provide a reference for the assessment of dysfunction of the equine trigeminal system.

Effect of temperature on sensory and motor conduction of the rat tail nerves.

AIMS OF THE STUDY: To assess the effect of temperature upon conduction velocity, amplitude and signal energy of the sensory and motor rat tail nerves. MATERIALS AND METHODS: Sensory and motor responses were recorded from the tail nerves in 10 adult rats at different temperatures, starting from 40 degrees C and cooling down to 16 degrees C in steps of 2 degrees C. RESULTS: The conduction velocity of the various components of the orthodromic sensory response was directly and linearly related to temperature (fastest fibres ranged from 47.7 down to 19.7 m/s), with Q(10) values of approximately 1.30, suggesting that all fibres, regardless of their diameter, were equally sensitive to changes in temperature. The motor conduction was similarly affected with a Q(10) value of 1.28 and a velocity range from 24.2 down to 9.6m/s. Amplitude and energy of the sensory responses were inversely related to temperature, reaching their maximum at 16 degrees C. Energy was by far the most temperature sensitive parameter, with a Q(10) of approximately 3 both for fast or slow conducting fibres. Amplitude and energy of the motor responses also showed an inverse correlation with temperature, but were influenced by a more complex set of factors (neuromuscular synapse, muscle membrane) than the simple neural conduction. CONCLUSIONS: Besides providing new normative data upon conduction in the rat tail nerves at different temperatures, our results suggest that this method may represent an excellent tool to study models of peripheral-nerve conduction in vivo under various physiological and pathological conditions.

Measurement of skin temperature after infrared laser stimulation.

OBJECTIVES: Several types of lasers are available for eliciting laser evoked responses (LEPs). In order to understand advantages and drawbacks of each one, and to use it properly, it is important that the pattern of skin heating is known and duly considered. This study was aimed at assessing the skin temperature during and immediately after irradiation with pulses by Nd:YAP and CO(2) lasers. MATERIALS AND METHODS: The back of the non-dominant hand was irradiated in 8 subjects. Temperatures were measured by a fast analogical pyrometer (5 ms response time). Stimuli were tested on natural colour (white) and blackened skin. RESULTS: Nd:YAP pulses yielded temperatures that were correlated with pulse energy, but not with pulse duration; much higher temperatures were obtained irradiating blackened skin than white skin (ranges 100-194 degrees C vs 35-46 degrees C). Temperature decay was extremely slow in white skin, reaching its basal value in more than 30 s. CO(2) pulses delivered with power of 3W and 6W yielded temperatures of 69-87 degrees C on white skin, and 138-226 degrees C on blackened skin. Temperature decay was very fast (4-8 ms). CONCLUSIONS: Differences in peak temperatures and decay times between lasers and tested conditions depend on energy and volume of heated skin. The highest temperatures are reached with lesser degree of penetration, as in the case of CO(2) laser and blackened skin. Taking into account the temperature decay time of the skin, the minimum interstimulus interval to get reliable LEPs should be no less than 10 s for Nd:YAP and 100 ms for CO(2) laser. Another important practical consequence of the heating pattern is that the Nd:YAP pulses will activate warmth receptors more easily than CO(2).

Trigeminal sensory pathway function in patients with SUNCT.

OBJECTIVE: Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) is a rare primary headache whose origins are unclear. To seek information on its pathophysiology, we studied the trigeminal Abeta and Adelta pathways by recording trigeminal reflexes and laser evoked potentials (LEPs) in patients with SUNCT. METHODS: Trigeminal reflexes and LEPs were recorded in 11 consecutive patients. Ten patients had neuroimaging evidence documenting idiopathic SUNCT and one had a posterior fossa tumour that compressed the trigeminal nerve thus causing symptomatic SUNCT. RESULTS: Whereas the patients with idiopathic SUNCT had normal trigeminal reflex and LEP responses, the patient with symptomatic SUNCT had abnormal responses. CONCLUSIONS: Our neurophysiological findings show that idiopathic SUNCT spares the trigeminal sensory pathways whereas symptomatic SUNCT does not. SIGNIFICANCE: Neurophysiological testing can easily differentiate the idiopathic and symptomatic forms of SUNCT. It also suggests that the two forms are pathophysiologically distinct entities.

Adelta nociceptor response to laser stimuli: selective effect of stimulus duration on skin temperature, brain potentials and pain perception.

OBJECTIVE: To disclose a possible effect of duration of pulsed laser heat stimuli on Adelta nociceptor responses, skin temperature profiles, brain evoked potentials and pain perception. METHODS: We used a laser stimulator which works in the millisecond range and allows us to change the duration of the pulse while keeping the total energy of the stimulus constant. In 10 healthy volunteers, we measured the intensity of perceived pain with a 0-10 scale and the latency and amplitude of the early N1 and late N2 components of the scalp potentials evoked by laser pulses of equal energy and three different stimulus durations (2, 10, and 20 ms). Using a specifically developed pyrometer with a temporal resolution lower than 1 ms we also measured stimulus-induced changes of skin temperature. RESULTS: Stimulus duration significantly influenced temperature rise times, pain perception, and brain potentials. Shorter stimulus durations yielded steeper slopes in the skin temperature profiles and higher pain ratings, shortened the latency of the N1 and N2 components, and increased the amplitude of N1. CONCLUSIONS AND SIGNIFICANCE: The shorter stimulus duration shortens receptor activation times and yields a more synchronous afferent volley, thus providing a stronger spatial-temporal summation at central synapses that enhances intensity of first pain and brain potentials. This may prove useful in clinical applications.

[Prevalence of renal artery stenosis in patients undergoing cardiac catheterization: when should abdominal aortography be performed? Results in 467 patients]. / Prévalence des sténoses des artères rénales dépistées au cours de coronarographies diagnostiques: dans quels cas doit-on réaliser une aortographie abdominale? A propos de 467 patients.

PURPOSE: To define a subgroup of patients at increased risk of renal artery stenosis (RAS) in a population of patients undergoing cardiac catheterization. MATERIALS AND METHODS: A total of 467 patients (mean age of 64 Years +/-11) underwent cardiac catheterization and aortography Results were evaluated to detect correlations between the presence or absence of RAS and clinical and biological parameters. RESULTS: A total of 42 (9%) patients had a renal artery stenosis. Univariate analysis defined parameters correlated with the presence of RAS: systolic blood pressure (p=0.03), pulse pressure (p=0.005), age (p<0.0001), creatinine clearance (p<0.0001), 2-vessel (p=0.028) and 3-vessel (p=0.037) coronary artery diseases. Multivariate analysis showed that the presence of RAS correlated to creatinine clearance (p=0.02) and 2-vessel coronary artery disease. A creatinine clearance between 30 and 60 ml/min and multi-vessel coronary artery disease defined a subgroup at increased risk of RAS with sensitivity, specificity, positive and negative predictive values of: 47.6, 90.1, 32.3 and 94.6%. The prevalence of renal artery stenosis was 5.2% when both parameters were absent. CONCLUSION: Patients with mild renal insufficiency and multi-vessel coronary artery disease defined a subgroup of patients at increased risk of RAS (32.5%) that may benefit from abdominal aortography performed at the time of cardiac catheterization.

Excitability of the Adelta nociceptive pathways as assessed by the recovery cycle of laser evoked potentials in humans.

To investigate the excitability of Adelta nociceptive pathways and the nature of the vertex laser evoked potentials (LEPs), we studied the recovery cycle of the P2-LEP component and compared it with that of the P200 of the somatosensory evoked potential (SEP). Using two identical CO(2)-laser stimulators, we delivered paired stimuli to two adjacent skin spots on the hand at interstimulus intervals ranging from 250 ms to 2 s. The test P2-LEP was strongly inhibited at the 250-ms interstimulus interval ( P<0.01) and progressively recovered by the 2-s interval. The P200-SEP, after paired stimuli to the median nerve, showed a time course even slower than the P2-LEP ( P<0.01). Besides providing the LEP recovery curve in normal subjects, our findings indicate that the P2-LEP relays through a number of synapses similar to (or even lower than) that for the P200-SEP, thus lending further support to the view that the nociceptive P2-LEP is not an endogenous potential equivalent to the P300.

Prevalence of carotid stenosis in type 2 diabetic patients asymptomatic for cerebrovascular disease.

Stroke, with an incidence of 2.5 x 10(3) yr(-1) (95% CI, 2.3-2.8 x 10(3) yr(-1)), is the third most frequent cause of death and the first cause of disability in western society. Diabetes is an important risk factor for ischaemic stroke, second only to hypertension, whereas it does not seem to be associated with an increased risk of haemorrhagic stroke. The incidence of stroke in men and women between 45 and 74 yr has been found to be 2.5 and 3.5 times higher in diabetics than in non-diabetic subjects, with a relative risk higher in females than in males with diabetes and greater in both sexes in the 50-to-60-yr age group but decreased in subjects who were 70 and above. It is known that there is an association between ischaemic stroke and carotid stenosis. However, the prevalence of carotid stenosis in Type 2 diabetes mellitus (T2DM) patients has not been well investigated, mainly in the Italian diabetic population. Therefore, the aim of this study was to evaluate the prevalence of carotid artery stenosis in a population of T2DM patients asymptomatic for cerebrovascular disease selected from the files of the Diabetes Clinics, and from the computerised files of General Practitioners (GPs). Three hundred and sixty-five subjects were examined: 187 were non-diabetic (89 males, 98 females) and 178 were T2DM patients (82 males, 96 females). The mean age of all the subjects was 67 +/- 7.8 yr; 66 +/- 7.9 for the non-diabetic subjects and 67 +/- 7.5 yr in the diabetic subjects. In the echo-Doppler examination of the carotid, a degree of stenosis ranging 10-99% was recorded in 143/365 subjects (39.1%), 49/187 non-diabetics (26.2%) and 94/178 diabetics (52.8%). The differences were highly significant (p < 0.001). Severe stenosis was recorded in 17/143 subjects (12%); 12 of these were diabetic (70%) and 5 non-diabetic (30%). The diabetics were three times more likely to develop carotid stenosis than the non-diabetics with an odds ratio of 3.152, (95% CI, 2.032-4.889).

Unmyelinated trigeminal pathways as assessed by laser stimuli in humans.

Laser pulses excite superficial free nerve endings innervated by small-myelinated (Adelta) and unmyelinated (C) fibres. Whereas laser-evoked scalp potentials (LEPs) are now reliably used to assess function of the Adelta-fibre nociceptive pathways in patients with peripheral or central lesions, the selective activation of C-fibre receptors and recording of the related brain potentials remain difficult. To investigate trigeminal C-fibre function, we directed laser pulses to the facial skin and studied sensory perception and scalp evoked potentials related to Adelta- or C-fibre activation in healthy humans and patients--one having a bilateral facial palsy, two a trigeminal neuropathy, and two a Wallenberg syndrome. We also measured afferent conduction velocity and, with source analysis, studied the brain generators. Whereas laser pulses of low intensity and small irradiated area elicited pinprick sensations and standard Adelta-LEPs, laser pulses of very-low intensity and large irradiated area elicited warmth sensations and scalp potentials with a latency compatible with C-fibre conduction (negative wave 280 ms, positive wave 380 ms); the estimated conduction velocity was 1.2 m/s. The main waves of the scalp potentials originated from the anterior cingulate gyrus; they were preceded by activity in the opercular region and followed by activity in the insular region. The patient with bilateral facial palsy, who had absent trigeminal-facial reflexes, had normal Adelta- and C-related scalp potentials; the patients with trigeminal neuropathy, characterized by loss of myelinated and sparing of unmyelinated fibres, had absent Adelta- but normal C-related potentials; and the patients with Wallenberg syndrome had absent Adelta- and C-related potentials. We conclude that laser pulses with appropriate characteristics evoke brain potentials related to the selective activation of trigeminal nociceptive Adelta or thermal C fibres. The trigeminal territory yields rewarding LEP findings owing to the high density of thermal receptors and, because the short conduction distance, minimizes the problem of signal dispersion along slow-conducting unmyelinated afferents. The opercular-insular region and the cingulate gyrus are involved in the processing of C-fibre trigeminal inputs. The method we describe may prove useful in patients with lesions affecting the trigeminal thermal pain pathways.

Endothelin-1 plasma levels in cluster headache.

BACKGROUND AND OBJECTIVE: A role for endothelin-1, a potent vasoconstrictor peptide, in some cerebrovascular diseases has been proposed. To obtain preliminary data about peripheral concentrations of endothelin-1 in acute cluster headache, we measured the plasma endothelin-1 secretory pattern in 10 men with cluster during and independent of a headache attack. METHODS: We collected blood samples for plasma endothelin-1 determinations at 0, 15, 30, 45, 60, 90, and 120 minutes during a cluster attack and closely monitored blood pressures. We repeated the same sampling during an asymptomatic period. RESULTS: The mean values of plasma endothelin-1 (before a cluster headache, 3.3 +/- 0.3 pg/mL) significantly increased (F = 2.578, P < .05) during an attack, reaching their peak at 30 minutes (5.0 +/- 0.5 pg/mL, P < .05). We found no significant variations in mean arterial pressure. CONCLUSION: Endothelin-1 may play a role in the pathophysiology of cluster attacks. The increase in plasma observed during cluster attacks may be linked to alterations in systemic hemodynamics and vascular tone.

Drug-resistant cluster headache responding to gabapentin: a pilot study.

Prompted by the results of gabaergic drugs, such as valproate and topiramate, we performed this pilot study to assess the effect of gabapentin in cluster headache. Eight patients suffering from episodic cluster headache and four suffering from chronic cluster headache were studied. All of them had failed to respond to traditional prophylactic drugs. The design of the study was an open trial. The main parameter for effectiveness was the number of daily attacks. Gabapentin was given at the daily dosage of 900 mg. All patients were pain free after a maximum of 8 days after starting therapy, with a bout duration thus reduced to 16-40% of the average previous bouts (only applies to episodic cluster patients). We hypothesize that the gabaergic action of gabapentin, perhaps combined with other mechanisms, such as calcium channel blockade, may be responsible for its remarkable effects on cluster headache.

Head extensor reflex evoked by trigeminal stimulation in humans.

OBJECTIVE: Excitatory and inhibitory responses have been recognized in human cervical muscles following trigeminal stimulation. However, no evidence has so far been published of a crossed, short-latency, excitatory response resembling the early head extensor reflex seen in the cat. We seek its existence in humans. METHODS: The study was carried out in 14 voluntary healthy subjects. Percutaneous and surface electrical stimulation of the supraorbital and infraorbital nerves was performed with single, double and repetitive stimuli. Signals were recorded from the relaxed splenius and sternomastoid muscles bilaterally. RESULTS: Percutaneous stimulation of infraorbital nerve with single stimuli evoked an early response in the contralateral splenius muscle, with onset latency ranging from 11 to 14 ms (HR1). This response was greatly facilitated by double or repetitive stimuli. Single stimuli also gave rise to two larger responses in all 4 muscles in the latency ranges 50-70 ms (HR2) and 100-160 ms (HR3). Surface stimulation of one nerve alone could not elicit any early activity. Single surface stimuli delivered simultaneously to the supraorbital and infraorbital nerves evoked HR1 in only 5 subjects. CONCLUSIONS: We detected a crossed early reflex of the head extensor muscles to trigeminal stimuli. Its timing is similar to the 8-ms response seen in cats. The evidence provided suggests that the reflex is mediated by an oligosynaptic circuit and that it needs a strong spatial summation at central synapses.

Small-fiber dysfunction in trigeminal neuralgia: carbamazepine effect on laser-evoked potentials.

BACKGROUND: In patients with trigeminal neuralgia, results of clinical examination of sensory function are normal. Reflex and evoked potential studies have already provided information on large-afferent (non-nociceptive) function. Using laser-evoked potentials (LEP), the authors sought information on small-afferent (nociceptive) function. METHODS: The brain potentials evoked by CO(2)-laser pulses directed to the perioral and supraorbital regions were studied in 67 patients with idiopathic or symptomatic trigeminal neuralgia and 30 normal subjects. Of the 67 patients, 49 were receiving carbamazepine. RESULTS: All patients with symptomatic and 51% of those with idiopathic trigeminal neuralgia had frankly abnormal LEP on the painful side. The mean latency was significantly higher and mean amplitude lower on the painful than the nonpainful side. However, even on the nonpainful side, the mean latency was significantly longer than that of the age-matched controls. The nonpainful-side latency correlated significantly with the carbamazepine dose. CONCLUSIONS: LEP detect severe impairment of the nociceptive afferent system on the painful side of patients with idiopathic as well as symptomatic trigeminal neuralgia. A dysfunction of small-myelinated afferents may play an important role in the pathophysiology of neuralgic pain. Carbamazepine markedly dampens these brain potentials. The authors propose that this effect may result from inhibition of nociceptive transmission in the cingulate gyrus.

Low-dose gabapentin combined with either lamotrigine or carbamazepine can be useful therapies for trigeminal neuralgia in multiple sclerosis.

Paroxysmal symptoms occur frequently in multiple sclerosis (MS). Usually they are treated with carbamazepine (CBZ) and phenytoin, although these medications are often interrupted due to adverse effects. We report 11 MS patients with trigeminal neuralgia (TN): 6 intolerant to a therapeutic dosage of CBZ, showing serious adverse effects and subsequently treated with a combination of low-dose CBZ and gabapentin (GBP) (group 1); 5 treated with lamotrigine (LMT), showing adverse effects and subsequently treated with GBP (group 2). Subjective pain level and impairment in performing daily activities were rated utilizing a 3-point scale at time 0 and at optimal dosage time (T1). GBP was initiated at 300 mg daily and titrated, until pain control was achieved without new adverse effects, to a maximum dose of 1,200 mg daily. CBZ or LMT were reduced to a level which no longer produced adverse effects, although resulting in a lack of efficacy in relieving pain. Pain control was obtained in all patients but 1, with no side effects. The plasma level analysis, performed in 5 patients, resulted in normal values. The mean dosages at T1 were: group 1 CBZ 400 mg and GBP 850 mg daily; group 2 LMT 150 mg and GBP 780 mg daily. Combining drugs with complementary modes of action may provide a rational pharmacological approach to the management of TN in MS.

Cluster headache-like pain in multiple sclerosis.

We describe a case with simultaneous occurrence of cluster headache-like pain and multiple sclerosis. Both neuroimaging and neurophysiology (trigeminal evoked potentials) revealed a demyelination plaque in the pons, at the trigeminal root entry zone, on the side of pain. Although that type of lesion is usually associated with trigeminal neuralgia pain, we hypothesize that in this case it may be linked with the concomitant cluster headache, possibly by activation of trigemino-vascular mechanisms.