ORIGINAL ARTICLE Non-specific effects and clusters of women with painful TMD responders and non-responders to LLLT: double-blind randomized clinical trial Laís Valencise Magri 1,2 & Vinícius Almeida Carvalho 3 & Flávia Cássia Cabral Rodrigues 2 & César Bataglion 2 & Christie Ramos Andrade Leite-Panissi 1,3,4 Received: 14 September 2017 /Accepted: 28 November 2017 # Springer-Verlag London Ltd., part of Springer Nature 2017 Abstract The aim was to analyze the non-specific effects (placebo, spontaneous remission, and regression to the mean) of the low-level laser therapy (LLLT) in women with myofascial pain (painful temporomandibular disorder (TMD)), as well as to differentiate between responders and non-responder clusters to active and placebo LLLT according to the anxiety levels, salivary cortisol, use of oral contraceptives, and premenstrual period. Sixty-four women diagnosed with myofascial pain (Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD)) were included, divided into laser (n = 20), placebo group (n = 21), and 23 controls (without treatment (WT)). The LLLT applied was 780 nm, masseter and temporal = 5 J/cm 2 (20 mW–0.5 W/cm 2 ), and TMJ area = 7.5 J/cm 2 (30 mW–0.8 W/cm 2 ), eight sessions, twice a week. The pain intensity (visual analogue scale (VAS)), anxiety (Beck Anxiety Inventory), salivary cortisol, and menstrual cycle’ s data at the baseline, T1–T8, and 30 days after LLLT (follow-up) were evaluated. The laser group showed 80% of pain reduction, placebo 85%, and WT 43% in T8. Women with severe anxiety and at the premenstrual period did not reduce pain with any LLLT. Active and placebo LLLT had similar effectiveness during the treatment period; however, women with moderate anxiety, cortisol levels above 10 ng/ml, and without contraceptive use maintain analgesia longer with active LLLT than placebo (follow-up 30 days). Women with low levels of anxiety, salivary cortisol below 10 ng/ml, and with contraceptive use showed the higher pain reduction. The analgesia promoted by LLLT in women with myofascial pain is a result of non-specific effects during the treatment period, although active LLLT is more effective in maintaining the analgesia after treatment (30 days) for the cluster of women with moderate anxiety, salivary cortisol above 10 ng/ml, and without contraceptive use. Keywords Low-level laser therapy . Myofascial pain syndromes . Pain measurement . Placebo . Temporomandibular joint disorders Introduction Temporomandibular disorder (TMD) is a painful musculo- skeletal condition, in which the perceiving of signs and symp- toms is modulated by emotional and hormonal factors [1, 2]. Women with high levels of stress and anxiety have increased risk of developing myofascial pain, and personal traits of anx- iety are strongly associated with the diagnosis of painful TMD [3]. The hormonal fluctuations that occur in menstrual cycle seem to increase the perception of pain in the clinical context of TMD [4]. In addition to pain in the orofacial region, women with TMD often report areas of pain in other body regions. This chronic widespread pain condition is associated with pathophysiological changes in pain processing, mainly to cen- tral sensitization phenomena [5]. * Christie Ramos Andrade Leite-Panissi christie@forp.usp.br 1 Psychobiology Graduate Program, School of Philosophy, Science and Literature of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil 2 Departament of Restorative Dentistry of Dentistry School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil 3 Departament of Morphology, Physiology and Basic Pathology of Dentistry School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil 4 Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil Lasers in Medical Science https://doi.org/10.1007/s10103-017-2406-4