Didem Akcali

Does single cortical spreading depression elicit pain behaviour in freely moving rats

Introduction: Behavioural animal studies are critical, particularly to translate results to human beings. Cortical spreading depression (CSD) has been implicated in migraine pathogenesis. We aimed to investigate the effects of CSD on the behaviour of freely moving rats, since available CSD models do not include awake animals. Materials and methods: We developed a new model to induce single CSD by applying topical N-methyl-D-aspartate (NMDA) and employed a combination of an automated behavioural analysis system, video camera and ultrasonic vocalisation (USV) calls for the first time. Electrocorticograms were also studied during CSD in freely moving rats. Behaviour associated with cephalic pain was assessed in a group of rats that received sumatriptan. Cortical c-fos immunoreactivity was performed in order to confirm CSD. Results: NMDA induced single CSD in ipsilateral cortex, evoked freezing behaviour (P < 0.01) and increased the number of wet dog shakes (WDS; P < 0.01). Grooming, locomotion, eating, drinking, and circling were not significantly altered among groups. Ultrasonic vocalisations compatible with pain calls (22–27 kHz) were only detected in 3 out of 25 rats. Sumatriptan did not significantly reduce the freezing behaviour. CSD induced significant c-fos expression in ipsilateral cerebral cortex and amygdala (P < 0.01). Conclusions: CSD induces freezing behaviour by invoking anxiety/fear via amygdala activation in freely-moving rats. Single CSD is unlikely to lead to severe pain in freely-moving rats, though the development of mild or vague pain cannot be excluded. The relevance of rat behavioural responses triggered by CSD to migraine symptoms in humans needs further evaluation.

Aetiology of convulsions due to stellate ganglion block: a review and report of two cases

Stellate ganglion block is a selective sympathetic block that affects the ipsilateral head, neck, upper extremity and upper part of the thorax. Convulsions are a recognized complication of intra-arterial injection during stellate ganglion block. As central nervous system toxicity depends ultimately on the concentration of the local anaesthetics presented to the brain, the likely causative factors are discussed as well as the types of toxic symptoms and their onset times. The paper considers the aetiological factors of such convulsions resulting from stellate ganglion block in two patients.

Sex-Related Differences in Animal Models of Migraine Headache

(Headache 2011;51:891‐904)

The thalamic reticular nucleus is activated by cortical spreading depression in freely moving rats: prevention by acute valproate administration.

This study investigated the effect of repetitive cortical spreading depression (CSD) on behaviour and the anatomical and physiological patterns of cellular activation of cortical and subcortical areas in awake, moving rats. Rat behaviours in response to repetitive CSD events evoked by the application of KCl were quantified with electrophysiological recording. Immunohistochemistry was used to quantify anatomical regions of cellular activation. The effects of acute valproic acid administration on the behavioural parameters and cellular activation were evaluated. CSD significantly decreased locomotor activity and induced freezing in awake, moving rats, and stimulated c‐Fos expression in the cortex, trigeminal nucleus caudalis (TNC), and amygdala. CSD also resulted in a prominent increase in c‐Fos expression in the ipsilateral thalamic reticular nucleus (TRN) visual sector. Electrophysiological recordings revealed propagation of CSD into the TRN. Valproic acid pretreatment decreased the duration of CSD‐induced freezing episodes and reversed the CSD‐induced reduction in locomotor activity. Acute valproic acid administration also significantly blocked CSD‐induced c‐Fos expression in the TNC and TRN. These findings show that CSD events cause consistent behavioural responses and activate specific brain regions in awake, freely moving rats. Selective activation of TRN by CSD and the suppression of this activation by valproic acid suggest that this brain region may play an important role in migraine pathogenesis and may represent a novel target for migraine therapy.

Subclinical Dysfunction of Cochlea and Cochlear Efferents in Migraine: An Otoacoustic Emission Study

Otoacoustic emission (OAE) testing enables us to identify the cochlear component of a hearing disorder and to monitor objectively minute changes in cochlear status undetectable by other audiological methods. Contralateral sound-induced suppression is mediated by medial superior olivary complex efferents which induce hyperpolarization counteracting the amplifying effects of outer hair cell (OHC) activity. The aim of this study was to assess functions of cochlea and its efferents in migraine using OAE testing and contralateral suppression of transiently evoked OAEs (TEOAE). Fifty-three migraineurs (106 ears) and 41 healthy subjects (82 ears) were included and pure tone audiometry (PTA), speech discrimination scores (SDS), distortion product OAE (DPOAE), TEOAE and contralateral suppression of TEOAEs were tested. PTA and SDS of migraineurs and controls were not different (P > 0.05). DPOAEs were tested between 1 and 6 kHz and a significant difference was detected only at 5 kHz frequency, where DPOAE amplitudes in migraine with aura (MA) were lower than in controls (P < 0.03). The mean amplitudes of TEOAEs were statistically insignificant between controls and migraine groups. Contralateral sound stimulus induced significant decrease in amplitudes of TEOAE (P = 0.005) in controls. In patients with migraine without aura and MA, mean amplitudes of TEOAEs were not suppressed by contralateral sound stimulus (P > 0.05). As PTA, SDS and DPOAE tests demonstrate normal functioning of inner ear between 1 and 4 kHz, absence of suppression of the TEOAEs by contralateral sound stimulation indicates the presence of dysfunction either in the medial olivocochlear complex in the brainstem or at the synaptic transmission between olivocochlear efferents and OHCs in the cochlea. Disruption in the contralateral suppression may be one of the mechanisms predisposing to the phonophobia symptom associated with migraine headache.

Percutaneous pulsed radiofrequency reduces mechanical allodynia in a neuropathic pain model.

BACKGROUND: Neuropathic pain is a result of a primary lesion or dysfunction of the peripheral or central nervous system, and its treatment is challenging. Animal models have been helpful in understanding mechanisms of neuropathic pain and in developing new treatment strategies. In this study, we examined the effect of percutaneous pulsed radiofrequency (PRF), which is a minimally invasive pain treatment method, on mechanical allodynia in a neuropathic pain rat model. METHODS: Neuropathic pain was achieved in a peripheral nerve pain model by performing L5–6 spinal nerve ligation. On the 14th postoperative day, percutaneous PRF was applied to the plantar side of the left rear paw. Animals were evaluated for mechanical allodynia with both dynamic plantar aesthesiometer (DPA) (weight and paw withdrawal time) and von Frey filaments (VF) on the 14th postoperative day and 1, 3, 5, 7, 10, and 14 days after PRF treatment. Experiments were conducted in six groups: Sham-operated + placebo PRF 6 min, sham-operated + PRF 6 min, neuropathic (NP) + 2 min placebo PRF, NP + 2 min PRF, NP + 6 min placebo PRF, and NP + 6 min PRF. RESULTS: Allodynia developed in all animals in the NP groups compared to sham-operated animals (P = 0.0001). DPA and VF showed that PRF application for 2 min significantly improved allodynia on 1–14th post-PRF day, compared to placebo PRF (P = 0.0001). Although DPA (both weight and paw withdrawal time) did not show any therapeutic effect from 6 min PRF application on 1–14th post-PRF days (P = 1.00), VF demonstrated transient improvement for the first week, which disappeared on later evaluations of the 6 min PRF group. CONCLUSIONS: Percutaneous PRF is an effective treatment option in the NP pain model, and further studies are needed to clarify its underlying mechanisms of action.

Sex-related influences in migraine

Migraine is a common neurological disorder with significantly higher incidence and prevalence in women than men. The presentation of the disease in women is modulated by changes in sex hormones from adolescence to pregnancy and menopause. Yet, the effect of sex influences has often been neglected in both basic and clinical and in clinical management of the disease. In this review, evidence from epidemiological, clinical, animal, and neuroimaging studies on the significance of the sex‐related influences in migraine is presented, and the unmet needs in each area are discussed.

Anesthetic management of a child with Rubinstein-Taybi syndrome for cervical dermoid cyst excision

which are characteristics of this syndrome (Fig. 1). Thyroid ultrasonography showed a multilocular cystic 33 3 20mm mass anterior to the thyroid gland. There was no mass activity on thyroid scintigraphy. The total blood count and other laboratory test results were within normal ranges. No gastroesophageal reflux was observed on esophagogastrography. The right testis had not descended, and the left testis was retractile. The results of cranial computerized tomography and chromosomal analysis were normal. He had no cardiac defects. He was diagnosed as having the autosomal dominant mutagenic form of RTS. There was an uneventful history of operation and anesthesia for a midline neck mass diagnosed as a thyroglossal cyst that was performed at another center 1 year previously. On this occasion, the midline neck mass was above the previous one and was thought to be a recurrent thyroglossal cyst preoperatively. The patient’s height was 90cm (,3 percentile), and his weight was 14kg (3–10 percentiles). He fasted for 8h and was not premedicated before induction of anesthesia. His heart rate was 130 beats·min21 and his SpO2 was 99%. After preoxygenation, anesthesia was induced by 50% N2O/O2 mixture in sevoflurane via a face mask. After intravenous access had been obtained, 0.5mg kg21 of atracurium was injected, and endotracheal intubation was performed without difficulty with an uncuffed tube that had an internal diameter of 4.5mm. Anesthesia was maintained with 50% N2O/O2 mixture in sevoflurane. The neck mass was excised. At the end of anesthesia, spontaneous ventilation was promptly reestablished. After reversal of residual muscle paralysis with 0.5mg of neostigmine and 0.25mg of atropine, the endotracheal tube was removed. Rectal paracetamol was administered for postoperative pain. No significant problem was encountered during induction, maintenance, and extubation. The pathologic diagnosis of the mass was dermoid cyst.

Anatomy of Headache

Clinical human and experimental animal studies have facilitated our understanding of the essential structures in the initiation, transmission, modulation, and maintenance of headache. Pain-sensitive cranial structures, such as the dura mater encephali and large intracerebral blood vessels, and the cranial and cervical muscles and ligaments, which are innervated by primary afferent neurons originating from the trigeminal ganglia, take pivotal role in headache generation. Nociceptive impulses originated in the peripheral structures are then transmitted to central structures via second-order trigeminal neurons in the trigeminocervical complex in the brainstem. In addition to bottom organization of headache, top-down modulation of nociceptive stimuli from cranial structures through descending pathways is also discussed in this chapter.

Evaluation of pain and patient satisfaction by music therapy in patients with endoscopy/colonoscopy

BACKGROUND/AIMS Endoscopy and colonoscopy are frequently performed procedures to evaluate the gastrointestinal system. These procedures are sometimes disturbing and painful for the patient. In gastrointestinal suits, endoscopy and colonoscopy may be performed on awake or sedated patients. Music therapy is a common and non-pharmacological treatment for various medical conditions, pain, and anxiety. The aim of the present study was to add music therapy to sedation administered during endoscopy and colonoscopy. The effect of music treatment on drug consumption, anxiety, and pain was investigated. MATERIALS AND METHODS American Anesthesiologist Association I-III adult patients scheduled for endo/colonoscopy were randomized to music treatment and no music treatment groups. Patients with endoscopic ultrasound and endoscopic retrograde colangiopancreaticography were excluded from the study. Anxiety score and pain severity were evaluated before and after the procedure. Heart rate, mean arterial pressure, and oxygen saturation were recorded before, during, and after the procedure. Total drug consumption was recorded. Patient satisfaction and desire for the same protocol for recurrent procedures were investigated. RESULTS Music therapy added to deep sedation administered by anesthesiologists provided decreased anxiety score and propofol consumption. Patient satisfaction was increased, and patients reported a desire for the same protocol for recurrent procedures. CONCLUSION The present study may serve as the beginning of using music therapy for pain treatment in gastroenterology procedures in our hospital with/without sedation. Music and other non-pharmacological treatment methods must be remembered to increase patient comfort during enco/colonoscopies and other painful procedures.