Effect of prebiotic and probiotic supplementation on reduced pain in patients with fibromyalgia syndrome: a double-blind, placebo-controlled randomized clinical trial.

It has recently been observed that microorganisms in the gut can regulate brain processes through the gut microbiota-brain axis, affecting pain, depression, and sleep quality. Consequently, prebiotics and probiotics may potentially improve physical, psychological, and cognitive states in those with fibromyalgia syndrome (FMS) who have an altered microbiota balance. In a randomised, double-blind, placebo-controlled clinical trial to determine the effects of probiotic and prebiotic treatments on pain, sleep, quality of life, and psychological distress (depression and anxiety) in FMS, 53 female participants with FMS were randomised to receive either: 1) 4 × 1010 CFUs per day for the 18 patients in the probiotics group; 2) 10 g dose inulin per day for the 17 patients in the prebiotic group; or 3) a placebo for 8 weeks for the 18 patients in this group. The mean ages of the groups were similar and there was no significant difference between the groups. The impact of FMS on pain, sleep quality, quality of life, anxiety, and depressive symptoms were measured at baseline, 4 weeks, and 8 weeks post-intervention. Probiotic supplementation significantly decreased the Beck Depression Index (BDI), Beck Anxiety Index (BAI), and Pittsburgh Sleep Quality Index (PSQI) scores compared to baseline, while prebiotic supplementation only significantly decreased PSQI scores. Moreover, participants who received probiotic treatment presented a significantly reduced Visual Analogue Scale (VAS) score compared with those who received placebo treatment, after the interventions. Probiotic supplementation significantly improved sleep quality, depression, anxiety, and pain scores compared to those at baseline in FMS patients, while prebiotic supplementation significantly improved pain scores and sleep quality. The potential benefits of using probiotics for treatment management in FMS patients is supported by the results of the current study and might provide an important strategy to combat FMS-associated diseases.

The influence of stereotaxic lesions of claustrum on motor movements and behaviour in rats.

BACKGROUND: This study aimed to expand our existing information on changes in the regulation of motor movement and behaviour by investigating the effects of unilateral and bilateral lesions on the claustrum (CL). MATERIAL AND METHODS: 36 Wistar Albino adult male rats were randomly divided into six groups. An electrical lesion was created with a constant current source in the unilateral and bilateral anterior clastrum using a stereotaxic frame in rats. The lesioned groups and the control group underwent an automatic behaviour recording device such as mobilisation, freezing, eating, drinking behaviour, grooming, turning, etc. behaviour was recorded and analysed. Simultaneously, ultrasonic sounds in rats were examined with ultrasonic sound recording program. Anxiety was then reassessed with the elevated plus maze test. Data were compared with the control group. Rats were eventually sacrificed and the brain tissue was post-fixed. Histochemical examination was done and lesions' existence was confirmed. RESULTS: In this study, lesions of ventral of CL can cause increase in spontaneous behaviours such as freezing and rearing. And, it has been shown to cause a statistically significant change. In addition to the behavioural changes, right CL lesions have caused a significant increase in drinking behaviour associated with increased anxiety. All operated groups showed a significant decrease in clockwise and counterclockwise rotation movements. CONCLUSION: Experimental results show that CL lesions influence spontaneous behaviour which indicate the need for new studies to understand the role of CL in anxiety-depression.

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.

Visual and Postural Motion-Evoked Dizziness Symptoms Are Predominant in Vestibular Migraine Patients.

Background: Vestibular migraine (VM) is one of the most common underdiagnosed disorders. We aimed to study the clinical characteristics of VM patients who were referred to a neurology-headache unit by otolaryngology after exclusion of peripheral causes of vertigo. Methods: One hundred and one patients diagnosed with VM in the headache unit were included. Description of vestibular symptoms, demographic and clinical features, trigger factors, accompanying diseases, and response to vestibular-suppressant medications and prophylactic migraine treatment were evaluated. Results: Vestibular symptoms were triggered by daily head and body movements and mainly consisted of brief attacks lasting seconds (60.4% of patients) although the total duration of the vestibular episode lasted hours or days. Other aggravating factors were moving visual stimuli, passive motion, and visually busy environments. Visually induced vestibular symptoms were defined by 71.3% of the patients, and positional motion-induced vestibular symptoms were described by 82.2% of the patients. Vestibular symptoms were mainly defined as feeling the ground slipping from under their feet (40.6%), feeling like there is an earthquake or swaying (27.7%), sensation of rocking on a boat (26.7%), and sensation as if stepping on empty space (24.8%). The majority of the patients (83.2%) previously used vestibular-suppressant drugs, and these drugs were effective temporarily only in 12.9%. Conclusions: Chronic recurrent dizziness symptoms, rather than internal or external vertigo, are predominant in our VM patients. Recurrent brief dizziness attacks induced upon routine visual and/or postural motion, longstanding symptoms with limited response to vestibular suppressants, and precipitation by typical migraine triggers are suggestive of VM.

Epidural patch with autologous platelet rich plasma: a novel approach.

We aimed to perform an epidural patch using platelet rich plasma (PRP), which has the potential to regenerate and heal tissues via degranulation of platelets, in a 34-year-old parturient suffering from persistent post-dural puncture headache (PDPH) after failed epidural blood patch (EBP). After her admission to our unit, we reconfirmed the clinical and radiologic diagnosis of PDPH. Cranial MRI with contrast showed diffuse pachymeningeal thickening and contrast enhancement with enlarged pituitary consistent with intracranial hypotension. Clinical and radiological improvements were observed 1 week after the epidural patch using autologous PRP. Therefore, we recommend using autologous PRP for epidural patching in patients with incomplete recovery after standard EBP as a novel successful approach.

Nitroglycerin challenge induces lateralized headache in nasociliarynerve-ligated rats: implications for chronic migraine.

BACKGROUND/AIM: Chronic migraine is a common debilitating disease with limited treatment options. We aimed to develop a novel model for chronic migraine by ligating the nasociliary nerve (NCL) and administering nitroglycerin (NTG) to exacerbate acute headache attacks. MATERIALS AND METHODS: Exacerbation of the headache was induced by NTG (10 mg/kg, subcutaneously) administered to male Wistar rats (n = 36) 14 days following unilateral NCL. Cutaneous and cold allodynia was tested using Von Frey (VF) filaments and acetone, respectively. Elevated plus maze (EPM) results and c-fos immunoreactivity of TNC were investigated. RESULTS: NTG administration significantly decreased VF threshold values only in the nasociliary nerve (NCN) territory and the ipsilateral forepaw (P = 0.0001, P = 0.02). Cold allodynia developed in bilateral NCN territories (P = 0.013). The number/rate of entrance to open arms in the EPM was significantly decreased in NCN-ligated rats (P = 0.042, P = 0.035). Immunohistochemistry disclosed significantly increased c-fos-positive neurons in ipsilateral brainstem TNC compared to the contralateral side (brain stem LI ipsilateral 25.4 ± 4.7, contralateral 11.8 ± 1.9, P < 0.05) in chronic NCN-ligated rats exposed to acute NTG. CONCLUSION: The presented model provides a valid chronic migraine model relevant to humans, as NTG challenge in chronic NCL rats generated lateralized headache with cephalic and extracephalic allodynia, altered cold sensitivity, anxiety, and neuronal activation in the nociceptive laminae of brainstem trigeminal pain nuclei.

Metoclopramide inhibits trigeminovascular activation:evidence for effective acute attack treatment in migraine.

BACKGROUND/AIM: Metoclopramide is an effective and commonly used medication in acute migraine treatment but an experimental evidence base is lacking. We aimed to investigate the antimigraine effect of metoclopramide in a migraine model and whether the analgesic effect of metoclopramide was likely to be D2 receptor-mediated. MATERIALS AND METHODS: Cortical spreading depression (CSD) was used to model migraine in adult male Wistar rats. Five CSDs were induced by pinprick. Metoclopramide (two different doses), raclopride, or 0.9% saline were administered 30 min before CSD induction. Two hours after the experiments, brain tissues were examined for c-fos activation. RESULTS: In metoclopramide groups brain stem c-fos expression was significantly lower than in the CSD side of the saline group (P = 0.002). In the raclopride group, ipsilateral brain stem c-fos expression was also lower than in the saline group (P = 0.002). No difference in c-fos expression in the ipsilateral trigeminal nucleus caudalis between the raclopride and metoclopramide groups was observed (P > 0.05). CONCLUSION: Metoclopramide is shown to suppress trigeminovascular activation for the first time, providing an experimental basis for its role in migraine. The analgesic effect of metoclopramide is likely to be mediated by D2 receptors since raclopride, a selective D2 receptor antagonist, suppresses trigeminovascular activation similarly.

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. © 2016 Wiley Periodicals, Inc.

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.

Target-controlled infusion of remifentanil with propofol or desflurane under bispectral index guidance: quality of anesthesia and recovery profile.

BACKGROUND: Our objective was to examine the clinical properties of two anesthetic regimens, propofol target-controlled infusion (TCI), or desflurane using remifentanil TCI under bispectral index (BIS) guidance during ear, nose, and throat (ENT) procedures. METHODS: FORTY CONSENTING PATIENTS WHO SCHEDULED FOR ENT PROCEDURES WERE PROSPECTIVELY STUDIED AND WERE INCLUDED IN ONE OF THE TWO GROUPS: TCI group or desflurane (DES) group. General anesthesia was induced with 3 ng mL(-1) and 4 µg mL(-1) effect site concentrations (Ce) of remifentanil and propofol, respectively, with TCI system. After intubation, while propofol infusion was continued in the TCI group, it was ceased in the DES group and desflurane with an initial delivered fraction of 6% was administered. The Ce of propofol infusion and inspired fraction of desflurane was adjusted in order to keep BIS as 50 ± 10. RESULTS: General mean values of mean arterial pressure (MAP) and heart rate (HR) for the TCI group was significantly higher than DES group (89.3 mmHg and 72.4 bpm vs. 77.1 mmHg and 69.5 bpm). Early emergence from anesthesia did not significantly differ between the groups. The rate of patients' Aldrete score (ARS) to reach 10 was found to be 100% at the 15(th) min in both groups. CONCLUSIONS: Bispectral index guided combinations of remifentanil TCI either with propofol TCI or desflurane anesthetic regimens are both suitable for patients undergoing ENT surgery. The lower blood pressure in the remifentanil TCI with desflurane anesthetic regimens may be a significant advantage.

Sex-related differences in animal models of migraine headache.

Trigeminal nerve-mediated pain disorders such as migraine, temporomandibular joint disorder, and classical trigeminal neuralgia are more prevalent in women than in men. Female laboratory animals also show greater responses to various nociceptive stimuli than male animals. However, current knowledge of migraine pathogenesis is based primarily on experimental studies conducted in male animals and lack of migraine research with female animals limits clinical relevance. Migraine is triggered by any alteration in the intrinsic or extrinsic milieu and women at reproductive age are continuously prone to waxing and waning effects of female sex hormones. The experimental approach to this problem is complex because the rodent estrous cycle differs from the human cycle, and because exogenous hormone replacement in ovariectomized females has its limitations. The existence of multiple estrogen receptors in the trigeminal system also presents a challenge. Estrogens do not seem to directly affect calcitonin gene-related peptide or 5-HT(1D) receptors in the trigeminal system. Nonetheless, 2 estrogen receptors activate MAPK/ERK signaling pathway that mediates nociceptive processing in trigeminal nucleus caudalis. In addition, estrogen enhances susceptibility to cortical spreading depression, the neurobiological event underlying migraine aura, which may be independent of the estrous cycle. Further studies in female animals are required to clarify mechanisms underlying sex differences with respect to fluctuating sex hormones, cortical spreading depression, and excitability of the trigeminovascular system.

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.

[Burnout in healthcare workers in the Anesthesiology and Algology Departments in the Middle Anatolian region of Turkey]. / Iç Anadolu Bölgesinde anesteziyoloji ve algoloji çalisanlarinda tükenmislik durumu.

OBJECTIVES: Anesthesiology and Algology healthcare workers work under difficult conditions a majority of the time, and their physical and mental status must be determined in order to improve working conditions. In this study, the main goal was to evaluate the burnout level of Anesthesiology and Algology healthcare workers in the Middle Anatolian region of Turkey. METHODS: A questionnaire was sent to Anesthesiology and Algology healthcare workers of hospitals with an Algology clinic in the Middle Anatolian region and were returned by e-mail in March and April 2008. In the questionnaire, descriptive features and the Turkish validated Maslach burnout inventory (MBI) were evaluated. The MBI has 3 aspects: emotional exhaustion (EE), depersonalization (D) and personal accomplishment (PA). All questionnaires were evaluated by SPSS 11.5 program. RESULTS: 113 people were enrolled, of whom 18.8% (21) were specialist doctors and 41.1% (46) were residents. Among the doctors, the mean daily and weekly working periods were 10.3+/-2.3 and 61.3+/-19 hours, respectively. The period spent by doctors in Algology was 100% in 9.6%, 75% in 9.7% and 25% in 61.5%. Working conditions were evaluated, and 20.9% of healthcare workers were unsatisfied with the physical conditions, 19.3% with the working period and 52.5% with wages. MBIs in doctors were calculated as EE 14.7+/-5, D 5.7+/-3.5, and PA 21.6+/-4.2. CONCLUSION: This study revealed similar high burnout scores among healthcare workers, which reflect a serious burnout in the Anesthesiology and Algology group in Turkey. Burnout may be affected by dissatisfaction with working conditions. Improvement in physical conditions and reorganization to achieve psychological support might be helpful towards improving the health of healthcare workers.

[Reflex sympathetic dystrophy secondary to piriformis syndrome: a case report]. / Piriformis sendromuna ikincil gelisen refleks sempatik distrofi: Olgu sunumu.

Piriformis syndrome is a rare cause of hip and foot pain which may be due to sciatic nerve irritation because of anatomic abnormalities of sciatic nerve and piriformis muscle or herniated disc, facet syndrome, trochanteric bursit, sacroiliac joint dysfunction, endometriosis and other conditions where sciatic nerve is irritated. There has been no reflex sympathetic dystrophy (RSD) case presented due to piriformis syndrome before. A sixty-two-year-old female patient had right foot and hip pain (VNS: 8), redness and swelling in the foot since 15 days. Her history revealed long walks and travelling 3 weeks ago and sitting on the foot for a long time for a couple of days. Physical examination revealed painful hip movement, positive straight leg rise. Erythema and hyperalgesia was present in dorsum of the right foot. Right foot dorsiflexion was weak and hyperesthesia was found in right L4-5 dermatome. Medical treatment and ultrasound treatment to piriformis muscle was not effective. The patient was injected 40 mg triamcinolon and local anesthetic in right piriformis muscle under floroscopy by diagnosis of piriformis syndrome, neuropathic pain and RSD. Pain and hyperalgesia resolved and motor weakness was better. During follow-up right foot redness resolved and pain decreased (VNS: 1). In this case report, there was vascular, muscle and skeletal signs supporting RSD, which shows us the therapoetic effect of diagnostic piriformis injection. The patient history, physical examination and diagnostic tests were evaluated by a multidisciplinary team which contributed to the treatment.

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.

Do we need bispectral index monitoring during total intravenous anesthesia for lumbar discectomies?

The aim of this study was to investigate the effect of bispectral index (BIS) monitoring on hemodynamic parameters, drug consumption and awareness during total intravenous anesthesia (TIVA) with remifentanil and propofol in lumbar discectomies. After institutional ethical committee approval, ASAI-II 56 patients were divided as control and BIS groups. Anesthesia was induced by bolus remifentanil 1 mug/kg in both groups; propofol 2 mg/kg in was used in the control group while propofol was titrated to BIS 45- 65 values in the BIS group. Anesthesia was maintained by remifentanil and propofol infusions. Drug consumption, time to extubation and awareness were recorded. Demographic parameters were similar between the groups. Consumption of propofol was lower, and time to extubation was shorter in the BIS group; there was no difference between awareness among groups. BIS monitoring was helpful for propofol titration and decreased propofol consumption, but not enough to prevent reaction to noxious stimuli. Standard anesthesia titration considering hemodynamic parameters was enough for most ASA I-II patients for lumbar discectomies. BIS might be more helpful for patients who cannot show hemodynamic responses to noxious stimuli. More studies are needed to investigate the correlation between positioning and awareness using BIS monitoring.