Phantom headache: pain-memory-emotion hypothesis for chronic daily headache?

The neurobiology of chronic pain, including chronic daily headache (CDH) is not completely understood. “Pain memory” hypothesis is one of the mechanisms for phantom limb pain. We reviewed the literature to delineate a relation of “pain memory” for the development of CDH. There is a direct relation of pain to memory. Patients with poor memory have less chance to develop “pain memory”, hence less possibility to develop chronic pain. Progressive memory impairment may lead to decline in headache prevalence. A similar relation of pain is also noted with emotional or psychiatric symptoms. Literature review suggests that there is marked overlap in the neural network of pain to that of memory and emotions. We speculate that pain, memory, and emotions are interrelated in triangular pattern, and each of these three is related to other two in bidirectional pattern, i.e., stimulation of one of these will stimulate other symptoms/networks and vice versa (triangular theory for chronic pain). Longstanding or recurrent noxious stimuli will strengthen this interrelation, and this may be responsible for chronicity of pain. Reduction of both chronic pain and psychological symptoms by cognitive behavioral therapy or psychological interventions further suggests a bidirectional interrelation between pain and emotion. Longitudinal studies are warranted on the prevalence of headache and other painful conditions in patients with progressive memory impairment to delineate the relation of pain to memory. Interrelation of headache to emotional symptoms should also be explored.     

The tension headache component of chronic daily headache

Chronic daily headache (CDH) is an overarching term that includes multiple types of frequent primary headaches that are not trigeminal-autonomic cephalgias. The components of typical CDH can be divided into a more severe or “big” headache and a less severe or “little” headache. The big headaches tend to have features of migraine while the little headaches have features of tension-type headache (TTH). Whether this represents a spectrum or continuum or whether it is the superimposition of two unique headache entities is open to debate. For subjects with big and little headache, the concept that the TTH component is part of a spectrum seems likely. Subjects with only TTH and no migrainous component seem to represent a different entity, pure chronic TTH. These patients have a daily moderate headache that is poorly responsive to current therapies and appears to be a different TTH than the migraine tension type of CDH. The TTH component of CDH may represent multiple subdivisions of TTH.     

Chronic daily headache and the revised international headache society classification

Chronic daily headache (CDH) is surprisingly common. It is best defined as a primary headache disorder with head pain on most days. There are a number of possible secondary causes of persistent headache, including traumatic, vascular, neoplastic, and infectious processes, all of which must be ruled out when the patient with frequent headache is evaluated. However, most patients with CDH seem to have a primary neurophysiologic disorder. This category of primary CDH does not seem to be a homogeneous disorder, but rather one with important subtypes. Several authors have proposed subdivisions of primary CDH such as chronic migraine, evolved migraine, transformed migraine, chronic tension-type headache, new daily persistent headache, and hemicrania continua. The International Headache Society (IHS) Classification published in 1988 did not address CDH other than to define a category “chronic tension-type headache.rd The revised IHS Classification (ICHD II) attempts to characterize CDH more thoroughly with the addition of chronic migraine and new daily persistent headache diagnoses, but this complex issue continues to defy easy categorization. This article provides a review of thinking about the nature of primary CDH and how ICHD II attempts to organize this category for much needed research purposes.     

Chronic daily headache: how to manage it?

The role of daily analgesic use (also called abuse) in chronic daily headache (CDH) for the maintenance of chronic headache is discussed. The comprehension of the underlying mechanisms of actions is lacking mainly because of the absence of animal models. The abuse should be considered as a compulsive behavior rather than linked to the type of analgesic used and related both to “how” the drug is taken and to “what” drug is used. Moreover, there is no evidence of addictive personality in these patients, and also predictive factors for the long-term outcomes are inconsistent. In the literature specific indications are lacking for the treatment to be performed in these patients. In conclusion, the main problem for these patients is to manage their headaches, and the aim of the therapy should be to enable patients to feel in control of their migraine rather than feel that migraine or analgesic drugs control them. Correspondence to L.A. Pini     

Fasting Headache

Headache is a common disorder in the general population. Fasting headache is coded to Group 10 of the second edition of the International Classification of Headache Disorders (“Headache attributed to disorder of homeostasis”). A study conducted in Denmark’s general population found a lifetime prevalence rate of 4.1% for fasting headache. Fasting headache is usually diffuse or located in the frontal region, and the pain is nonpulsating and of mild or moderate intensity. In most cases, the headache occurs after at least 16 h of fasting and resolves within 72 h after resumption of food intake. The likelihood of developing fasting headache increases directly with the duration of the fast. Headache sufferers have a higher risk of developing headache during fasting than people who do not usually suffer from headache. Hypoglycemia and caffeine withdrawal have been especially implicated as causative factors, but much remains to be understood about this topic.     

Chronic daily headache in the absence of medication overuse: Is daily or continuous pain more treatment-resistant than chronic daily headache with pain-free days?

To our patients, their families, and treatment providers who may not be headache specialists, chronic daily headache (CDH) would appear to refer to headache disorders marked by the presence of daily pain over an extended period of time. To the headache specialist, in contrast, CDH represents a family of headache disorders in which pain occurs from 15 to 30 days each month [1], now reflected in the International Headache Society (IHS) criteria for chronic migraine (CM) or chronic tension-type headache [2]. The IHS classification does not distinguish between daily CM and intermittent CM marked by at least some pain-free days [3]. Research studies and clinical reports of the diagnostic entities subsumed under CDH often include patients with pain-free days and those with true daily pain.     

Behavior during cluster headache

Cluster headache (CH), also known as “suicide headache,” is characterized by a distinctive behavior during attacks. In 80% to 90% of cases, patients are restless and constantly moving in a vain attempt to relieve pain. They often perform complex, stereotyped actions. During attacks, CH sufferers do not want to be touched, stroked, or comforted and frequently moan a great deal, cry, or even scream. They sometimes indulge in violent, self-hurting behavior. Restlessness is a highly sensitive and highly specific parameter for CH and has been included among the signs and symptoms accompanying pain of the disorder in the Second Edition of the International Classification of Headache Disorders. A few hypotheses on pathophysiology of restlessness are addressed in this paper.     

Long-term effects of a sensitisation campaign on migraine: the Casilino study

In 2003, we conducted a sensitisation campaign on migraine in the Casilino district of Rome, by sending a letter with the ID Migraine test to all the households and placing posters in the GPs’ waiting room. Out of 195 headache patients recruited, 92% had migraine while 73% had never consulted a physician for headache. The aim of this study was to evaluate the long-term impact of this campaign. The follow-up was performed by a telephone interview. The questionnaire considered the characteristics of headache, quality of life, preventive and acute treatments, drug efficacy, comorbidity and subjective usefulness of the campaign. Of the 179 migraineurs, 90.5% (mean age 40.7 ± 16.5, 139 females) were included in the follow-up. An improvement was observed in mean pain intensity (−13.9%; p < 0.0001) and mean HIT-6 score (−6.1%; p = 0.0003). The campaign was considered to be useful by 63.6% of cases, while 66.1% reported an improvement in their clinical status. Improved patients showed a decreased mean number of days with headache per month (−51.7%; p < 0.0001), pain intensity (−21.8%; p < 0.0001), headache duration (−18.1%; p = 0.0008) and HIT-6 score (−11.7%; p < 0.0001). Our data suggest that the effects of a “single shot” campaign are beneficial not only in a short-term perspective, but even in the long term. Moreover, the lack of benefit in more severe cases suggests that such patients should not be treated by GPs alone: patients in whom the HIT-6 score, frequency, severity or duration of headache worsen should be promptly referred to the headache clinic.     

Cardiac cephalgia

The purpose of this review was to provide a critical evaluation of medical literature on so-called “cardiac cephalgia” or “cardiac cephalalgia”. The 2004 International Classification of Headache Disorders codes cardiac cephalgia to 10.6 in the group of secondary headaches attributed to disorder of homoeostasis. This headache is hardly recognizable and is associated to an ischaemic cardiovascular event, of which it may be the only manifestation in 27% of cases. It usually occurs after exertion. Sometimes routine examinations, cardiac enzymes, ECG and even exercise stress test prove negative. In such cases, only a coronary angiogram can provide sufficient evidence for diagnosis. Cardiac cephalgia manifests itself without a specific pattern of clinical features: indeed, in this headache subtype there is a high variability of clinical manifestations between different patients and also within the same patient. It “mimics” sometimes a form of migraine either accompanied or not by autonomic symptoms, sometimes a form of tension-type headache; on other occasions, it exhibits characteristics that can hardly be interpreted as typical of primary headache. Pain location is highly variable. When the headache occurs as the only manifestation of an acute coronary event, the clues for suspicion are a) older age at onset, b) no past medical history of headache, c) presence of risk factors for vascular disorders and d) onset of headache under stress. Knowledge of cardiac cephalgia is scarce, due to its rare clinical occurrence and to the scant importance given to headache as a symptom concomitantly with an ischaemic cardiac event.     

Is there a therapeutic window with some antidepressants for analgesic response?

Most antidepressants and anticonvulsants used in chronic pain syndromes have dose- and concentration-response curves developed for their application to treat psychiatric disorders. Because these are important clinical tools in medication management of psychiatric syndromes, it is reasonable to expect that utilizing concentration-effect relationships and known sources of pharmacokinetic variability for determining doses for analgesia may also improve treatment tolerability and outcomes. Efforts to identify dosing “therapeutic windows” or minimum “thresholds” for analgesic efficacy have provided useful guidance for initiating treatment, reducing toxicity, and assisting with decision making in the face of limited therapeutic response. This article reviews the strengths, limitations, and potential of therapeutic drug monitoring of antidepressants and anticonvulsants as analgesics for selected chronic pain syndromes.     

Focus on therapy: hemicrania continua and new daily persistent headache

Hemicrania continua (HC) and new daily-persistent headache (NDPH) represent the only two forms of chronic daily headache in Chap. IV “Other Primary Headaches” of the second edition of the International Classification of Headache Disorders. HC and NDPH are rare and poorly defined from a pathophysiological point of view; as a consequence, their management is largely empirical. Indeed, there is a lack of prospective, controlled trials in this field, and treatment effectiveness is basically inferred from the results of sparse open-label trials, retrospective case series, clinical experience and expert opinions. In this narrative review we have summarised the information collected from an extensive analysis of the literature on the treatment of HC and NDPH in order to provide the best available and up-to-date evidence for the management of these two rare forms of primary headache. Indomethacin is the mainstay of HC management. The reported effective dose of indomethacin ranges from 50 to 300 mg/day. Gabapentin 600–3,600 mg tid, topiramate 100 mg bid, and celecoxib 200–400 mg represent the most interesting alternative choices in the patients who do not tolerate indomethacin or who have contraindications to its use. NDPH is very difficult to treat and it responds poorly only to first-line options used for migraine or tension-type headache.     

The “Other” Headaches: Primary Cough,Exertion, Sex,and Primary Stabbing Headaches

Primary cough headache, primary exertional headache, primary sexual headache, and idiopathic stabbing headache are included in “Other Primary Headaches” (Group 4) in the International Classification of Headache Disorders, 2nd edition (ICHD-II). Headaches provoked by cough, exertion, and sex have different age distributions, but they do share some clinical and pathogenic characteristics. The triggering activities frequently involve Valsalva-like maneuvers, which may explain part of the pathogenesis. Primary stabbing headache is common and characterized by ultra-short stabbing headaches. All these headache disorders respond well to indomethacin, and they are commonly comorbid with migraine except for primary cough headache. Of note, some patients with sexual headache had reversible cerebral vasoconstriction syndromes. Recent large-scaled studies have revealed that the ICHD-II criteria of these four headache disorders cannot be completely fulfilled. Further revisions for the ICHD-II criteria are required based on these results of the evidence-based studies.     

Tension-Type Headache Mimics

Tension-type headache (TTH) is a relatively featureless headache. Many primary and secondary headache disorders can mimic TTH, particularly in its chronic form, chronic tension-type headache. This review will address both primary and secondary disorders that can present with headaches phenotypically similar to TTH, and will focus on clinical pearls that help distinguish these “mimics” from TTH.     

Chronic migraine classification: current knowledge and future perspectives

In the field of so-called chronic daily headache, it is not easy for migraine that worsens progressively until it becomes daily or almost daily to find a precise and universally recognized place within the current international headache classification systems. In line with the 2006 revision of the second edition of the International Classification of Headache Disorders (ICHD-2R), the current prevailing opinion is that this headache type should be named chronic migraine (CM) and be characterized by the presence of at least 15 days of headache per month for at least 3 consecutive months, with headache having the same clinical features of migraine without aura for at least 8 of those 15 days. Based on much evidence, though, a CM with the above characteristics appears to be a heterogeneous entity and the obvious risk is that its definition may be extended to include a variety of different clinical entities. A proposal is advanced to consider CM a subtype of migraine without aura that is characterized by a high frequency of attacks (10–20 days of headache per month for at least 3 months) and is distinct from transformed migraine (TM), which in turn should be included in the classification as a complication of migraine. Therefore, CM should be removed from its current coding position in the ICHD-2 and be replaced by TM, which has more restrictive diagnostic criteria (at least 20 days of headache per month for at least 1 year, with no more than 5 consecutive days free of symptoms; same clinical features of migraine without aura for at least 10 of those 20 days).     

Headache and cognitive profile in children: a cross-sectional controlled study

We investigated whether children affected by tension-type headache and migraine without aura, compared with a healthy control group that was matched by age, culturally and socioeconomically display a diverse intellectual functioning and have a separate “cognitive profile”. A cross-sectional study was conducted from January 2006 to November 2008 at “Sapienza University” in Rome. A total of 134 children were diagnosed as being affected by either migraine without aura (93) or tension-type headache (41). On the basis of our exclusion/inclusion criteria, we enrolled 82 of these 134 children, 63 of whom were affected by migraine without aura and 19 by tension-type headache. On entry, cognitive functions were assessed in both the affected subjects and the control group by the Wechsler Intelligence Scale for Children-revised. Significant differences were found between the headache and control groups in the mean total intelligence quotient and verbal intelligence quotient scores (p < 0.001). Significant negative correlations were found between the total intelligence quotient, verbal intelligence quotient, performance intelligence quotient and the frequency of attacks (r = −0.55 and p < 0.001, r = −0.61 and p < 0.001, r = −0.29 and p < 0.01, respectively), as well as between the total intelligence quotient score and the age at headache onset (r = 0.234, p < 0.05). Our results suggest that the cognitive profile of children affected by headache should be assessed at the first child neurology outpatient observation. From a therapeutic point of view, although within a normal range, the abilities most likely to be less brilliant in such children are verbal skills.     

Back pain from the epidemiological point of view

Summary In the last decades back pain has reached dramatic proportions in industrialized countries. Disorders of the back are nowadays the leading cause of direct and indirect health care costs. Accurate prevalence estimates are needed to serve as a basis for health care evaluations. A review of epidemiologic studies in the general population reveals that back pain has reached a prevalence of 40 % for current pain. 7 to 18 % are “frequently”, “often”, “daily” or “constantly” affected. 75 % of the adult population suffers from back pain during the last year. 80 to 90 % of the adult population in industrialized countries experience back pain ever. Gender specific differences are only present in severe, chronic forms which are more often experienced by women. Back pain has a prevalence maximum at 50 to 64 years. Older persons display lower prevalence estimates. The prevalence maximum in men is one decade earlier than in women. There are several potential explanations for this prevalence pattern that are discussed in the article. Back pain can be classified by location, temporal characteristics, pain intensity and pain history. Currently, for none of these dimensions generally accepted, uniformly employed and validated definitions are available. In most of the industrialized countries back pain is one of the most expensive symptoms. 75–90 % of the direct and indirect health care costs were caused by those 5–10 % of patients who are disabled. As predictors of back pain a history of back pain and job satisfaction play by far a more important role than the extensively studied mechanical factors. For a first episode of back pain the prognosis is favorable. If the pain persist for more than three months the prognosis is unfavorable. After six months of absenteeism because of back pain more than half of the afflicted never return to work. Rarely back pain is present as a single symptom. In more than 80 % back pain is associated with pain in at least one joint. It remains to be studied if back pain may be viewed as an entity or as part of a more complex pain syndrome.      

Chronic Daily Headache in the Elderly

Disabling headache disorders are ubiquitous in all age groups, including the elderly, yet they are under-recognized, underdiagnosed and undertreated worldwide. Surveys and clinic-based research reports on headache disorders in elderly populations are extremely limited in number. Chronic daily headache (CDH) is an important and growing subtype of primary headache disorders, associated with increased burden and disruption to quality of life. CDH can be divided into two forms, based on headache duration. Common forms of primary headache disorders of long duration (>4 hours) were comprehensively defined in the third edition of the International Classification of Headache Disorders (ICHD-3 beta). These include chronic migraine, chronic tension-type headache, new daily persistent headache, and hemicrania continua. Rarer short-duration (<4 hours) forms of CDH are chronic cluster headache, chronic paroxysmal hemicrania, SUNCT, and hypnic headache. Accurate diagnosis, management, and relief of the burden of CDH in the elderly population present numerous unique challenges as the “aging world” continues to grow. In order to implement appropriate coping strategies for the elderly, it is essential to establish the correct diagnosis at each step and to exercise caution in differentiating from secondary causes, while always taking into consideration the unique needs and limitations of the aged body.     

Migralepsy,hemicrania epileptica,post-ictal headache and “ictal epileptic headache”: a proposal for terminology and classification revision

Despite the fact that migraine and epilepsy are among the commoner brain diseases and that comorbidity of these conditions is well known, only few reports of migralepsy and hemicrania epileptica (HE) have been published according to the current ICHD-II criteria. Particularly, ICHD-II describes “migraine-triggered seizure” (i.e., migralepsy) among complications of migraine at “1.5.5” (as a rare event in which a seizure happens during migrainous aura), while hemicrania epileptica (coded at “7.6.1”) and post-ictal headache (coded at “7.6.2”) are described among headaches attributed to epileptic seizure. However, to date neither the International Headache Society nor the International League against Epilepsy mention that headache/migraine may be the sole ictal epileptic manifestation. Based on the current knowledge, migralepsy is highly unlikely to exist as such. We, therefore, propose to delete this term until clear evidence its existence is provided. Moreover, we herein propose a revision of terminology and classification criteria to properly represent the migraine/headache relationships. We suggest the term “ictal epileptic headache” in cases in which headache/migraine is the sole ictal epileptic manifestation.     

Psychotropic drugs and renal failure: Translating the evidence for clinical practice

Introduction  The kidney is a primary route of drug elimination; abnormal kidney function is predicted to alter the pharmacokinetics of agents metabolized and/or excreted predominantly through this route. The high prevalence of mental disorders associated with psychotropic drug use in individuals with deteriorating renal function suggests there is a need to investigate the effects of renal failure on psychotropic pharmacokinetics. The aim of this review is to provide a clinically accessible overview of the effect of chronic renal failure on the pharmacokinetics for each of the major classes of prescribed psychotropic agents. Methods  All English language articles published between 1977 and 2008 were searched through PubMed, using the following keywords: “renal,” “kidney,” “pharmacokinetics,” “renal impairment,” “renal insufficiency,” and “renal failure.” Each of these search words was cross-referenced with the non-proprietary name of each psychotropic agent. The manufacturer’s product insert was also reviewed for some agents for updated dosing. Owing to the lack of adequately powered studies, an inclusive manner was used. Results  Chronic renal failure variably affects the pharmacokinetic parameters of psychotropic drugs. A review of each psychotropic drug is provided, with an emphasis on the individual pharmacokinetic parameters and recommended dosing. Conclusions: The adjudication of safe and effective doses for any psychotropic agent needs to be individualized. Tactics including dosage adjustment, slow titration, and careful monitoring for serious adverse events should be incorporated into practice.     

What's in a name? tension-type headache versus migraine

For years clinicians and researchers have debated the nosology of headache generally and of “migraine” versus “tension-type headache” in particular, an exhaustive process that arguably has done little to improve patient management and clinical outcome. New research data now indicate that the migraine versus tension-type distinction indeed may possess some clinical use, because patients with migraine or “mixed” headache syndromes may respond differently to a specific therapeutic intervention than patients with “pure” tension-type headache. This variable response to treatment intervention would seem to imply that similarly distinctive biologies are generating the respective headache syndromes, but to date we have insufficient evidence to support that conclusion.