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Biomedical subjects

Z Katsarava

Publications and source records attributed to Z Katsarava.

At least 19 recordsLinked to original sources

Incidence and predictors for chronicity of headache in patients with episodic migraine.

The authors followed 532 consecutive patients with episodic migraine (<15 days/month) for 1 year. Sixty-four patients (14%) developed chronic headache (>/=15 days/month). The odds ratios for developing CH were 20.1 (95% CI 5.7 to 71.5) comparing patients with a "critical" (10 to 14 days/month) vs "low" (0 to 4 days/month) and 6.2 (95% CI 1.7 to 26.6) in patients with an "intermediate" (6 to 9 days/month) vs "low" headache frequency and 19.4 (95% CI 8.7 to 43.2) comparing patients with and without medication overuse.

Adult↗

[Gordian knot: medication overuse headache].

Overuse of any kind of headache drugs may lead to the development of the medication overuse headache (MOH). Clinical features of MOH depend on the substance class that has been overused. Overuse of analgesics leads to a chronic tension-type like headache, the overuse of triptans to daily migraine-like headache or to the increase of migraine frequency. The delay between the drug overuse and onset of daily headache is shortest for triptans (1.7 years), longer for ergots (2.7 years) and longest for analgesics (4.8 years). Treatment includes withdrawal followed by structured acute therapy and initiation of specific prophylactic treatment for the underlying primary headache. The relapse rate after a successful withdrawal is about 30%. Predictors for relapse are tension-type headache and the overuse of analgesics in combination with codeine, caffeine or opioids.

Analgesics↗

The effect of multiple stimuli on the modulation of the 'nociceptive' blink reflex.

The 'nociceptive' blink reflex is a method of examining human trigeminal pain pathways. We explored temporal summation of this reflex by using a train of pulses, rather than a single pulse, and remote activation of diffuse noxious inhibitory control (DNIC), to improve reliability, flexibility and nociceptive specificity of this technique. The R2 component of the nociceptive blink reflex response (nR2) was assessed in 28 healthy volunteers using between 1 and 7 pulses per stimulus train (inter-pulse interval 5 ms). The effect of DNIC on single-, double-, and triple-pulse nR2 was investigated. Compared to single pulses, double and triple pulses increased the sensation of pain, reduced the tactile and pain thresholds, and facilitated the blink reflex responses (reduced onset latency, increased magnitude and persistence of nR2). The maximal reflex facilitation was achieved using a triple pulse. Higher pulse numbers had no additional facilitatory effect. Activation of the DNIC system using heterotopic pain suppressed the nR2 evoked by double and triple stimulation by 16 and 42%, respectively, but not the nR2 from a single pulse. Stimulation with double and triple pulses may be more suitable to study influences on nociceptive pathways than single pulses and may widen the methodological flexibility of the nociceptive blink reflex technique. This technique may be useful in studying the trigeminal nociceptive system with particular reference to primary headache disorders and their neuropharmacology.

Adult↗

[Recent new information on epidemiology of headache].

We reviewed the epidemiology of headache disorders for the most frequent primary headache-syndromes: migraine, tension-type headache and trigemino-autonomic headache syndromes. In the last years scientific data about headache disorders have increased. New studies investigated not only the prevalence of headaches, but also economic costs of this disorder. Epidemiologic headache research also investigates the quality of life.

Autonomic Nervous System Diseases↗

Differences of anti-nociceptive mechanisms of migraine drugs on the trigeminal pain processing during and outside acute migraine attacks.

The aim of this study was to investigate central anti-nociceptive mechanisms of i.v. acetylsalicylic acid (ASA) and oral zolmitriptan (ZOL) in migraine patients and healthy subjects using the 'nociceptive' blink reflex (nBR). Twenty-eight migraine patients received ASA (n = 14, 1000 mg i.v) or ZOL (n = 14, 5 mg p.o) during the acute migraine attack and interictally. Thirty healthy subjects received either ASA or ZOL vs. placebo using a double blind cross over design. nBR was recorded in all patients and subjects before, 60 and 90 min after treatment. ASA and ZOL did not inhibit nBR responses in healthy subjects. Both ASA and ZOL suppressed nBR responses (ASA by 68%, ZOL by 78%) only during the acute attack but not interictally. The data suggest, that the anti-nociceptive effects of migraine drugs on the trigeminal nociceptive processing are different during and outside an acute migraine attack.

Adult↗

Rates and predictors for relapse in medication overuse headache: a 1-year prospective study.

The authors prospectively studied 98 patients with medication overuse headache. The 1-year relapse rate was 38% but was lower for patients with migraine compared with tension-type headache (22% vs 73%, p < or = 0.002) and combination of migraine and tension-type headache (22% vs 77%, p < or = 0.0001). The rate was also lower for patients overusing triptans than ergots (19% vs 20%, NS) and analgesics (19% vs 58%, p < or = 0.001). The long-term success of withdrawal depends on the type of primary headache and the type of overused medication.

Adult↗

Abnormal habituation of 'nociceptive' blink reflex in migraine--evidence for increased excitability of trigeminal nociception.

We studied the habituation of the 'nociceptive' blink reflex (nBR) in 15 healthy subjects and 17 migraine patients interictally as well as during unilateral migraine headache within six hours of onset and after treatment. In healthy volunteers the mean regression coefficient (MRC) was - 3.9 following right sided and - 4.9 left sided stimulation. This equals an amplitude loss of 19.5% (5 x -3.9) and 24.5% (5 x -4.9), respectively, across five consecutive sweeps. An augmentation of nBR responses was found in migraine patients interictally: MRC = 3.3 following stimulation of the headache side (HA) and MRC = 4.0 of the non-headache side (non-HA). The differences were statistically significant (anova: d.f. = 1, F = 25.8, P < 0.001). During the migraine attack MRCs were negative both before (-5.0, HA and - 4.0, non-HA) and after treatment (-2.6, HA and - 1.9 non-HA) and significantly differed from those outside the migraine attack (anova: d.f. = 2, F = 12.4, P < 0.001). The demonstrated lack of habituation of the nBR responses indicates an abnormal trigeminal nociceptive processing in migraine patients outside the migraine attack.

Adult↗

Sensitization of trigeminal nociception specific for migraine but not pain of sinusitis.

Trigeminal pain processing was studied in 14 patients with unilateral migraine attacks and 14 age- and sex-matched patients with comparable unilateral headache from frontal sinusitis. Using a nociception-specific blink reflex method (nBR), a facilitation of nBR responses predominantly on the headache side was observed in migraine, but not in sinusitis. The facilitation of trigeminal nociception may be specific for migraine rather than a consequence of peripheral pain such as frontal sinusitis.

Acute Disease↗

Features of medication overuse headache following overuse of different acute headache drugs.

OBJECTIVE: To investigate pharmacologic features such as mean critical duration until onset of medication-overuse headache (MOH) (MCDO), mean critical monthly intake frequencies (MCMIF), and mean critical monthly dosages (MCMD) as well as specific clinical features of MOH after overuse of different acute headache drugs, with a focus on newly approved triptans. METHODS: In a prospective study 98 patients with MOH according to International Headache Society (IHS) criteria underwent standardized inpatient withdrawal from their medication. Patient diaries and structured interviews were used to calculate the MCDO, MCMIF, and MCMD for each substance group. RESULTS: The MCDO was shortest for triptans (1.7 years), longer for ergots (2.7 years), and longest for analgesics (4.8 years). The MCMIF was lowest for triptans (18 single doses per month), higher for ergots (37), and highest for analgesics (114). Although patients overusing ergots and analgesics typically had a daily tension-type headache, patients with triptan-induced MOH were more likely to describe a (daily) migraine-like headache or an increase in migraine frequency. CONCLUSION: Overuse of triptans leads to MOH faster and with lower dosages compared with ergots and analgesics. Clinical features of MOH depend on the type of overused headache medication. Pharmacologic and clinical characteristics of triptan-induced MOH call for the renewal of the current IHS classification.

Acute Disease↗

Acute migraine headache: possible sensitization of neurons in the spinal trigeminal nucleus?

OBJECTIVE: To investigate trigeminal sensory processing in patients with migraine using a novel "nociception-specific" blink reflex. METHODS: Seventeen patients with unilateral migraine headache were studied within 6 hours of onset. Blink reflexes were elicited with a standard stimulating electrode (standard blink reflex) and concentric stimulating electrode (nociception-specific blink reflex) during the acute migraine attack, after treatment with IV lysine acetylsalicylate (1,000 mg) or oral zolmitriptan (5 mg) and interictally. RESULTS: After standard stimulation, no differences were detected for the R1 and R2 onset latencies and areas under the curve (AUC) between the different time points and the headache and nonheadache side. Nociception-specific stimulation revealed a shortening of R2 onset latencies (44.3 +/- 5.4 ms for headache side vs 48.9 +/- 5.8 ms for nonheadache side) during the acute migraine attack compared with the headache-free interval (49.8 +/- 5.3 vs 49.8 +/- 4.5 ms). The AUC of the R2 increased on the headache side by 680% and on the nonheadache side by 230% compared with the headache-free interval. Drug treatment parallel to pain relief increased the onset latencies (zolmitriptan: 48.0 +/- 8.2 ms for headache side vs 52.3 +/- 7.6 ms for nonheadache side; lysine acetylsalicylate: 48.0 +/- 5.0 ms for headache side vs 51.2 +/- 5.6 ms for nonheadache side) and reduced the AUC of R2 (zolmitriptan by 45% and lysine acetylsalicylate by 48%). CONCLUSION: The data suggest temporary sensitization of central trigeminal neurons during acute migraine attacks.

Acute Disease↗

Optimized stimulation and recording parameters of human 'nociception specific' blink reflex recordings.

OBJECTIVE: Few non-invasive methods are available for studying trigeminal nociception in humans. The 'nociception specific' blink reflex (nBR) is elicited by a preferential stimulation of trigeminal nociceptive fibers and is highly sensitive to changes in trigeminal nociception. The aim of this study was to establish its optimal stimulation parameters. METHODS: The inter-individual variability of R2 responses (41 healthy subjects), symmetry of R2 responses after right vs. left sided stimulation (25 subjects), optimal stimulation parameters (3 groups, each 16 subjects) and re-test reliability over time (15 subjects) were studied. RESULTS: The nBR had a R2 response with a latency of 44.7+/-7.3ms, but no R1 response. The mean difference of R2 latencies (right vs. left sided stimulation) was 0.4+/-2.1(SD)ms, the mean ratio of the R2 response areas (RA) was 1.05+/-0.39 (SD). Thus, lateral differences of onset latencies greater than 4.6ms (0.4+4.2 (2SD)) or >1.83-fold (1.05+0.78 (2SD)) of RA can be assumed as outside of normal range. Long inter-block intervals of 7min minimized the cumulative habituation of R2 RAs to 23%, onset latencies remained constant. Re-test reliability over 4 weeks was high both for latencies (Crohnbach's alpha=0.85) and RAs (alpha=0.94). CONCLUSIONS: The nBR with the established stimulation parameters could be used for studying trigeminal nociception.

Adult↗

Clinical features of withdrawal headache following overuse of triptans and other headache drugs.

BACKGROUND: Complete withdrawal from headache medication is the treatment of choice for medication-overuse headache. Discontinuation of the overused headache medication, however, results in the development of withdrawal headache, often associated with nausea, vomiting, and sleep disturbances. METHOD: In a prospective study of 95 patients, the authors investigated the duration and severity of withdrawal headache after overuse of various headache drugs, including single and combination analgesics, ergots, and triptans. All patients underwent standard inpatient withdrawal therapy for 14 days. RESULTS: The duration of withdrawal headache was shorter in patients overusing triptans (4.1 days) than in patients overusing ergots (6.7 days) or analgesics (9.5 days; p < 0.002). The mean headache intensity on the first day of withdrawal did not differ between the groups (p = 0.821). By day 14, however, it was lower in patients overusing triptans (0.08) than in patients overusing ergots (0.4) or analgesics (0.9; p < 0.005). Rescue medication was requested less by patients undergoing triptan withdrawal (0.25 requests) than by patients undergoing ergot withdrawal (1.25) or analgesic withdrawal (1.85; p < 0.05). Similar to findings in the entire patient population, withdrawal headache was shorter and less severe in migraineurs overusing triptans than in those overusing ergots or analgesics. Because only patients with migraine, but no patient with tension-type headache, overused triptans, withdrawal headache was shorter in the group of patients with migraine alone (6.7 days versus 9.6 days for patients with tension-type headache and 8.5 days for patients with combination headache, p < 0.02). CONCLUSION: The duration and severity of withdrawal clearly depend on the type of overused headache drug only.

Adult↗

An in vivo rat model to study calcitonin gene related peptide release following activation of the trigeminal vascular system.

Calcitonin gene related peptide (CGRP) released from the C-fibers projecting from the trigeminal ganglion to the meninges has been suggested to play a crucial role in the pathophysiology of headache, particularly migraine. In humans it has been shown that CGRP is released during migraine-attacks, and this is attenuated by the administration of typical anti-migraine drugs such as dihydroergotamine or sumatriptan. We describe a new rat model which allows the study of CGRP release from the meninges into venous blood following activation of the trigeminal vascular system. The effects of classical and new anti-migraine drugs such as acetylsalicylic acid (ASA), sumatriptan and the new high efficacy 5-HT1B/1D agonist donitriptan (4-[4-[2-(2-aminoethyl)-1H-indol-5-yloxyl]acetyl]piperazinyl-1-yl]benzonitrile) were evaluated in comparison with the established model of neurogenic inflammation in the meninges. Sumatriptan and donitriptan inhibited CGRP release as well as neurogenic inflammation. ASA, however, attenuated neurogenic inflammation, but not CGRP release, confirming the concept of prejunctional inhibition of CGRP release by 5-HT1B/1D receptors. This new model allows the further study of prejunctional pharmacology and mechanisms of neuropeptide release in the trigeminal vascular system, which might be crucial for the further development of potent, more effective anti-migraine drugs.

Animals↗

Drug-induced headache: long-term follow-up of withdrawal therapy and persistence of drug misuse.

Patients suffering from migraine, tension-type headache (TTH), or combined headache (CH) are at risk of developing drug-induced headache (DIH) due to regular use of analgesics, ergot alkaloids, and triptans. The aim of our study was to determine (1) the clinical features of DIH, (2) the outcome of withdrawal therapy using high methodological standards, and (3) predictors which could explain the high relapse rate (more than 40%) after a previously successful withdrawal therapy. We retrospectively reviewed 103 patients with migraine or TTH who underwent withdrawal therapy between 1994 and 1998. The long-term follow-up (2-4 years after therapy) was conducted by phone and by specially trained psychologists using a structured interview which enclosed characteristics of headache and medication behavior as well as patients global assessment of success. Complete sets of data were available from 83 patients (38 migraine, 26 TTH, 19 CH). The most frequently abused drugs were caffeine-combined analgesics (24%), followed by caffeine-combined ergotamines (19%), pure ergot alkaloids (17%), and monoanalgesics (17%). 48.5% of the patients suffered an abuse relapse within 4 years and developed the complete features of DIH again. Analgesic and ergot alkaloid combinations with caffeine lead significantly more often to a relapse. A long-term successful therapy is connected with a significant reduction of the frequency of headache attacks. Under relapse conditions, the patients reached their former headache frequency level. The data show a higher relapse rate than previously assumed and that certain substance groups bear a higher relapse risk.

Adult↗

Medication overuse headache.

The frequent use (>15 times/month) of medication for the treatment of acute migraine attacks may cause medication overuse headache. This kind of headache can be caused by the intake of a combination of analgesics, opioids, ergot alkaloids and triptans. The delay between first intake and these attacks is shortest for triptans (1-2 years), longer for ergots (3-5 years) and longest for analgesics (5-10 years). Treatment includes drug withdrawal followed by structured acute therapy and initiation of migraine prophylactic treatment.

Analgesics↗

Medication overuse headache: a focus on analgesics, ergot alkaloids and triptans.

Medication overuse headache (MOH, formerly known as drug-induced headache) is a well known disorder following the frequent use of analgesics or any other antiheadache drug including serotonin 5-HT(1B/D) agonists (triptans). Recent studies suggest clinical features of MOH depend on the substance class that has been overused. The delay between the frequent intake of any antiheadache drug and daily headache is shortest for triptans (mean 1.7 years), longer for ergot alkaloids (mean 2.7 years) and longest for analgesics (mean 4.9 years). Treatment includes withdrawal followed by structured acute therapy and initiation of specific prophylactic treatment for the underlying primary headache. The relapse rate within 6 months after successful withdrawal is about 30% and increases steadily up to 50% after 5 years.

Anti-Inflammatory Agents, Non-Steroidal↗

A new method to increase nociception specificity of the human blink reflex.

OBJECTIVE: The medullary R2 response of the blink reflex can be elicited by innocuous and noxious stimuli. The purpose of this study was to elicit a nociception specific R2 response with a new surface electrode. METHODS: In 10 healthy subjects the blink reflex was elicited using a standard (10-15 mA) and a new concentric surface electrode type (0.6-1.6 mA) which produces a pin-prick-like pain. RESULTS: After topical local anaesthesia with lignocaine/prilocaine R1 was unchanged, R2 was attenuated by 12% after standard stimulation but was almost abolished (-91%) with the new electrode type. CONCLUSION: Stimulation with low stimulus intensities but electrode-dependent high current density allows preferential depolarization of superficial nociceptive A-delta fibres. This new method is less traumatic than others and is useful in the study of trigeminal nociception.

Adult↗