Faculty Bibliography

OBJECTIVE: The authors estimated the prevalence and severity of cutaneous allodynia (CA) in individuals with primary headaches from the general population. METHODS: We mailed questionnaires to a random sample of 24,000 headache sufferers previously identified from the population. The questionnaire included the validated Allodynia Symptom Checklist (ASC) as well as measures of headache features, disability, and comorbidities. We modeled allodynia as an outcome using headache diagnosis, frequency and severity of headaches, and disability as predictor variables in logistic regression. Covariates included demographic variables, comorbidities, use of preventive medication, and use of opioids. RESULTS: Complete surveys were returned by 16,573 individuals. The prevalence of CA of any severity (ASC score >or=3) varied with headache type. Prevalence was significantly higher in transformed migraine (TM, 68.3%) than in episodic migraine (63.2%, p < 0.01) and significantly elevated in both of these groups compared with probable migraine (42.6%), other chronic daily headaches (36.8%), and severe episodic tension-type headache (36.7%). The prevalence of severe CA (ASC score >or=9) was also highest in TM (28.5%) followed by migraine (20.4%), probable migraine (12.3%), other chronic daily headaches (6.2%), and severe episodic tension-type headache (5.1%). In the migraine and TM groups, prevalence of CA was higher in women and increased with disability score. Among migraineurs, CA increased with headache frequency and body mass index. In all groups, ASC scores were higher in individuals with major depression. CONCLUSIONS: Cutaneous allodynia (CA) is more common and more severe in transformed migraine and migraine than in other primary headaches. Among migraineurs, CA is associated with female sex, headache frequency, increased body mass index, disability, and depression.

OBJECTIVE: To develop and validate a questionnaire for assessing cutaneous allodynia (CA), and to estimate the prevalence and severity of CA in the migraine population. METHODS: Migraineurs (n = 11,388) completed the Allodynia Symptom Checklist, assessing the frequency of allodynia symptoms during headache. Response options were never (0), rarely (0), less than 50% of the time (1), > or = 50% of the time (2), and none (0). We used item response theory to explore how well each item discriminated CA. The relations of CA to headache features were examined. RESULTS: All 12 questions had excellent item properties. The greatest discrimination occurred with CA during "taking a shower" (discrimination = 2.54), wearing a necklace (2.39) or ring (2.31), and exposure to heat (2.1) or cold (2.0). The factor analysis demonstrated three factors: thermal, mechanical static, and mechanical dynamic. Based on the psychometrics, we developed a scale distinguishing no CA (scores 0-2), mild (3-5), moderate (6-8), and severe (> or = 9). The prevalence of allodynia among migraineurs was 63.2%. Severe CA occurred in 20.4% of migraineurs. CA was associated with migraine defining features (eg, unilateral pain: odds ratio, 2.3; 95% confidence interval, 2.0-2.4; throbbing pain: odds ratio, 2.3; 95% confidence interval, 2.1-2.6; nausea: odds ratio, 2.3; 95% confidence interval, 2.1-2.6), as well as illness duration, attack frequency, and disability. INTERPRETATION: The Allodynia Symptom Checklist measures overall allodynia and subtypes. CA affects 63% of migraineurs in the population and is associated with frequency, severity, disability, and associated symptoms of migraine. CA maps onto migraine biology.

The treatment of chronic daily headaches should focus not only on establishing an effective plan for pain therapy but also on addressing factors that may diminish progression from episodic headache toward chronic daily headache. These measures may translate into better treatment efficacy and satisfaction, as well as decrease the headache burden. Because episodic migraine progresses to chronic daily headache in some (not most) individuals, research will increasingly focus on identifying factors associated with progression, such as specific genetic and environmental risk factors, including comorbidities. Ultimately, the assessment of the migraine patient will include an evaluation of risk factors for progression. In addition to the symptom profile, evaluation will increasingly focus on comorbidities, ictal and interictal functional consequences of migraine, health-related quality of life, treatment needs, and treatment preferences. Estimation of the risk of progression will incorporate assessments of comorbidity, exposures, and eventually biomarkers. Those with high risk of progression will be more aggressively treated, not just to relieve current pain and disability but to prevent progression. Therefore, treatment will focus on decreasing current burden and preventing future burden.

Chronic headaches are difficult to treat and represent the biggest challenge in headache centres. Mirtazapine has a prophylactic and ibuprofen an acute effect in tension-type headache. Combination therapy may increase efficacy and lower side effects. We aimed to evaluate the prophylactic effect of a combination of low-dose mirtazapine and ibuprofen in chronic tension-type headache. Ninety-three patients were included in the double-blind, placebo-controlled, parallel trial. Following a 4-week run-in period they were randomized to four groups for treatment with a combination of mirtazapine 4.5 mg and ibuprofen 400 mg, placebo, mirtazapine 4.5 mg or ibuprofen 400 mg daily for 8 weeks. Eighty-four patients completed the study. The primary efficacy parameter, change in area under the headache curve from run-in to the last 4 weeks of treatment, did not differ between combination therapy (190) and placebo (219), P = 0.85. Explanatory analyses revealed worsening of headache already in the third week of treatment with ibuprofen alone. In conclusion, the combination of low-dose mirtazapine and ibuprofen is not effective for the treatment of chronic tension-type headache. Moreover, the study suggests that daily intake of ibuprofen worsens headache already after few weeks in chronic tension-type headache.

Increased pain sensitivity in the central nervous system may play an important role in the pathophysiology of chronic tension-type headache (CTTH). Previous studies using pain thresholds as a measure of central pain sensitivity have yielded inconsistent results and only a few studies have examined perception of muscle pain without involvement of adjacent tissues. It has been suggested that suprathreshold testing might be more sensitive than threshold measurements in evaluation of central hyperexcitability in CTTH. The aim of the study was to compare pain ratings to suprathreshold single and repetitive (2 Hz) electrical stimulation of muscle and skin in cephalic (temporal and trapezius) and extracephalic (anterior tibial) regions between patients with CTTH and healthy subjects. In addition, we aimed to examine gender differences in pain ratings to suprathreshold stimulation and degree of temporal summation of pain between patients and controls. Pain ratings to both single and repetitive suprathreshold stimulation were higher in patients than in controls in both skin and muscle in all examined cephalic and extracephalic regions (P < 0.04). Pain ratings to both single and repetitive suprathreshold electrical stimulation were significantly higher in female compared with male patients (P < 0.001) and in female compared with male controls (P < or = 0.001). The degree of temporal summation of muscular and cutaneous pain tended to be higher in patients than in controls but the differences were not statistically different. This study provides evidence for generalized increased pain sensitivity in CTTH and strongly suggests that pain processing in the central nervous system is abnormal in this disorder. Furthermore, it indicates that suprathreshold stimulation is more sensitive than recording of pain thresholds for evaluation of generalized pain perception.

Frequent use of symptomatic headache drugs may induce medication overuse headache. In primary care settings, medication overuse headache is the third common diagnosis of headache, next to migraine and tension-type headache. The pathophysiologic mechanisms are unknown. It is a severely disabling condition that has a huge economic impact on society. Treatment includes complete drug withdrawal, and the prognosis is good. Preventive measures and providing information to the patients are very important.

Tension-type headache is one of the most common primary headache disorders. Advances in basic pain and clinical research have improved our understanding of pathophysiologic mechanisms of tension-type headache. Increased excitability of the central nervous system generated by repetitive and sustained pericranial myofascial input may be responsible for the transformation of episodic tension-type headache into the chronic form. Studies of nitric oxide (NO) mechanisms suggest that NO may play a key role in the pathophysiology of tension-type headache and that the antinociceptive effect of nitric oxide synthase inhibitors may become a novel principle in the future treatment of chronic headache. Future studies should focus on investigation of the source of peripheral nociception, the role of descending pain modulation, and the development of an animal model of tension-type headache to support the pathophysiologic importance of central sensitization in tension-type headache.