Increased pain sensitivity is not a risk factor but a consequence of frequent headache: A population-based follow-up study L. Buchgreitz a, * , A.C. Lyngberg a,b , L. Bendtsen a , R. Jensen a a Danish Headache Center, Department of Neurology, Glostrup Hospital, University of Copenhagen, Nordre Ringvej, Building 23, DK-2600 Glostrup, Copenhagen, Denmark b Research Centre for Prevention and Health, Copenhagen County, Denmark Received 12 March 2007; received in revised form 17 October 2007; accepted 22 October 2007 Abstract Altered pain sensitivity is believed to play an important role for chronification of headache. It has however mainly been evaluated in highly selected patients from headache clinics and never in longitudinal studies. The present study is a 12-year follow-up of a population-based study of primary headache disorders and pain perception, combining a diagnostic headache interview with exam- ination of muscle tenderness and measurement of pressure pain thresholds in 1000 subjects drawn randomly from the general pop- ulation in Denmark. The aim of the study was to explore the cause–effect relationship between the increased pain sensitivity and the development of headache. The pressure pain thresholds were normal at baseline but had decreased at follow-up in subjects who developed chronic tension-type headache over the 12-year period (p = 0.025). In subjects who developed frequent episodic ten- sion-type headache the tenderness was normal at baseline but had increased at follow-up (p < 0.01) while the pain thresholds were normal both at baseline and at follow-up. The findings demonstrate that increased pain sensitivity is a consequence of frequent ten- sion-type headache, not a risk factor, and support that central sensitization plays an important role for the chronification of tension- type headache. Ó 2007 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. Keywords: Headache; Central sensitization; Pain sensitivity; General population; Follow-up 1. Introduction The chronic form of TTH differs from the episodic form in lack of effect of most treatment strategies, greater disability, greater use of medication and higher personal and socioeconomic costs [6]. Mechanisms caus- ing the transition from episodic to chronic TTH are therefore clinically very important for future treatment strategies. Previously, research into the mechanisms leading to tension-type headache (TTH) has focused on muscular factors. More recently, it has become clear that central factors also play an important role in the more severe forms of the disorder (for review see [6]). Based on results from clinical pain perception studies, it has been hypothesized that frequent nociceptive input from mus- cles in the cephalic region induces central sensitization and thereby increased pain sensitivity in severely affected patients [3,5,19,29,35]. This hypothesis is supported by the consistent findings of increased pericranial tender- ness in both episodic tension-type headache (ETTH) and chronic tension-type headache (CTTH) [9,21,25], but decreased pain thresholds only in CTTH [4,9,23,24,32,34]. The hypothesis predicts that increased pain sensitivity in patients with CTTH is a consequence of the disease. Pain sensitivity has, however, exclusively been evaluated in cross-sectional studies. Thus, the 0304-3959/$34.00 Ó 2007 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.pain.2007.10.023 * Corresponding author. Tel.: +45 43232796; fax: +45 43233839. E-mail address: buchgreitz@dadlnet.dk (L. Buchgreitz). www.elsevier.com/locate/pain Pain 137 (2008) 623–630