Evidence of persistent central sensitization in chronic headaches: a multi-method study. J Headache Pain 9:295-300

Sechenov Moscow Medical Academy, Moscow, Russia.
The Journal of Headache and Pain (Impact Factor: 2.8). 11/2008; 9(5):295-300. DOI: 10.1007/s10194-008-0061-7
Source: PubMed


The aim of this study was to investigate central sensitization (CS) in chronic headaches and compare this phenomenon between chronic migraine (CM) and chronic tension-type headache (CTTH). We recruited 69 patients with chronic headaches and 18 control subjects. Questionnaires of headache history, allodynia and the Hospital Anxiety and Depression scale were administered. We recorded thresholds for pinprick and pressure pain, blink (BR) and nociceptive flexion reflex (NFR) R3 component coupled with wind-up ratios. Thresholds for pressure and pinprick pain, BR and NFR R3 were lower and wind-up ratios higher in patients. No differences of CS parameters between CM and CTTH were observed. CS is persistent and prevalent in patients with various types of chronic headache. CS levels are unrelated to the predominant side of pain, disease duration or depression. Neither is CS related to the headache type, suggesting similar mechanisms of headache chronification and chronicity maintaining and possibly explaining clinical similarity of various forms of chronic headache.

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    • "We applied a repetitive heat pain paradigm, which has been shown to activate key structures of the nociceptive system (the so-called pain matrix) in functional neuroimaging and prompted a robust habituation response over time (May et al., 2012b). Given that depressed patients (Bar et al., 2005, 2011; Terhaar et al., 2010a, 2011) and chronic pain patients (Filatova et al., 2008; Konopka et al., 2012) perceive pain different from controls, the hypothesis of the study was that the cortical computing between groups might differ. Given the chronicity of the respective conditions, we had the hypothesis that this might not be demonstrable in a single experimental pain session but would be easier to detect in standardized (Bingel et al., 2007; Doganci et al., 2011; Breimhorst et al., 2012; May et al., 2012a), repetitive pain sessions over several days. "
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    ABSTRACT: Longitudinal studies of experimental pain are rare and little is known about the differences regarding sensitization and habituation over longer periods in patients with chronic pain or depression compared with controls. We used a standardized longitudinal painful heat paradigm that was designed to induce long-term habituation in 19 patients with chronic low back pain (CLBP), 21 patients with depression (DEP) and 21 healthy participants (controls) over a time course of eight consecutive days. We applied functional magnetic resonance imaging on the first and last day of this period and after 3 months. Although the pain paradigm was standardized, patients with DEP exhibited significantly higher pain thresholds and a trend to higher pain ratings and, in functional imaging, showed less activation of the operculum and the secondary somatosensory cortex (S2) as compared to patients with CLBP and controls. Conversely, patients with CLBP showed increased activation in the anterior insula and parietal operculum as compared to patients with DEP and controls. Within session, all participants sensitized to pain, which was associated with higher activation levels in the thalamus, amygdala, midcingulate cortex, and sensory and motor areas. However, patients with depression showed significantly less activation in midbrain and brainstem areas. Given that pain and depression potentiate each other clinically, our data suggest that this may involve different cortical pain areas.
    Full-text · Article · May 2014 · European journal of pain (London, England)
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    • "A well-recognized clinical expression of central sensitization is cutaneous allodynia, which was shown to be prevalent during episodic migraine attacks at cephalic and extracephalic sites [35,36]. This phenomenon is even more evident in chronic migraine [37-39]. Based on animal models of experimental pain [40,41], some hypothesized that temporary sensitization of third-order thalamic neurons receiving convergent input from the dura, periorbital skin, and skin areas at different body sites explains the spread of cutaneous allodynia beyond the initial pain area during an attack of migraine [36,42]. "
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    ABSTRACT: Episodic migraine is characterized by decreased high-frequency somatosensory oscillations (HFOs), reflecting thalamo-cortical activity, and deficient habituation of low-frequency (LF-) somatosensory evoked potentials (SSEPs) to repetitive sensory stimulation between attacks. Here, we study conventional LF-SSEPs and HFOs in episodic migraineurs who developed chronic migraine (CM). Thirty-four episodic (15 interictally [MOii], 19 ictally [MOi]) and 19 CM patients underwent right median nerve SSEPs. The patient groups were compared to a group of 20 healthy volunteers (HV) of comparable age and gender distribution. We measured the N20-P25 LF-SSEP 1st amplitude block and habituation, and, after applying a band-pass filter (450–750 Hz), maximal peak-to-peak latency and the amplitudes of the early and late HFOs. Reduced early HFOs, lower 1st block LF-SSEPs and deficient habituation characterize MOii. Initially higher SSEP amplitudes and late normal habituation characterize both CM and MOi patients. After the digital filtration, both patient groups showed shortened latency peaks and normalization of early HFO amplitudes with increased late HFOs. When data of MO and CM patients were combined, the monthly number of days with headache negatively correlated with the LF-SSEP slope (r = −0.385, p = 0.006), which in turn negatively correlated with the 1st amplitude block (r = 0.568, p < 0.001). Our results show abnormalities in chronic migraine that are also reported during attacks in episodic migraineurs, namely early response sensitization and late habituation. The HFO analysis suggests that this sensory sensitization may be explained by an increase in the strength of the connections between the thalamus and cortex compared to episodic migraine between attacks. Whether this electro-functional behaviour is primary or secondary to daily headache, thus reflecting an electrophysiological fingerprint of the somatosensory system central sensitization process, remains to be determined.
    Full-text · Article · Sep 2013 · The Journal of Headache and Pain
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    • "Patients with frequent migraine usually evolve from episodic attacks; the possible pathogenetic explanation for this is that pain pathways become chronically sensitized from repeated episodes of headache attacks [6–8]. "
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    ABSTRACT: The aim of this study was to analyze cutaneous pain threshold (CPT) during the interictal phase in headache patients, and the relationships between headache frequency and analgesic use. A consecutive series of 98 headache patients and 26 sex- and age-balanced controls were evaluated. Acute allodynia (AA) was assessed by Jakubowski questionnaire, and interictal allodynia (IA) by a skin test with calibrated monofilaments. AA is widely known as a symptom more present in migraine than in TTH spectrum: in our study this was confirmed only in cases of episodic attacks. When headache index rises towards chronicization, the prevalence of AA increases in both headache spectrums (χ 2 13.55; p < 0.01). AA was associated with IA only in cases of chronic headache. When headache becomes chronic, mostly in presence of medication overuse, interictal CPT decreases and IA prevalence increases (χ 2 20.44; p < 0.01), with closer association than AA. In MOH patients there were no significant differences depending on the diagnosis of starting headache (migraine or tension type headache) and, in both groups, we found the overuse of analgesics plays an important role: intake of more than one daily drug dramatically reduces the CPT (p < 0.05). Thus, when acute allodynia increases frequency, worsens or appears for the first time in patients with a long-standing history of chronic headache, it could reasonably suggest that the reduction of CPT had started, without using a specific practical skin test but simply by questioning clinical headache history. In conclusion, these results indicate that the role of medication overuse is more important than chronicization in lowering CPT, and suggest that prolonged periods of medication overuse can interfere with pain perception by a reduction of the pain threshold that facilitates the onset of every new attack leading to chronicization.
    Full-text · Article · Feb 2011 · The Journal of Headache and Pain
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