Increased pain sensitivity in migraine and tension-type headache coexistent with low back pain: A cross-sectional population study.

BACKGROUND: Low back pain is common in the general population and in individuals with primary headaches. We assessed the relative frequency of self-reported back pain in persons with and without primary headaches and examined pain sensitivity. METHOD: A population of 796 individuals completed a headache interview based on ICHD criteria and provided data of interest in a self-administered questionnaire. Headache cases were classified into chronic (≥15) (CH) or episodic (<15 headache days/month) (EH). A total of 495 had a pericranial total tenderness score (TTS), and 494 had cephalic and extracephalic pressure pain thresholds (PPTs) assessed. RESULTS: Adjusted for age, gender, education and poor self-rated health, 1-year relative frequency of back pain was higher in individuals with CH (82.5%) and EH (80.1%) compared to no headache group (65.7%). In persons with back pain, TTS was higher in CH, (26.3 ± 12.1) than in EH, (18.5 ± 10.0; p < 0.001) and higher in both groups than in those with no headache, 10.8 ± 8.5 (p < 0.001 and p < 0.001, respectively). In persons with back pain, temporalis PPT were lower in CH, 169.3 ± 57.8, than in EH, 225.2 ± 98.1, and in no headache group, 244.3 ± 105.4 (p = 0.02 and p = 0.01, respectively). In persons with back pain, finger PPT were lower in CH, 237.1 ± 106.7, than in EH, 291.3 ± 141.3, or in no headache group, 304.3 ± 137.4 (p = 0.02 and p < 0.001, respectively). CONCLUSION: Back pain is highly frequent in individuals with CH, followed by EH and no headache. In persons with CH, back pain is associated with lower cephalic and extracephalic PPTs suggesting central sensitization may be a substrate or consequence of comorbidity. SIGNIFICANCE: We found that back pain has high relative frequency in individuals with CH followed EH and no headache. Back pain is associated with low cephalic and extracephalic PPTs in individuals with CH. Central sensitization may be a substrate or consequence of this comorbidity of back pain and CH.

Neuroticism, depression and pain perception in migraine and tension-type headache.

OBJECTIVES: People with migraine and tension-type headache (TTH) have psychiatric comorbidities. We aimed to test differences in mental health constructs by type and frequency of primary headache and associated pain sensitivity. MATERIALS AND METHODS: Data on headache features, neuroticism (Eysenck Personality Questionnaire) and depression (Major Depression Inventory) were obtained from 547 individuals classified into chronic (≥15) or episodic (<15 headache days/month) and into pure migraine (n=43), pure tension type headache (TTH, n=97), migraine and TTH (n=83) and no headache diagnosis (controls, n=324) groups. A pericranial total tenderness score (TTS) and pressure pain thresholds (PPTs) were measured. Differences in mental health constructs were examined by headache frequency and type using generalized linear mixed models adjusting for sociodemographic covariates. RESULTS: Depression scores were highest among people with chronic headache, lower in those with episodic headache, and lowest in controls. The chronic and episodic headache groups had higher neuroticism scores than controls. Mental health construct scores were highest for the migraine and TTH group and lowest in the control group. TTS and cephalic PPTs were correlated with neuroticism and depression and were higher in the chronic headache group compared to the no headache group even when adjusted for neuroticism and depression. CONCLUSIONS: Neuroticism and depression scores are associated with headache frequency (chronic vs episodic) and are highest for migraine and TTH followed by pure TTH then migraine. Mental health constructs were correlated with but did not influence differences in TTS and PPTs between headache groups.

Muscles and their role in episodic tension-type headache: implications for treatment.

BACKGROUND AND OBJECTIVE: Tension-type headache (TTH) imposes a heavy burden on the global population but remains incompletely understood and poorly managed. DATABASES AND DATA TREATMENT: Here, we review current knowledge of peripheral factors involved in the mechanism of TTH and make recommendations for the treatment of episodic TTH based on these. RESULTS: Peripheral activation or sensitization of myofascial nociceptors is most probably involved in the development of muscle pain and the acute episode of TTH. Repetitive episodes of muscle pain may sensitize the central nervous system resulting in progression of TTH to the chronic form. Thus, muscular factors may be responsible not only for the acute headache episode but also for chronification of the disorder. Simple analgesics and non-steroidal anti-inflammatory drugs are the mainstays of management of individual headache episodes. Ibuprofen 400 mg and aspirin 1000 mg are recommended as drugs of first choice based on treatment effect, safety profile and costs. Non-pharmacological therapies include electromyographic biofeedback, physiotherapy and muscle relaxation therapy. Future studies should aim to identify the triggers of peripheral nociception and how to avoid peripheral and central sensitization. There is a need for more effective, faster acting drugs for acute TTH. CONCLUSION: Muscular factors play an important role in episodic TTH. Ibuprofen 400 mg and aspirin 1000 mg are recommended as drugs of first choice.

Temporomandibular disorders and cutaneous allodynia are associated in individuals with migraine.

The objective of this study was to estimate and contrast the occurrence of ictal and interictal cutaneous allodynia (CA) in individuals with migraine with and without temporomandibular disorders (TMD). Both TMD and CA are common in migraine and may be associated with migraine transformation from episodic into a chronic form. Herein we hypothesize that TMD contributes to the development of CA and to more severe headaches. In a clinic-based sample of individuals with episodic migraine, the presence of TMD was assessed using the research diagnostic criteria for myofascial or mixed (myofascial and arthralgic) TMD. Ictal CA was quantified using the validated Allodynia Symptom Checklist (ASC-12). The ASC-12 measures CA over the preceding month by asking 12 questions about the frequency of allodynia symptoms during headaches. Interictal CA was assessed in the domains of heat, cold and mechanical static allodynia using quantitative sensory testing. Our sample consists of 55 individuals; 40 (73%) had TMD (23 with myofascial TMD and 17 with the mixed type). CA of any severity (as assessed by ASC-12) occurred in 40% of those without TMD (reference group), 86.9% of those with myofascial TMD (P = 0.041, RR = 3.2, 95% CI = 1.5-7.0) and in 82.3% of those with mixed TMD (P = 0.02, RR = 2.5, 95% CI = 1.2-5.3). Individuals with TMD were more likely to have moderate or severe CA associated with their headaches. Interictally (quantitative sensory testing), thresholds for heat and mechanical nociception were significantly lower in individuals with TMD. Cold nociceptive thresholds were not significantly different in migraine patients with and without TMD. TMDs were also associated with change in extra-cephalic pain thresholds. In logistical regression, TMD remained associated with CA after adjusting for aura, gender and age. TMD and CA are associated in individuals with migraine.

Cetilistat (ATL-962), a novel pancreatic lipase inhibitor, ameliorates body weight gain and improves lipid profiles in rats.

Cetilistat is a novel inhibitor of pancreatic lipase. The aim of this report is to evaluate the anti-obesity action of cetilistat in diet-induced obesity (DIO) rats. Cetilistat inhibited rat and human pancreatic lipase activity with an IC (50) of 54.8 nmol/l, and 5.95 nmol/l, respectively, meaning that it is 9.2 times more potent for human pancreatic lipase than for that of rat. Cetilistat was orally administered simultaneously with fat emulsion to Sprague-Dawley rats. Plasma triglyceride (TG) concentrations were measured before and after oral fat loading. The elevation in plasma triglyceride concentration by oral fat loading was reduced by cetilistat in a dose-dependent manner at 3, 10, 30, and 100 mg/kg, indicating that cetilistat reduces intestinal fat absorption in rats. Cetilistat was administered to DIO F344 rats as food admixture in a high-fat diet at 4.9, 14.9, or 50.7 mg/kg/day for three weeks. Both triglyceride and nonesterified fatty acid content in the feces were dose-dependently and drastically increased, suggesting the intestinal breakdown of fat and excretion. Body weight (BW) gain and white adipose tissue (WAT) weight were reduced in a dose-dependent manner. In addition, leptin, TG, and total cholesterol (TC) in plasma were reduced and there were no reports of oily stools. These results suggest that cetilistat ameliorates obesity and hyperlipidemia in DIO rats, a plausible animal model of the most common type of human obesity.

Prevalence and characteristics of allodynia in headache sufferers: a population study.

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.

Combination of low-dose mirtazapine and ibuprofen for prophylaxis of chronic tension-type headache.

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.

Generalized hyperalgesia in patients with 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.

Increased muscular and cutaneous pain sensitivity in cephalic region in patients with chronic tension-type headache.

Increased excitability of the central nervous system generated by repetitive and sustained pericranial myofascial nociception may be responsible for transformation of episodic tension-type headache into chronic form. We aimed to compare mechanical and electrical (intramuscular and cutaneous) pain thresholds in trapezius and anterior tibial regions between 20 patients with chronic tension type headache and 20 healthy controls. Pain thresholds to three types of electrical stimulation (single pulse, 2 and 100 Hz) were significantly lower in patients than in controls in trapezius muscle (P < 0.02) and in skin overlying the trapezius muscle (P < 0.05), whilst electrical pain thresholds did not differ between groups in anterior tibial muscle and skin. Quantitative sensory testing revealed increased pain sensitivity in patients as assessed by pressure-controlled manual palpation (local tenderness score, LTS; P < 0.01) and by pressure algometry (mechanical pain thresholds; P < 0.05) in test areas over the trapezius muscle, but not the anterior tibial muscle. In summary, this study demonstrates lower pain thresholds in muscle and skin of the cephalic region but not in lower limb muscle and skin in patients with chronic tension-type headache than in healthy controls. Increased sensitivity in nociceptive pathways from cephalic region may be of importance in the pathophysiology of chronic tension type headache.

Pain sensitivity in pericranial and extracranial regions.

Chronic myofascial pain is very common in the general population. The pain is most frequently located in the shoulder and neck regions, and nociceptive input from these regions may play an important role for tension-type headache. The mechanisms leading to the frequent occurrence of muscle pain in the shoulder and neck regions are largely unknown. It is possible that the pain is caused by increased sensitivity of muscle nociceptors or by central sensitization induced by nociceptive input from muscle. The primary aim of the present study was to compare muscle pain sensitivity in the trapezius and anterior tibial muscles. The secondary aim was to investigate whether temporal summation, a clinical correlate of wind-up, is more pronounced in muscle than in skin and, if so, whether such a difference is more pronounced in the trapezius than in the anterior tibial region. Sixteen healthy subjects were included. Pressure-pain thresholds and electrical cutaneous and intramuscular pain thresholds were measured at standard anatomical points in the trapezius and anterior tibial regions. Temporal summation was assessed by repetitive electrical stimulation. Pressure-pain thresholds (P = 0.005) and intramuscular electrical pain thresholds (P = 0.006) were significantly lower in trapezius than in anterior tibial muscle. Temporal summation was present in skin and muscle of both regions (P < 0.001). The degree of temporal summation was significantly higher in muscle than in skin in the trapezius region (P = 0.02), but not in the anterior tibial region (P = 0.47). In conclusion, we found that muscle pain sensitivity was higher in the trapezius than in the anterior tibial muscle. We also demonstrated that temporal summation could be induced in both muscle and skin and, importantly, that temporal summation was significantly more pronounced in muscle than in skin in the trapezius but not in the anterior tibial region. These data may help to explain why chronic muscle pain most frequently is located in the shoulder and neck regions.