Is there a brainstem generator of chronic daily headache?

Using BOLD-fMRI we have previously documented activation of the red nucleus (RN) and substantia nigra (SN) during spontaneously and visually activated migraine headache. These observations prompted us to study brainstem function in chronic daily headache patients using high-resolution magnetic resonance imaging (MRI) techniques. Seventeen chronic daily headache (CDH) patients, ten episodic migraine (EM) patients and fifteen controls (N) were imaged with a 3 tesla MRI system. For each subject, the relaxation rates R2, R2* and R2' were obtained for RN and SN. There was a significant decrease in R2' and R2* values for RN and SN in CDH compared to N and EM groups (p < 0.05), but no significant difference between the N and EM groups. A decrease in R2' and R2* indicates reduced deoxyhemoglobin and hence persistent activation of the RN and SN in CDH patients most likely secondary to ongoing headache at the time of study. The imaging data provide objective evidence of disturbed central nervous system function in CDH.     

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.     

Is there hope for chronic pain and headache?

Currently the clinical needs for pain and headache management are not met. Despite the numerous and exciting recent advances in understanding the molecular and cellular mechanisms that originate pain, we cannot yet fully explain the mechanism underlying the biology of chronic pain. Pain is a natural mechanism preserving our species survival; however, when the protective quality is lost, physiologic changes to the peripheral and central nervous systems result in the formation of chronic pain states. Once we understand how this chronic pain state is created, either through genetic, environmental, therapeutic, or other triggers we may be able to enhance our species existence, limiting maladaptive pain and suffering. The future therapeutic targets will need to address the genetics, neurophysiologic changes of the neurons and brain as well as help control immune systems including the glia. The key to successful headache and pain therapy is research aimed at prevention and minimizing the plastic changes triggering chronic pain.     

Is chronic tension-type headache a vascular headache? The relation between chronic tension-type headache and cranial hemodynamics

Twenty-seven patients with chronic tension-type headache were studied as to end-tidal PCO2, heart rate, mean blood pressure, diameter and blood flow of the common carotid arteries, cranial vascular resistance, and headache intensity at supine rest, after administration of nitroglycerin, and at head down tilt. The results were compared to the results of nitroglycerin and head down tilt provocations in age- and sex-matched controls. During supine rest, no change in chronic tension-type headache occurred. Nitroglycerin and tilting induced significant increase of the headache intensity compared to baseline in patients with chronic tension-type headache (P=0.01 and P<0.05, respectively) in contradistinction to controls who did not develop significant headache. Common carotid artery blood flow changes were similar during nitroglycerin provocations in the two groups, but greater (P<0.05) during head down tilt in patients than in controls. Lumbar cerebrospinal fluid pressure was found to be greater than 20 but less than 26 cm H2O in 45% of the 22 patients studied with chronic tension-type headache. The results indicate that the pain in chronic tension-type headache is related to cranial hemodynamics, presumably to distention of intracranial veins.     

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.     

Are there predictive factors for long-term outcome after withdrawal in drug-induced chronic daily headache?

OBJECTIVES: To investigate prognostic factors for long-term outcome of patients after inpatient withdrawal because of drug-induced chronic daily headache. PROCEDURES: Fifty-five patients (36 females) were re-examined by means of a standardized interview after inpatient withdrawal. The mean observation period was 9.28 +/- 2.85 years (mean +/- SD; median 8.58; range 5.00-13.50). RESULTS: Five years after withdrawal, one-third of the patients (34.6%) had an overall favourable outcome, one-third (32.7%) had no recurrent drug overuse and reported a clear-cut improvement of headache, and one-third (32.7%) developed recurrent drug overuse. Most relapses occurred within 2 years, and a small percentage within 5 years. No predictors for long-term outcome after inpatient withdrawal were found. CONCLUSIONS: All patients with drug-induced chronic daily headache should be considered as good candidates for inpatient withdrawal, and no patient should be excluded from that therapy.     

Is type I diabetes a virus-induced disease?

The conditions are critically reviewed under which diseases might be aetiologically related to infection by a certain virus. Such a causal correlation has to obey Koch's postulates, but may be very difficult to prove in the case of a "hit and run" process. This will be exemplified in the case of insulin-dependent diabetes mellitus (IDDM). Observations in humans and the results of experiments on laboratory animals are reported, whereby the Coxsackie B and mumps viruses are of particular interest. Furthermore, the mechanisms by which viruses may produce autoimmune diseases are discussed, including virological and immunological aspects. The hypothesis of "molecular mimicry" by Oldstone is quoted as a unifying one, allowing the combination of both aspects. His main assumption is oligopeptide homology between certain virus proteins and some cell proteins and some examples are given. In the presence of such homologies the immune system is first stimulated by the parasitic virus protein, but somewhat later this reaction switches against the host structures, causing continuing cellular damage with the development of autoimmune disease. It is concluded that Koch's postulates in such cases have to be supplemented by assaying for amino acid homologies in viruses and certain cell types.     

The patients’ perceptions of migraine and chronic daily headache: a qualitative study

This study aimed to gain insight into the management of migraine and chronic daily headache (CDH) from the patients perspective. This article outlines the patients perceptions of migraine and chronic daily headache. Thirteen semi–structured interviews were carried out with patients suffering from IHS migraine. Five patients, due to their headache frequency of more than 15 headache days per month, were classed as CDH patients. The data were transcribed verbatim and analysed in accordance with the grounded theory methodology. The main themes were: headaches, impact and headaches related to health issues. The theme headaches was sub-divided into their pain and symptoms, differentiating between their headaches and perceptions of headaches as barriers and facilitators to management. The patients perceptions of migraine and CDH were sometimes conflicting and influenced the patients management behaviours. The qualitative methodology may help to inform doctors, other healthcare professionals and headache researchers about the patients perspective and possibly develop future headache research, care and education.     

Not tonight, I have a headache?

OBJECTIVE: The present study examined the relationship between the diagnosis of migraine and self-reported sexual desire. BACKGROUND: There is evidence for a complex relationship between sexual activity and headache, particularly migraine. The current headache diagnostic criteria even distinguish between several types of primary headaches associated with sexual activity. METHODS: Members of the community or students at the Illinois Institute of Technology (N = 68) were administered the Brief Headache Diagnostic Interview and the Sexual Desire Inventory (SDI). Based on the revised diagnostic criteria established by the International Headache Society (ICHD-II), participants were placed in 1 of the 2 headache diagnostic groups: migraine (n = 23) or tension-type (n = 36). RESULTS: Migraine subjects reported higher SDI scores, and rated their own perceived level of desire higher than those suffering from tension-type headache. The presence of the symptom "headache aggravated by routine physical activity" significantly predicted an elevated SDI score. CONCLUSIONS: Migraine headaches and sexual desire both appear to be at least partially modulated by serotonin (5-HT). The metabolism of 5-HT has been shown to covary with the onset of a migraine attack, and migraineurs appear to have chronically low systemic 5-HT. As sexual desire also has been linked to serotonin levels, the results are consistent with the hypothesis that migraine and sexual desire both may be modulated by similar serotonergic phenomena.     

Does chronic daily headache arise de novo in association with regular use of analgesics?

BACKGROUND: The prevalence of chronic daily headache in association with regular use of analgesics is about 2%. Whether regular use of analgesics has a causal or consequential relationship to daily headache has not been established. A causal relationship has been suggested consequent to the observation of improvement or resolution of headache following analgesic withdrawal in patients attending headache clinics, but this observation has not been validated by controlled trials. PURPOSE: The aim of our investigation was to determine whether regular use of analgesics is associated with the development of chronic daily headache de novo and to characterize the clinical phenotype of those headaches by carefully studying chronic daily headache in patients with regular use of analgesics for a nonheadache indication. METHODS: Patients attending a rheumatology-monitoring clinic of second-line agents were interviewed by a training neurologist with regard to their analgesic and headache history. Headache classification was according to the criteria of the International Headache Society. Daily headache characteristics were surveyed via a standardized questionnaire, and headache features were further explored by a trained medical interviewer. RESULTS: Of 110 patients presenting to a rheumatology-monitoring clinic, 73% had a diagnosis of rheumatoid arthritis, 23% had seronegative arthritis, and 4% comprised a miscellaneous group. One hundred three were using one or more analgesics regularly for their arthritis. Of this group, 8 (7.6%) reported a history of chronic daily headache, each of whom reported a history of migraine. The onset of migraine occurred before the onset of chronic daily headache in 7 patients and at about the same time as the chronic daily headache in 1 patient. In those with onset of migraine prior to chronic daily headache, the mean interval before the onset of headache was 30 years (range, 10 to 50 years). Regular use of analgesics preceded the onset of daily headache in 5 patients by a mean of 5.4 years (range, 2 to 10 years). In 1 patient, analgesic use and the development of daily headache occurred at about the same time. In 1 patient, the onset of daily headache preceded regular use of analgesics by almost 30 years. Five of those with regular use of analgesics had been taking an opiate-based preparation in combination with a nonsteroidal anti-inflammatory agent in 4. Two had been on a combination of acetaminophen (paracetamol) and a nonsteroidal anti-inflammatory drug. The minimum number of tablets per week was 7, and the mean was 48 (range, 7 to 87). Of those patients who did not have daily headache, 41% had a history of migraine and 27% reported a history of tension-type headache. CONCLUSION: These findings suggest that individuals with primary headache, specifically migraine, are predisposed to developing chronic daily headache in association with regular use of analgesics.     

Post-infectious headache: a reactive headache?

Post-infectious disease syndrome includes both neurological and non-neurological disorders. However, headache as an isolated or a presenting complaint of post-infectious illness has not been well acknowledged in the literature. In this retrospective observation, patients having daily headache of more than 1 week and <4 weeks duration were included. We divided this group into patients having headache with preceding history of febrile illness in the recent past and patients without such history of febrile illness. We compared clinical features and therapeutic responses of various drugs between the groups. There were no significant differences in demographic features in these groups. However, associated neck pain, nausea, photophobia and meningeal signs were more prevalent in patients having history of preceding infection. A relatively lower proportion of subjects showed complete response to drugs at 3 months in post-infectious group. Good responses were noted to steroids in post-infectious group. In conclusion, a subset of patients with daily headache may be because of post-infectious pathology and treatment in the early stage may prevent it from becoming chronic. Large prospective studies are required to confirm these observations.     

Is childhood abuse a risk factor for chronic pain in adulthood?

Childhood sexual and physical abuse often are viewed as important factors in the development and persistence of chronic pain syndromes in adulthood. Nevertheless, earlier reviews on this issue have reached conflicting conclusions regarding the veracity of the relationship. In this critical review of existing research on childhood abuse and pain in adulthood, surprisingly mixed evidence is found, with significant effects found most consistently in very large crosssectional studies that rely on self-reported abuse status. The few prospective studies that are available do not support the relationship. When examining the literature from the perspective of epidemiological standards for inferring causation, the authors conclude that the evidence does not demonstrate a causal relationship. It appears that any overall relationship between childhood abuse and pain in adulthood probably is modest in magnitude, if it exists at all. Clinical implications and suggestions for future research directions are discussed.     

Alternative therapies in headache. Is there a role?

Alternative or complementary modes of treatment often lack scientific proof of efficacy. This is true for many drugs that are used for prophylaxis of headaches as well. Many of these complementary modes are inexpensive, harmless, and possibly effective. Patients can be given a list of options in the following order of clinician preference: aerobic exercise; isometric neck exercise; biofeedback; a combination product containing magnesium, riboflavin, and feverfew; and acupuncture. The patient must decide which of these approaches is appealing, affordable, and realistically doable.