Quantitative assessment of nociceptive processes in conscious dogs by use of the nociceptive withdrawal reflex

OBJECTIVE: To investigate the feasibility of evoking the nociceptive withdrawal reflex (NWR) from fore and hind limbs in conscious dogs, score stimulus-associated behavioral responses, and assess the canine NWR response to suprathreshold stimulations. ANIMALS: 8 adult Beagles. PROCEDURE: Surface electromyograms evoked by transcutaneous electrical stimulation of ulnaris and digital plantar nerves were recorded from the deltoideus, cleidobrachialis, biceps femoris, and tibialis cranialis muscles. Train-of-five pulses (stimulus(train)) were used; reflex threshold (I(t train)) was determined, and recruitment curves were obtained at 1.2, 1.5, and 2 x I(t train). Additionally, a single pulse (stimulus(single)) was given at 1, 1.2, 1.5, 2, and 3 x I(t train). Latency and amplitude of NWRs were analyzed. Severity of behavioral reactions was subjectively scored. RESULTS: Fore- and hind limb I(t train) values (median; 25% to 75% interquartile range) were 2.5 mA (2.0 to 3.6 mA) and 2.1 mA (1.7 to 2.9 mA), respectively. At I(t train), NWR latencies in the deltoideus, cleidobrachialis, biceps femoris, and cranial tibialis muscles were not significantly different (19.6 milliseconds [17.1 to 20.5 milliseconds], 19.5 milliseconds [18.1 to 20.7 milliseconds], 20.5 milliseconds [14.7 to 26.4 milliseconds], and 24.4 milliseconds [17.1 to 40.5 milliseconds], respectively). Latencies obtained with stimulus(train) and stimulus(single) were similar. With increasing stimulation intensities, NWR amplitude increased and correlated positively with behavioral scores. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, the NWR can be evoked from limbs and correlates with behavioral reactions. Results suggest that NWR evaluation may enable quantification of nociceptive system excitability and efficacy of analgesics in individual dogs.

Sonographic visualization and ultrasound-guided block of the third occipital nerve: prospective for a new method to diagnose C2-C3 zygapophysial joint pain

BACKGROUND: Chronic neck pain after whiplash injury is caused by cervical zygapophysial joints in 50% of patients. Diagnostic blocks of nerves supplying the joints are performed using fluoroscopy. The authors' hypothesis was that the third occipital nerve can be visualized and blocked with use of an ultrasound-guided technique. METHODS: In 14 volunteers, the authors placed a needle ultrasound-guided to the third occipital nerve on both sides of the neck. They punctured caudal and perpendicular to the 14-MHz transducer. In 11 volunteers, 0.9 ml of either local anesthetic or normal saline was applied in a randomized, double-blind, crossover manner. Anesthesia was controlled in the corresponding skin area by pinprick and cold testing. The position of the needle was controlled by fluoroscopy. RESULTS: The third occipital nerve could be visualized in all subjects and showed a median diameter of 2.0 mm. Anesthesia was missing after local anesthetic in only one case. There was neither anesthesia nor hyposensitivity after any of the saline injections. The C2-C3 joint, in a transversal plane visualized as a convex density, was identified correctly by ultrasound in 27 of 28 cases, and 23 needles were placed correctly into the target zone. CONCLUSIONS: The third occipital nerve can be visualized and blocked with use of an ultrasound-guided technique. The needles were positioned accurately in 82% of cases as confirmed by fluoroscopy; the nerve was blocked in 90% of cases. Because ultrasound is the only available technique today to visualize this nerve, it seems to be a promising new method for block guidance instead of fluoroscopy.

Ultrasound-guided blocks of the ilioinguinal and iliohypogastric nerve: accuracy of a selective new technique confirmed by anatomical dissection

BACKGROUND: Ilioinguinal and iliohypogastric nerve blocks may be used in the diagnosis of chronic groin pain or for analgesia for hernia repair. This study describes a new ultrasound-guided approach to these nerves and determines its accuracy using anatomical dissection control. METHODS: After having tested the new method in a pilot cadaver, 10 additional embalmed cadavers were used to perform 37 ultrasound-guided blocks of the ilioinguinal and iliohypogastric nerve. After injection of 0.1 ml of dye the cadavers were dissected to evaluate needle position and colouring of the nerves. RESULTS: Thirty-three of the thirty-seven needle tips were located at the exact target point, in or directly at the ilioinguinal or iliohypogastric nerve. In all these cases the targeted nerve was coloured entirely. In two of the remaining four cases parts of the nerves were coloured. This corresponds to a simulated block success rate of 95%. In contrast to the standard 'blind' techniques of inguinal nerve blocks we visualized and targeted the nerves 5 cm cranial and posterior to the anterior superior iliac spine. The median diameters of the nerves measured by ultrasound were: ilioinguinal 3.0x1.6 mm, and iliohypogastric 2.9x1.6 mm. The median distance of the ilioinguinal nerve to the iliac bone was 6.0 mm and the distance between the two nerves was 10.4 mm. CONCLUSIONS: The anatomical dissections confirmed that our new ultrasound-guided approach to the ilioinguinal and iliohypogastric nerve is accurate. Ultrasound could become an attractive alternative to the 'blind' standard techniques of ilioinguinal and iliohypogastric nerve block in pain medicine and anaesthetic practice.

Spastin in the human and mouse central nervous system with special reference to its expression in the hippocampus of mouse pilocarpine model of status epilepticus and temporal lobe epilepsy

In the present in situ hybridization and immunocytochemical studies in the mouse central nervous system (CNS), a strong expression of spastin mRNA and protein was found in Purkinje cells and dentate nucleus in the cerebellum, in hippocampal principal cells and hilar neurons, in amygdala, substantia nigra, striatum, in the motor nuclei of the cranial nerves and in different layers of the cerebral cortex except piriform and entorhinal cortices where only neurons in layer II were strongly stained. Spastin protein and mRNA were weakly expressed in most of the thalamic nuclei. In selected human brain regions such as the cerebral cortex, cerebellum, hippocampus, amygdala, substania nigra and striatum, similar results were obtained. Electron microscopy showed spastin immunopositive staining in the cytoplasma, dendrites, axon terminals and nucleus. In the mouse pilocarpine model of status epilepticus and subsequent temporal lobe epilepsy, spastin expression disappeared in hilar neurons as early as at 2h during pilocarpine induced status epilepticus, and never recovered. At 7 days and 2 months after pilocarpine induced status epilepticus, spastin expression was down-regulated in granule cells in the dentate gyrus, but induced expression was found in reactive astrocytes. The demonstration of widespread distribution of spastin in functionally different brain regions in the present study may provide neuroanatomical basis to explain why different neurological, psychological disorders and cognitive impairment occur in patients with spastin mutation. Down-regulation or loss of spastin expression in hilar neurons may be related to their degeneration and may therefore initiate epileptogenetic events, leading to temporal lobe epilepsy.

Extended resection for thyroid disease has less operative morbidity than limited resection

BACKGROUND: Theodor Kocher, surgeon and Nobel laureate, has influenced thyroid surgery all over the world: his treatment for multinodular goiter-subtotal thyroidectomy-has been the "Gold Standard" for more than a century. However, based on a new understanding of molecular growth mechanisms in goitrogenesis, we set out to evaluate if a more extended resection yields better results. METHODS: Four thousand three hundred and ninety-four thyroid gland operations with 5,785 "nerves at risk" were prospectively analyzed between 1972 and 2002. From 1972 to 1990, the limited Kocher resections were performed, and from 1991 to 2002 a more radical resection involving at least a hemithyroidectomy was performed. RESULTS: The incidence of postoperative nerve palsy was 3.6%; in the first study period and 0.9%; in the second (P < 0.001, Fisher's exact). Postoperative hypoparathyroidism decreased from 3.2%; in the first period to 0.64%; in the second (P < 0.01). The rate of reoperation for recurrent disease was 11.1%; from 1972 to 1990 and 8.5%; from 1991 to 2002 (P < 0.01). CONCLUSIONS: Extended resection for multinodular goiter not only significantly reduced morbidity, but also decreased the incidence of operations for recurrent disease. Our findings in a large cohort corroborate the suggestions that Kocher's approach should be replaced by a more radical resection, which actually was his original intention more than 130 years ago.

Effects of butorphanol on the withdrawal reflex using threshold, suprathreshold and repeated subthreshold electrical stimuli in conscious horses

OBJECTIVE: To assess the effects of a single intravenous dose of butorphanol (0.1 mg kg(-1)) on the nociceptive withdrawal reflex (NWR) using threshold, suprathreshold and repeated subthreshold electrical stimuli in conscious horses. STUDY DESIGN: 'Unblinded', prospective experimental study. ANIMALS: Ten adult horses, five geldings and five mares, mean body mass 517 kg (range 487-569 kg). METHODS: The NWR was elicited using single transcutaneous electrical stimulation of the palmar digital nerve. Repeated stimulations were applied to evoke temporal summation. Surface electromyography was performed to record and quantify the responses of the common digital extensor muscle to stimulation and behavioural reactions were scored. Before butorphanol administration and at fixed time points up to 2 hours after injection, baseline threshold intensities for NWR and temporal summation were defined and single suprathreshold stimulations applied. Friedman repeated-measures analysis of variance on ranks and Wilcoxon signed-rank test were used with the Student-Newman-Keul's method applied post-hoc. The level of significance (alpha) was set at 0.05. RESULTS: Butorphanol did not modify either the thresholds for NWR and temporal summation or the reaction scores, but the difference between suprathreshold and threshold reflex amplitudes was reduced when single stimulation was applied. Upon repeated stimulation after butorphanol administration, a significant decrease in the relative amplitude was calculated for both the 30-80 and the 80-200 millisecond intervals after each stimulus, and for the whole post-stimulation interval in the right thoracic limb. In the left thoracic limb a decrease in the relative amplitude was found only in the 30-80 millisecond epoch. CONCLUSION: Butorphanol at 0.1 mg kg(-1) has no direct action on spinal Adelta nociceptive activity but may have some supraspinal effects that reduce the gain of the nociceptive system. CLINICAL RELEVANCE: Butorphanol has minimal effect on sharp immediate Adelta-mediated pain but may alter spinal processing and decrease the delayed sensations of pain.

Ultrasound-guided blocks for the treatment of chronic pain

Ultrasound (US) is an emerging imaging technique in interventional pain management. The main advantages are the identification of soft tissues, vessels, and nerves, without exposing patients and personnel to radiation, the possibility to perform continuous imaging, and the visualization of the fluid injected in a real-time fashion. Possible applications are nerve blocks of the cervical and lumbar zygapophysial joints, stellate ganglion block, intercostal nerve blocks, occipital nerve blocks, blocks of the inguinal nerves, peripheral nerve blocks of the extremities, blocks of painful stump neuromas, caudal epidural injections, and injections of tender points. US may also be used for destructive procedures, such as cryoanalgesia, radiofrequency lesions, or chemical neurolysis. The increasing published data available suggest that US has a potential usefulness in interventional pain management, but also limitations. There is still a need for clinical trials investigating efficacy and safety of US-guided pain procedures. Until these studies are made, fluoroscopy or computed tomography remain the gold standard for most interventional pain procedures.

Radiological anatomy of the obturator nerve and its articular branches: basis to develop a method of radiofrequency denervation for hip joint pain

OBJECTIVE: A previous study of radiofrequency neurotomy of the articular branches of the obturator nerve for hip joint pain produced modest results. Based on an anatomical and radiological study, we sought to define a potentially more effective radiofrequency method. DESIGN: Ten cadavers were studied, four of them bilaterally. The obturator nerve and its articular branches were marked by wires. Their radiological relationship to the bone structures on fluoroscopy was imaged and analyzed. A magnetic resonance imaging (MRI) study was undertaken on 20 patients to determine the structures that would be encountered by the radiofrequency electrode during different possible percutaneous approaches. RESULTS: The articular branches of the obturator nerve vary in location over a wide area. The previously described method of denervating the hip joint did not take this variation into account. Moreover, it approached the nerves perpendicularly. Because optimal coagulation requires electrodes to lie parallel to the nerves, a perpendicular approach probably produced only a minimal lesion. In addition, MRI demonstrated that a perpendicular approach is likely to puncture femoral vessels. Vessel puncture can be avoided if an oblique pass is used. Such an approach minimizes the angle between the target nerves and the electrode, and increases the likelihood of the nerve being captured by the lesion made. Multiple lesions need to be made in order to accommodate the variability in location of the articular nerves. CONCLUSIONS: The method that we described has the potential to produce complete and reliable nerve coagulation. Moreover, it minimizes the risk of penetrating the great vessels. The efficacy of this approach should be tested in clinical trials.

Sciatic nerve enlargement in the Klippel-Trenaunay-Weber syndrome

The case of a 35-year-old woman with Klippel-Trenaunay-Weber syndrome (KTWS) showing clinical symptoms of a peroneal nerve lesion is presented. An immense nerve enlargement along most of the sciatic, peroneal and tibial nerve was found to be due to a lipoma arising from the epi- and perineurium. Treatment consisted of extensive microsurgical neurolysis and excision of the tumor resulting in decompression of the affected nerves. Although rare, a perineural lipoma should be kept in mind in patients with KTWS showing neurological abnormalities.

Ultrasonography for depiction of brachial plexus injury

Recent development of ultrasonographic equipment has allowed improved spatial resolution for visualizing normal and pathologic conditions of peripheral nerves. Regarding the brachial plexus, only ultrasonographic studies that have described the normal appearance have been reported. To the best of our knowledge, no case report regarding the ultrasonographic description of a brachial plexus lesion has been published. We report the ultrasonographic findings of a brachial plexus injury after extirpation of a suspected enlarged supraclavicular lymph node.

Effects of Carnoy's solution on blood vessels of the axillary fossa of rats

Carnoy's solution is applied to reduce the recurrence of odontogenic keratocysts and unicystic ameloblastomas. The deleterious action of this fixative on nerves has been studied but no attention has been paid to its effects on nearby vessels. The aim of this study was to investigate the effects of Carnoy's solution on blood vessels. The rat axillary artery and vein were surgically exposed, soaked with Carnoy's solution and kept in place for 2, 5 or 10 min, depending on the treatment group. The 5-min group was followed for 1, 2 and 3 weeks postoperatively. The vessels in the 2-min and 5-min exposure groups showed histological changes to the vessels, represented by focal loss of the endothelium and hyalinization of the wall. These alterations increased in the 10-min group. The vessels in the 3-week observation period revealed signs of recovery. It is concluded that Carnoy's solution can damage blood vessels but the process is reversible for exposure times less than 5 min.

Ultrasound-guided needle positioning in sensory nerve conduction study of the sural nerve

OBJECTIVES: To evaluate the usefulness of ultrasound imaging to improve the positioning of the recording needle for nerve conduction studies (NCS) of the sural nerve. METHODS: Orthodromic NCS of the sural nerve was performed in 44 consecutive patients evaluated for polyneuropathy. Ultrasound-guided needle positioning (USNP) was compared to conventional "blind" needle positioning (BNP), electrically guided needle positioning (EGNP), and to recordings with surface electrodes (SFN). RESULTS: The mean distance between the needle tip and the nerve was 1.1 mm with USNP compared to 5.1 mm with BNP (p<0.0001). The mean amplitude of the sensory nerve action potential (SNAP) was 21 microV with USNP and 11 microV with BNP (p<0.0001). Compared to BNP, nerve-needle distances and SNAP amplitudes did not improve with EGNP. SNAP amplitudes recorded with SFN were significantly smaller than with BNP, EGNP and USNP. CONCLUSION: Ultrasound increases the precision of needle positioning markedly, compared to conventional methods. The amplitude of the recorded SNAP is usually clearly greater using USNP. In addition, USNP is faster, less painful and less dependent on the patient. SIGNIFICANCE: USNP is superior to BNP, EGNP, and SFN in accurate measurement of SNAP amplitude. It has a potential use in the routine near-nerve needle sensory NCS of pure sensory nerves.

Minimal local anesthetic volume for peripheral nerve block: a new ultrasound-guided, nerve dimension-based method

BACKGROUND AND OBJECTIVES: Nerve blocks using local anesthetics are widely used. High volumes are usually injected, which may predispose patients to associated adverse events. Introduction of ultrasound guidance facilitates the reduction of volume, but the minimal effective volume is unknown. In this study, we estimated the 50% effective dose (ED50) and 95% effective dose (ED95) volume of 1% mepivacaine relative to the cross-sectional area of the nerve for an adequate sensory block. METHODS: To reduce the number of healthy volunteers, we used a volume reduction protocol using the up-and-down procedure according to the Dixon average method. The ulnar nerve was scanned at the proximal forearm, and the cross-sectional area was measured by ultrasound. In the first volunteer, a volume of 0.4 mL/mm of nerve cross-sectional area was injected under ultrasound guidance in close proximity to and around the nerve using a multiple injection technique. The volume in the next volunteer was reduced by 0.04 mL/mm in case of complete blockade and augmented by the same amount in case of incomplete sensory blockade within 20 mins. After 3 up-and-down cycles, ED50 and ED95 were estimated. Volunteers and physicians performing the block were blinded to the volume used. RESULTS: A total 17 of volunteers were investigated. The ED50 volume was 0.08 mL/mm (SD, 0.01 mL/mm), and the ED95 volume was 0.11 mL/mm (SD, 0.03 mL/mm). The mean cross-sectional area of the nerves was 6.2 mm (1.0 mm). CONCLUSIONS: Based on the ultrasound measured cross-sectional area and using ultrasound guidance, a mean volume of 0.7 mL represents the ED95 dose of 1% mepivacaine to block the ulnar nerve at the proximal forearm.

High-resolution ultrasound confirms reduced synovial hyperplasia following rituximab treatment in rheumatoid arthritis

OBJECTIVE: To assess the response of RA patients to rituximab (RTX) treatment using a sensitive imaging technique for synovitis. METHODS: Twenty-three RA patients were treated with two 1000-mg infusions of the B-cell depleting antibody, RTX, in an observational protocol. Clinical response was assessed by the European League Against Rheumatism (EULAR) response criteria. High-resolution grey-scale and colour-coded power Doppler (PD) ultrasonography was performed at baseline and 6 months after RTX. The second to fifth MCP and PIP joints were bilaterally examined with joints in a neutral 0 position from a palmar view and scored from 0 to 3. RESULTS: Median disease activity score (DAS28) improved from 5.03 to 3.56 (P = 0.001), which corresponded to a EULAR moderate response in 11 of 23 patients and a EULAR good response in another 6 patients. Improved control of disease activity by RTX was also indicated by tapering of median daily corticosteroid doses from 10 to 5 mg, without flare ups. Mean grey-scale scores correlated with the swollen joint count at baseline (r = 0.484, P = 0.022) and month 6 (r = 0.519, P = 0.011). Mean grey-scale scores improved upon RTX from a 0.90 median (range 0.13-1.87) to 0.75 (range 0.19-1.50, P = 0.023). Frequency of PD positive joints was low (6.1%) at baseline and did not significantly change following RTX treatment. CONCLUSIONS: High-resolution grey-scale ultrasonography (US) examination confirmed reduced synovial hyperplasia, but the applied PD method displayed no significant changes. Therefore, only grey-scale US is recommended in follow-up examinations after RTX treatment.

Microvascular decompression for trigeminal neuralgia in the elderly: long-term treatment outcome and comparison with younger patients

OBJECTIVE: Multiple studies have proved that microvascular decompression (MVD) is the treatment of choice in cases of medically refractory trigeminal neuralgia (TN). In the elderly, however, the surgical risks related to MVD are assumed to be unacceptably high and various alternative therapies have been proposed. We evaluated the outcomes of MVD in patients aged older than 65 years of age and compared them with the outcomes in a matched group of younger patients. The focus was on procedure-related morbidity rate and long-term outcome. METHODS: This was a retrospective study of 112 patients with TN operated on consecutively over 22 years. The main outcome measures were immediate and long-term postoperative pain relief and neurological status, especially function of trigeminal, facial, and cochlear nerves, as well as surgical complications. A questionnaire was used to assess long-term outcome: pain relief, duration of a pain-free period, need for pain medications, time to recurrence, pain severity, and need for additional treatment. RESULTS: The mean age was 70.35 years. The second and third branches of the trigeminal nerve were most frequently affected (37.3%). The mean follow-up period was 90 months (range, 48-295 months). Seventy-five percent of the patients were completely pain free, 11% were never pain free, and 14% experienced recurrences. No statistically significant differences existed in the outcome between the younger and older patient groups. Postoperative morbidity included trigeminal hypesthesia in 6.25%, hypacusis in 5.4%, and complete hearing loss, vertigo, and partial facial nerve palsy in 0.89% each. Cerebrospinal fluid leak and meningitis occurred in 1 patient each. There were no mortalities in both groups. CONCLUSION: MVD for TN is a safe procedure even in the elderly. The risk of serious morbidity or mortality is similar to that in younger patients. Furthermore, no significant differences in short- and long-term outcome were found. Thus, MVD is the treatment of choice in patients with medically refractory TN, unless their general condition prohibits it.