To evaluate conditioned pain modulation (CPM) in burning mouth syndrome (BMS) patients with different pain mechanisms. Twenty BMS patients (52.0 ± 6.8 years, 17 women and 3 men) and age- and gender-matched 22 healthy controls were enrolled in this randomised controlled trial. The patients received an active lingual nerve block (lidocaine) and a placebo injection (saline) randomly with an interval of 1 week in a double-blinded manner. Patients evaluated their pain intensity on a 0- to 10-cm visual analogue scale (VAS) before and after each injection, with or without CPM. Based on the anaesthesia effect, BMS patients were divided into two groups with presumed different pain mechanisms; a 'central subgroup (n = 11)' with pain relief less than 1 cm and 'peripheral subgroup (n = 9)' with pain relief more than 1 cm on the VAS. Mechanical pain threshold (MPT) and wind-up ratio (WUR) were investigated at two oral mucosa regions: the region with most intense symptoms and a control region for the patient group; tongue and buccal region for the control group. CPM was induced by immersing the left hand into cold water. A moderate level of pain (around five on the VAS) was obtained by adjusting the water temperature. MPT and WUR were measured twice for all the participants with and without CPM, which was analysed and presented as relative change in MPT and WUR. Differences between groups were analysed using two-way ANOVA. Differences within group between tests were assessed by paired t-test. At baseline, there were no significant group differences for MPT or WUR between BMS patients and healthy controls (p ≥ 0.156). The mean bath temperature to evoke moderate pain for the BMS group was significantly lower than that for the healthy control group (8.9°C vs. 11.9°C, p = 0.003). The CPM evoked an inhibitory modulation in 18.2%-44.4% of BMS patients, while for the healthy group, the ratio was 68.2%-81.8%. Central BMS patients had smaller CPM effects than healthy participants at the painful site and control site, which indicated a decreased CPM function (p ≤ 0.034). Peripheral BMS patients had lower CPM effects than healthy participants only at the painful site (p = 0.037). The present findings documented impairment of central nociceptive inhibition processing in BMS patients which was more extensive in central BMS than peripheral BMS. These findings add to the suggestion that BMS may a heterogeneous pain condition with at least two different phenotypes.
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