Faculty Bibliography

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.

The tricyclic antidepressant amitriptyline is the only documented and most widely used prophylactic drug for chronic tension-type headache (CTTH). However, it is not fully clarified whether the serotonin (5-HT) reuptake inhibition plays a major role for the analgesic effect of amitriptyline. To explore the importance of 5-HT reuptake inhibition for mechanism of action of the analgesic effect of amitriptyline we investigated platelet 5-HT levels during preventive treatment of CTTH with amitriptyline, the selective serotonin reuptake inhibitor citalopram, and placebo. Thirty-four patients with CTTH were given preventive treatment with amitriptyline 75 mg/day, the selective 5-HT reuptake inhibitor citalopram 20 mg/day, and placebo in a 32-week, double-blind, placebo-controlled, three-way crossover trial. Blood samples were collected in the last week of each treatment period. Platelet 5-HT was used as a measure of 5-HT reuptake inhibition and determined by high performance liquid chromatography. Area under the headache curve was 308 (157-715) (median with quartiles in parentheses) with amitriptyline and significantly lower than 377 (158-1121) with citalopram (P = 0.04) and 441 (178-1408) with placebo (P = 0.002). There was no difference between citalopram and placebo (P = 0.23). Platelet 5-HT was 0.4 (0.3-0.7) x 10(-18)mol/platelet with citalopram, which was significantly lower than 1.7 (1.2-2.4) x 10(-18)mol/platelet with amitriptyline (P < 0.001), and 3.5 (2.8-4.3) x 10(-18)mol/platelet with placebo (P < 0.001). The lower platelet 5-HT during treatment with citalopram than amitriptyline indicates that 5-HT reuptake was most effectively inhibited by citalopram. In contrast, amitriptyline was most effective in reduction of headache. This suggests that the analgesic effect of amitriptyline in CTTH is not solely due to 5-HT reuptake inhibition and that other mechanisms such as norepinephrine reuptake inhibition, NMDA receptor antagonism, blockade of muscarinic receptors and ion channels should be addressed in the future research.

Tension-type headache is a common primary headache with tremendous socioeconomic impact. Establishment of an accurate diagnosis is important before initiation of any pharmacologic therapy. Simple analgesics and nonsteroidal anti-inflammatory drugs are the mainstays of treatment of episodic tension-type headache. The tricyclic antidepressant amitriptyline is the drug of choice in the preventive treatment of chronic tension-type headache. Progress in basic neuroscience has emphasized the importance of nitric oxide inhibition and N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methylisoxasole-4-propionic acid receptor antagonism in the treatment of chronic pain. It has been demonstrated that inhibition of nitric oxide is effective in chronic tension-type headache. These interesting data indicate that more specific and effective treatment possibilities will emerge in the future.

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.