Official reprint from UpToDate www.uptodate.com 2014 UpToDateAuthors Ivan Garza, MD Todd J Schwedt, MD, MSCI Section Editor Jerry W Swanson, MD Deputy Editor John F Dashe, MD, PhD Medication overuse headache: Etiology, clinical features, and diagnosisAll topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Oct 2014. | This topic last updated: Apr 28, 2014. INTRODUCTION Chronic daily headache is a descriptive term that encompasses several different specific headache diagnoses. Chronic daily headache types of long duration (ie, four hours or more) include chronic migraine, chronic tension-type headache, hemicrania continua, and new daily persistent headache. Medication overuse headache, a secondary headache disorder, frequently complicates management of multiple primary headache disorders. (See "Overview of chronic daily headache".)This topic will review the etiology, clinical features, and diagnosis of medication overuse headache (MOH). The treatment and prognosis of MOH is discussed separately. (See "Medication overuse headache: Treatment and prognosis".)BACKGROUND Medication overuse headache (MOH) is the term applied to headache occurring on 15 or more days per month developing as a consequence of regular overuse of acute or symptomatic headache medication for more than 3 months. It usually, but not invariably, resolves after the overuse is stopped [1]. MOH has also been termed analgesic rebound headache, drug-induced headache, and medication-misuse headache.Although not a primary type of chronic daily headache, MOH deserves proper coverage since it frequently coexists with primary chronic daily headache. In some cases, MOH may be associated with the development or maintenance of a chronic daily headache syndrome [2].PATHOPHYSIOLOGY Available evidence suggests all drugs used for the acute symptomatic treatment of headache can cause MOH in primary headache disorders [3,4]. The precise mechanisms that lead to MOH are still uncertain. However, multiple factors seem to play a role, including genetic predisposition, central sensitization, and biobehavioral factors.Genetic predisposition Various studies and clinical observations suggest that MOH is restricted to individuals who already have other headache disorders [3]. Furthermore, MOH does not develop de novo in individuals with no previous headache history [5].In a study of 103 patients using daily analgesics for arthritic pain but not for headache, only 8 patients (8 percent) had chronic daily headache, each of whom reported a previous history of episodic migraine [6]. This study supports the hypothesis that patients with previous episodic headaches may be susceptible to developing MOH and that analgesics may merely be a cofactor to the development of chronic daily headache in a genetically vulnerable individual.Patients with migraine and tension-type headache seem to have the highest potential for MOH [7]. However, MOH has also been described in cluster headache [8] and in hemicrania continua [9].Central sensitization Investigations demonstrating facilitation of trigeminal pain processing in patients with chronic headache have suggested that central sensitization, the same process that occurs in migraine, can lead to MOH [4,7,10]. Daily exposure to some triptans can downregulate Page 1of 9 Medication overuse headache: Etiology, clinical features, and diagnosis25/11/2014 http://www.uptodate.com/contents/medication-overuse-headache-etiolo...serotonin receptor subtypes 5-HT 1B and 5-HT 1D, and influence serotonin synthesis in the rat central nervous system [3,11].In humans, chronic exposure to triptans and other analgesics could lead to downregulation of serotonin receptors and changes in central inhibitory pathways that translate to an impairment of antinociceptive activity and a permanent feeling of head pain [3]. In support of this argument, neurophysiologic studies have shown facilitation of trigeminal and somatic nociceptive systems in MOH primarily mediated at a supraspinal level [12]. Another study in rats found that sustained or repeated triptan treatment induced pro-nociceptive neural adaptations and enhanced responses to nitric oxide, a known trigger of migraine headache in humans [13]. In addition, a report that measured glucose metabolism in migraineurs with MOH using 18-F-fluorodeoxyglucose positron emission tomography (FDG-PET) demonstrated reversible metabolic change in pain processing structures and persistent orbitofrontal hypofunction [14].Exposure to opiates also causes changes in the nervous system. Peripherally, the chronic administration of morphine results in increased expression of calcitonin gene-related peptide in primary afferent neurons [15]. Centrally, prolonged exposure to this opiate leads to increased descending facilitation from the rostral ventromedial medulla and increased excitatory neurotransmission at the level of the dorsal horn [15]. The combination of these may result in MOH [15].Biobehavioral factors It has been proposed that MOH is a biobehavioral disorder [16]. Some patients may have addictive disease, characterized by compulsive drug seeking and drug taking behavior despite negative consequences, as the basis of MOH. Other patients may use opiates or other drugs with sedative/anxiolytic effects to treat both pain and a coexistent anxiety disorder [16].Behaviors that may be particularly important in prompting and sustaining the overuse of medication include fear of headache, anticipatory anxiety, obsessional drug-taking behavior, and psychologic drug dependence [16]. In a prospective population-based longitudinal study of 32,067 adults from Norway, subjects using analgesics daily or weekly at baseline had a significantly increased risk of chronic pain 11 years later compared with those who never used analgesics [17]. Subjects with chronic migraine had the highest risk (relative risk 13.3, 95% CI 9.3-19.1).Further evidence that MOH is part of the spectrum of addictive disorders comes from the following observations:EPIDEMIOLOGY The prevalence of MOH in the general population is approximately 1 to 2 percent in most studies, and is higher in women than in men [4,10,20,21].Among patients who are seen at specialized headache centers, the prevalence of MOH is much higher, ranging from 4 to 80 percent [3,24,25].In a case-control study, patients with MOH derived from migraine (n = 41) had a significantly greater risk of substance-related disorders than those with episodic migraine (n = 41) (odds ratio 7.6, 95% CI 2.2-26) [18].In a prospective study of 1861 patients with chronic daily headache, 895 met criteria for probable MOH [19]. Substance dependence was significantly more frequent in patients with MOH than those without MOH (68 versus 20 percent).In a population-based study of over 49,000 subjects from Norway, the prevalence of chronic headache with analgesic overuse lasting three months or longer was 0.9 percent overall [22]. For women and men, the prevalence was 1.2 and 0.6 percent, respectively.In two smaller population studies from Spain, the prevalence of medication overuse headache was approximately 1.5 percent [20,23], with a female to male ratio of 17:1 [23].Page 2of 9 Medication overuse headache: Etiology, clinical features, and diagnosis25/11/2014 http://www.uptodate.com/contents/medication-overuse-headache-etiolo...Migraine is the most common primary headache disorder associated with MOH. In a meta-analysis of 29 studies that included a total of 2612 patients with chronic MOH, the underlying primary headache type was migraine, tension-type, or mixed/other in 65, 27, and 8 percent respectively [26].In addition to medication overuse, anxiety and depression may be risk factors for the evolution of migraine into MOH [18]. (See 'Biobehavioral factors' above.)A low socioeconomic status may be another risk factor for the development of MOH in migraineurs [27].Causal medications All acute symptomatic medications used to treat headaches have the potential for causing MOH [3]. However, the degree of risk differs depending upon the specific medication or class of medications. Based upon the literature and clinical experience, the risk appears to be highest with opioids, butalbital-containing combination analgesics, and aspirin/acetaminophen/caffeine combinations [10,28]. The risk for MOH with triptans is considered intermediate by some experts but high by others. The risk is lowest with nonsteroidal antiinflammatory drugs (NSAIDS).The evidence supporting these risks is illustrated by the following reports:The frequency of use for drugs implicated in MOH varies from country to country and is influenced by multiple factors [3], including the introduction of new acute headache medications over time. Butalbital is commonly overused in the United States, while simple analgesics and caffeine-containing drugs are most commonly associated with MOH in other parts of the world (eg, Spain and Brazil) [20,32]. Until A longitudinal population-based study that included 8219 subjects with episodic migraine (from a population sample of 120,000) showed that any use of barbiturates or opiates is associated with an increased risk of transformation from episodic to chronic migraine [29].A 2008 review of clinic-based and population studies found that, for opiates, the increased risk was more pronounced in men, and the critical dose of exposure was approximately eight days a month [29,30]. For barbiturates, the critical dose of exposure was approximately five days a month and the effect appeared greater in women. Triptans and NSAIDs induced migraine transformation only in those with a migraine frequency of 10 to 14 days per month.In a 2004 report from a tertiary headache center in New York of 169 patients who were followed in the last five years of the study (ie, the triptan era), the drugs most often associated with MOH included the following [2]:Butalbital containing combination products, 48 percent Acetaminophen, 46 percent Opioids, 33 percent Aspirin 32 percent Triptans, 18 percent Ergotamine tartrate, 12 percent NSAIDS other than ASA, 10 percent In a 2002 prospective German study of 98 patients with MOH, including 70 patients with migraine as the underlying primary headache type, overuse of triptans led to MOH sooner than overuse of ergots or analgesics, and did so at a lower frequency of use [31]. The mean interval until onset of MOH was shortest for triptans (1.7 years), longer for ergots (2.7 years), and longest for analgesics (codeine, barbiturates, caffeine combinations) (4.8 years) [31]. Similarly, the mean critical monthly intake frequency for MOH was lowest for triptans (18 single doses per month), higher for ergots (37 single doses per month), and highest for analgesics (114 single doses per month). However, the study was not designed to stratify risk among different substances.Page 3of 9 Medication overuse headache: Etiology, clinical features, and diagnosis25/11/2014 http://www.uptodate.com/contents/medication-overuse-headache-etiolo...the mid 1990s, combination analgesics with codeine or caffeine, or ergots combined with caffeine were the most frequently overused drugs associated with MOH in many European countries [24].With the introduction of triptans, the pattern of MOH may be changing. In a review of patients seen at a single headache center in the US from 1990 to 2005, MOH secondary to ergotamine decreased while MOH secondary to triptans increased [33].It is often difficult to identify a single causal substance for MOH, since many patients are overusing more than one drug [2,3]. In the Brazilian study of 133 patients with transformed migraine and symptomatic medication overuse, the frequencies of patients overusing one, two, or three medication categories were 55, 41, and 4 percent, respectively [32].CLINICAL FEATURES The development of MOH is typically preceded by an episodic headache disorder, typically migraine or tension-type headache, that has been treated with frequent and excessive amounts of acute symptomatic medications [10]. In clinical practice, MOH often manifests as a headache that is present or develops upon awakening [10]. Acute symptomatic treatment only provides transient relief, which leads to more acute symptomatic medication use.The severity, location, and type of head pain with MOH can vary significantly among different individuals, but headache commonly occurs daily or nearly daily [10]. Nausea, asthenia, difficulty concentrating, memory problems, and irritability can accompany MOH [10].To some extent, the clinical features of MOH may depend upon the type of headache medication that is overused [31]. In a prospective study of 98 patients with MOH, which included a majority of patients (71 percent) having migraine as the underlying type of headache, patients overusing ergots and analgesics (codeine, barbiturates, caffeine combinations) typically had a daily tension-type headache, while those with triptan-induced MOH were more likely to describe a daily migraine-like headache or an increase in migraine frequency [31].DIAGNOSIS The diagnosis of MOH is based upon clinical impression. The course of the headache disorder and the history of drug intake and intake frequency are the only available methods of diagnosis. A history of analgesic use averaging more than two to three days per week in association with chronic daily headache supports the diagnosis of MOH. The diagnosis is made when there is a pattern of frequent headaches that fulfill diagnostic criteria for MOH listed below. (See 'Diagnostic criteria' below.)Other disorders causing secondary headache must be excluded. (See 'Differential diagnosis' below.)In practice, some patients may be reluctant to fully disclose their drug history, particularly with regard to the frequency and amount consumed. In addition, it is not uncommon for patients to report prescription medications but not over-the-counter analgesics. In order to improve the accuracy of the drug history, it may be helpful to explain the concept of MOH to the patient, including the critical importance of medication use to development, diagnosis, and treatment of the disorder [3].Diagnostic criteria The diagnostic criteria for MOH (table 1) from the International Classification of Headache Disorders, 3rd edition (ICHD-3) are as follows [1]:Headache occurring on 15 or more days per month in a patient with a pre-existing headache disorder Regular overuse for more than three months of one or more drugs that can be taken for acute and/or symptomatic treatment of headache:Regular intake, for 10 days per month for >3 months, of ergotamines, triptans, opioids, or combination analgesics, or any combination of ergotamines, triptans, simple analgesics, nonsteroidal antiinflammatory drugs (NSAID) and/or opioids without overuse of any single drug or drug class alone or when the pattern of overuse cannot be reliably establishedPage 4of 9 Medication overuse headache: Etiology, clinical features, and diagnosis25/11/2014 http://www.uptodate.com/contents/medication-overuse-headache-etiolo...Patients who meet criteria for both medication overuse headache and chronic migraine are given both diagnoses [1]. (See "Chronic migraine", section on 'Diagnosis'.)Differential diagnosis Any form of chronic daily headache, whether primary or secondary, needs to be considered in the differential diagnosis of MOH. Primary headache subtypes of chronic daily headache include chronic migraine, chronic tension-type headache, hemicrania continua, and new daily persistent headache. (See "Chronic migraine" and "Tension-type headache in adults: Pathophysiology, clinical features, and diagnosis" and "Hemicrania continua" and "New daily persistent headache".)Other primary headache disorders, however, can also present as a chronic daily headache. The list includes cluster headache, SUNCT, hypnic headache, nummular headache, and chronic paroxysmal hemicrania. (See "Cluster headache: Epidemiology, clinical features, and diagnosis" and "Short-lasting unilateral neuralgiform headache attacks: Clinical features and diagnosis" and "Hypnic headache" and "Nummular headache" and "Paroxysmal hemicrania: Clinical features and diagnosis".)Appropriate diagnostic testing should be undertaken if clinical evaluation indicates the possibility of a serious medical or neurologic condition. (See "Evaluation of headache in adults" and "Evaluation of the adult with headache in the emergency department".)A high frequency of drug intake does not mean that MOH is the only headache disorder that is present [3]. Typically, the patient with MOH has an underlying primary headache disorder (eg, migraine, tension-type headache) that gradually or abruptly increased in frequency, which in turn led to an increased intake of analgesics and eventually to MOH superimposed upon the primary headache disorder. At this stage, patients may find themselves taking daily or frequent analgesics merely to prevent a disabling analgesic withdrawal headache [3].INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The Basics and Beyond the Basics. The Basics patient education pieces are written in plain language, at the 5to 6grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10to 12grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on patient info and the keyword(s) of interest.) SUMMARYRegular intake, for 15 days per month for >3 months, of simple analgesics (ie, acetaminophen, aspirin, or NSAID)Not better accounted for by another ICHD-3 diagnosis th thth thBasics topics (see "Patient information: Headache (The Basics)") Beyond the Basics topics (See "Patient information: Headache causes and diagnosis in adults (Beyond the Basics)".)Medication overuse headache (MOH) is a headache occurring on 15 or more days per month developing as a consequence of regular overuse of acute or symptomatic headache medication for more than 3 months. It usually, but not invariably, resolves after the overuse is stopped. (See 'Background' above.)The precise mechanisms that lead to MOH are still uncertain. However, multiple factors seem to play a role. These include (see 'Pathophysiology' above):Page 5of 9 Medication overuse headache: Etiology, clinical features, and diagnosis25/11/2014 http://www.uptodate.com/contents/medication-overuse-headache-etiolo...Use of UpToDate is subject to the Subscription and License Agreement. REFERENCESHeadache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia 2013; 33:629.1.Bigal ME, Rapoport AM, Sheftell FD, et al. Transformed migraine and medication overuse in a tertiary headache centre--clinical characteristics and treatment outcomes. Cephalalgia 2004; 24:483.2.Diener HC, Limmroth V. Medication-overuse headache: a worldwide problem. Lancet Neurol 2004; 3:475.3.Abrams BM. Medication overuse headaches. Med Clin North Am 2013; 97:337. 4.Lance F, Parkes C, Wilkinson M. Does analgesic abuse cause headaches de novo? Headache 1988; 28:61.5.Bahra A, Walsh M, Menon S, Goadsby PJ. Does chronic daily headache arise de novo in association with regular use of analgesics? Headache 2003; 43:179.6.Katsarava Z, Jensen R. Medication-overuse headache: where are we now? Curr Opin Neurol 2007; 20:326.7.Paemeleire K, Bahra A, Evers S, et al. Medication-overuse headache in patients with cluster headache. Neurology 2006; 67:109.8.Young WB, Silberstein SD. Hemicrania continua and symptomatic medication overuse. Headache 1993; 33:485.9.Dodick D, Freitag F. Evidence-based understanding of medication-overuse headache: clinical implications. Headache 2006; 46 Suppl 4:S202.10.Dobson CF, Tohyama Y, Diksic M, Hamel E. Effects of acute or chronic administration of anti-migraine drugs sumatriptan and zolmitriptan on serotonin synthesis in the rat brain. Cephalalgia 2004; 24:2.11.Genetic predisposition Central sensitization of trigeminal pain processing Biobehavioral factors The prevalence of MOH in the general population is approximately 1 to 2 percent, and is higher in women than in men. Migraine is the most common primary headache disorder associated with MOH. (See 'Epidemiology' above.)All acute symptomatic medications used to treat headaches have the potential for causing MOH. The risk for MOH appears to vary as follows (see 'Causal medications' above):Highest with opioids, butalbital-containing combination analgesics, and aspirin/acetaminophen/caffeine combinationsIntermediate to high with triptans Lowest with nonsteroidal antiinflammatory drugs The development of MOH is typically preceded by an episodic headache disorder, usually migraine or tension-type headache, that has been treated with frequent and excessive amounts of acute symptomatic medications. MOH often manifests as a headache that is present or develops upon awakening, and commonly occurs daily or nearly daily. (See 'Clinical features' above.)The diagnosis of MOH is based upon clinical impression. A history of analgesic use averaging more than two to three days per week in association with chronic daily headache is suggestive. The diagnosis is made when the pattern of frequent headaches fulfills the diagnostic criteria for MOH (table 1). (See 'Diagnosis' above.)Page 6of 9 Medication overuse headache: Etiology, clinical features, and diagnosis25/11/2014 http://www.uptodate.com/contents/medication-overuse-headache-etiolo...Ayzenberg I, Obermann M, Nyhuis P, et al. Central sensitization of the trigeminal and somatic nociceptive systems in medication overuse headache mainly involves cerebral supraspinal structures. Cephalalgia 2006; 26:1106.12.De Felice M, Ossipov MH, Wang R, et al. Triptan-induced latent sensitization: a possible basis for medication overuse headache. Ann Neurol 2010; 67:325.13.Fumal A, Laureys S, Di Clemente L, et al. Orbitofrontal cortex involvement in chronic analgesic-overuse headache evolving from episodic migraine. Brain 2006; 129:543.14.Boes CJ, Black DF, Dodick DW. Pathophysiology and management of transformed migraine and medication overuse headache. Semin Neurol 2006; 26:232.15.Saper JR, Hamel RL, Lake AE 3rd. Medication overuse headache (MOH) is a biobehavioural disorder. Cephalalgia 2005; 25:545.16.Zwart JA, Dyb G, Hagen K, et al. Analgesic use: a predictor of chronic pain and medication overuse headache: the Head-HUNT Study. Neurology 2003; 61:160.17.Radat F, Creac'h C, Swendsen JD, et al. Psychiatric comorbidity in the evolution from migraine to medication overuse headache. Cephalalgia 2005; 25:519.18.Fuh JL, Wang SJ, Lu SR, Juang KD. Does medication overuse headache represent a behavior of dependence? Pain 2005; 119:49.19.Pascual J, Cols R, Castillo J. Epidemiology of chronic daily headache. Curr Pain Headache Rep 2001; 5:529.20.Westergaard ML, Hansen EH, Glmer C, et al. Definitions of medication-overuse headache in population-based studies and their implications on prevalence estimates: a systematic review. Cephalalgia 2014; 34:409.21.Zwart JA, Dyb G, Hagen K, et al. Analgesic overuse among subjects with headache, neck, and low-back pain. Neurology 2004; 62:1540.22.Castillo J, Muoz P, Guitera V, Pascual J. Kaplan Award 1998. Epidemiology of chronic daily headache in the general population. Headache 1999; 39:190.23.Diener HC, Limmroth V, Katsarava Z. Medication-Overuse Headache. In: Chronic daily headache for clinicians, Goadsby PJ, Dodick DW (Eds), Decker, Hamilton 2005. p.117.24.Obermann M, Katsarava Z. Management of medication-overuse headache. Expert Rev Neurother 2007; 7:1145.25.Diener HC, Dahlof CG. Headache associated with chronic use of substances. In: The Headaches, Second ed, Olesen J, Tfelt-Hansen P, Welch KM (Eds), Lippincott, Williams & Wilkins, Philadelphia 1999. p.871.26.Atasoy HT, Unal AE, Atasoy N, et al. Low income and education levels may cause medication overuse and chronicity in migraine patients. Headache 2005; 45:25.27.Johnson JL, Hutchinson MR, Williams DB, Rolan P. Medication-overuse headache and opioid-induced hyperalgesia: A review of mechanisms, a neuroimmune hypothesis and a novel approach to treatment. Cephalalgia 2013; 33:52.28.Bigal ME, Serrano D, Buse D, et al. Acute migraine medications and evolution from episodic to chronic migraine: a longitudinal population-based study. Headache 2008; 48:1157.29.Bigal ME, Lipton RB. Excessive acute migraine medication use and migraine progression. Neurology 2008; 71:1821.30.Limmroth V, Katsarava Z, Fritsche G, et al. Features of medication overuse headache following overuse of different acute headache drugs. Neurology 2002; 59:1011.31.Krymchantowski AV. Overuse of symptomatic medications among chronic (transformed) migraine patients: profile of drug consumption. Arq Neuropsiquiatr 2003; 61:43.32.Meskunas CA, Tepper SJ, Rapoport AM, et al. Medications associated with probable medication overuse headache reported in a tertiary care headache center over a 15-year period. Headache 2006; 46:766.33.Topic 3340 Version 7.0Page 7of 9 Medication overuse headache: Etiology, clinical features, and diagnosis25/11/2014 http://www.uptodate.com/contents/medication-overuse-headache-etiolo...GRAPHICSMedication overuse headache diagnostic criteriaDescription: Headache occurring on 15 or more days per month developing as a consequence of regular overuse of acute or symptomatic headache medication (on 10 or more, or 15 or more days per month, depending on the medication) for more than 3 months. It usually, but not invariably, resolves after the overuse is stopped.A. Headache occurring on 15 or more days per month in a patient with a pre-existing headache disorder.B. Regular overuse for more than three months of one or more drugs that can be taken for acute and/or symptomatic treatment of headache:Regular intake for 10 days per month for >3 months of ergotamines, triptans, opioids, or combination analgesics, or any combination of ergotamines, triptans, simple analgesics, NSAIDs and/or opioids without overuse of any single drug or drug class alone or when the pattern of overuse cannot be reliably established.Regular intake for 15 days per month for >3 months of simple analgesics (ie, acetaminophen, aspirin, or NSAID).C. Not better accounted for by another ICHD-3 diagnosis.ICHD-3: International Classification of Headache Disorders, 3rd edition; NSAID: nonsteroidal antiinflammatory drug.Data from: Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia 2013; 33:629.Graphic 71798 Version 9.0Page 8of 9 Medication overuse headache: Etiology, clinical features, and diagnosis25/11/2014 http://www.uptodate.com/contents/medication-overuse-headache-etiolo...Disclosures: Ivan Garza, MD Nothing to disclose. Todd J Schwedt, MD, MSCI Consultant/Advisory Boards: Allergan; Zogenix; Supernus; MAP Pharmaceuticals [Migraine (OnabotulinumtoxinA, sumatriptan, topiramate ER, dihydroergotamine)]. Jerry W Swanson, MD Nothing to disclose. John F Dashe, MD, PhD Employee of UpToDate, Inc. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policyDisclosuresPage 9of 9 Medication overuse headache: Etiology, clinical features, and diagnosis25/11/2014 http://www.uptodate.com/contents/medication-overuse-headache-etiolo...