Characterization of migraineurs presenting interictal widespread pressure hyperalgesia identified using a tender point count: a cross-sectional study

DOI: https://doi.org/10.1186/s10194- 017- 0824- 0

Abstract-Summary Migraine is classified as a central sensitivity syndrome, typified by fibromyalgia showing widespread pressure hyperalgesia determined by a tender point.

This study was performed to examine whether: (1) there is a subgroup of epi- sodic migraineurs with widespread pressure hyperalgesia during and between attacks; (2) if such a subgroup exists, what is the prevalence and what is the differ- ence between groups with interictal widespread hyperalgesia and acute allodynia regarding the demographic and clinical characteristics of migraine.

To classify a subject’s response as widespread pressure hyperalgesia, the cutoff value for responders was defined as the positive tender point count below which 95% of controls responded.

Univariate analysis indicated that risk factors associated with interictal wide- spread pressure hyperalgesia were female gender, younger age at migraine onset, higher frequency of migraine attacks, severe headache impact, cutaneous allodynia and depression.

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Multivariate logistic regression analysis confirmed that independent risk factors associated with interictal widespread pressure hyperalgesia were female gender, higher frequency of migraine attack and younger age at onset.

Interictal widespread pressure hyperalgesia was common (42%) in the episodic migraineurs and was associated with younger age at onset, female gender, and higher frequency of headache, but not duration of migraine illness.

Presence of interictal widespread pressure hyperalgesia is assumed to be an indi-

cator of genetic susceptibility to migraine attacks.

Extended: This study was performed to examine whether: (1) a subgroup of epi- sodic migraineurs with WPH exists; (2) if such a subgroup exists, what are the dif- ferences in the demographic and clinical characteristics of migraine, including positive TP, between groups with interictal WPH and CA.

This study was approved by the institutional review board of Shinshu University

School of Medicine (approval number 3552-1).

To classify a subject’s response as WPH in a standardized manner, the cutoff value for WPH responder was defined as the TPC below which 95% of control sub- jects responded.

Background While a few studies indicated hyperalgesia to experimental pain during migraine attacks [280, 281], most studies investigated hyperalgesia between attacks [238, 241, 243, 282–288] to avoid the influence of acute allodynia.

During migraine attacks, it is difficult to evaluate hyperalgesia using a question- naire because hyperalgesia is a strong pain induced by potentially noxious stimuli and is rarely experienced in mundane activity.

A practical tool that can be used in place of QST to diagnose interictal hyperal-

gesia and CA is needed.

Palpation of these tender points (TPs) can produce a pressure pain response,

allowing examination of local and widespread hyperalgesia.

The comorbidity of migraine and FM is well known [289], and migraine is clas- sified as a central sensitivity syndrome [290–294] by typified FM showing wide- spread pressure hyperalgesia (WPH) determined by tender point count (TPC).

A common mechanism seems to underlie the widespread pressure hyperalgesia

(WPH) in both FM and migraine patients [289].

Methods Consecutive patients were considered eligible for inclusion in this study using the following inclusion criteria: episodic migraine as defined by the International Classification of Headache Disorders (ICHD)-III β criteria [11], aged 18–65 years, and subjects that had been migraine-free for at least 48 h to avoid the influence of migraine-related acute allodynia.

Although TP with mild pain was rated as positive TP in the original guidelines [295], a mild pain response was considered potentially ambiguous because the objective of this study was to evaluate the relationships between WPH and migraine characteristics.

3.3 Clinical Diagnosis

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We recruited headache-free healthy controls to define TPC cutoff values for

WPH in migraineurs.

Patients were classified into the migraine with interictal WPH subgroup, if they

had a positive TPC above the threshold.

Patients were divided into two groups according to headache-related disability:

“no severe impact” (score < 60) and “severe impact” (score ≥ 60). Results 176 episodic migraineurs (mean age  =  41.4  ±  8.0 years, 84.1% women) were enrolled in the study.

The cutoff value for WPH responder was defined as the total TPC below which

95% of control subjects responded.

As this cutoff value was 7, patients reporting TPC ≥ 7 were defined as migraineurs

with WPH.

There was no left-right difference in positive TP at paired sites in both migraineurs

and controls. (P > 0.48, Fisher’s exact test).

Kappa values were used to investigate the intra-rater agreement of the initial and

second diagnoses for positive WPH in 27 patients.

Of the 176 episodic migraineurs, interictal WPH and acute CA were observed in

74 (42%) and 115 (65.3%) patients, respectively.

Discussions Similar distributions of positive TP sites in migraine and reduced pressure pain threshold sites of FM suggested that migraine patients were consistently sensitized throughout the body with common mechanisms and factors facilitating sensitization leading to WPH in interictal migraine and FM [289].

In migraine patients, interictal WPH may be caused by dysfunction of a pain modulatory system sharing FM based on the prevalence and distribution of positive TP [296, 297].

Other factors related to the high frequencies of both interictal WPH and acute CA were female gender, younger age at migraine onset, and higher frequency of migraine attacks.

This is the first study to investigate the prevalence of interictal WPH in episodic migraineurs using TPC and demonstrating that the independent factors associated with an increased interictal WPH prevalence were female gender, higher frequency of migraine attacks, and younger age at onset.

Conclusion This non-blinded cross-sectional study investigated the prevalence of interictal WPH by TPC, using positive TP with the threshold cutoff set at ≥ moderate pain response, other than QST.

Identification of interictal WPH in migraine in daily practice using TPC is rec-

ommended to determine tailored treatment strategies.

Acknowledgement A machine generated summary based on the work of Toriyama, Toshihide; Horiuchi, Tetsuyoshi; Hongo, Kazuhiro. 2017 in The Journal of Headache and Pain.

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Characteristic differences between vestibular migraine and migraine only patients