## 1 Introduction  
Osteoarthritis (OA) is considered a progressive chronic degenerative disease of the articular cartilage in the synovial joints [1] and is one of the most common types of rheumatic disease [2], affecting 303 million people worldwide [3].  
The diagnosis of knee OA is mainly based on the identification of its symptoms and is confirmed by an imaging diagnosis according to the criteria of the American College of Rheumatology (ACR) and the Kellgren and Lawrence scale [4]. However, pain phenotypes in OA patients vary considerably, and often do not correlate with the severity of radiographic findings [5]. Emerging evidence suggests that alterations in pain processing within the peripheral and/or central nervous system (CNS) may be a crucial factor in accounting for the various clinical presentations of pain related to OA [6].  
Neurophysiological, central sensitization (CS) is characterized by an increase in the afferent nociceptive information that could increase the excitability of neurons in the spinal dorsal horn [7]. This phenomenon would facilitate a possible sensitization at a central level, leading to signal amplification within the CNS, hypersensitivity to pain, and referred pain [8; 9]. Spinal cord neurons also receive information from other tissues that are far from the painful area of joint damage, such as the muscle or per-articular tendon, generating a dysfunction of the downstream inhibitory mechanisms and an increase in temporal summation (TS) and conditioned pain modulation (CPM) alterations [10; 11]. Therefore, one of the main objectives of any treatment is to improve the pain modulation systems.  
Psychosocial factors (cognitive factors, emotional factors, behavioral factors, social factors) also play a key factor in sensitizing the CNS [7]. The biopsychosocial approach in understanding the interaction between psychological and physical factors is a topic of primary importance, especially for its association with chronic pain [12]. Reducing the impact of stress and psychological factors could have a positive impact on the experience of pain, making the assessment of social, behavioral, and contextual factors necessary in pain trials.  
Manual therapy (MT) can be considered an effective treatment in the management of pain in knee OA, decreasing the pain threshold and cortical excitability. Indeed, systematic reviews support a transient pain inhibitory effect of manual therapy on psychophysical measures [13; 14]. Previous studies have investigated the reduction of pain associated with the normalization of TS and CPM variables in patients with knee OA [15; 16]. Pain mechanistic-based treatment strategies for MT give us an interesting approach for identifying patients likely to respond to MT [17]. Despite this, there is a current lack of knowledge regarding the pain mechanisms through which MT treatment induces a positive effect on musculoskeletal patients.  
The mobilization with movement technique (MwM) is a joint mobilization method based on the concurrent application of sustained mobilization applied by a therapist and an active physiological movement performed by the patient. MwM has been shown to generate hypoalgesia by stimulating the spinal dorsal horn with non-painful information. On the other hand, articular accessory mobilizations try to achieve similar effects by increasing the range of movement, reducing pain and restoring optimal kinematics between articular surfaces [18]. However, the effects of MT treatment on pain processing and endogenous pain modulation remain under investigation.  
Therefore, the main objective of this study was to investigate the influence of the MT treatment on facilitatory nociception and endogenous pain modulation in older adults with knee OA.