## 4 Discussion  
To the best of our knowledge, this is the first study evaluating the efficacy and effectiveness of physical agent modalities in patients with CRPS-I. Although these treatments are widely available in clinical practice, scientific evidence in favor of their application for the management of CRPS-I is poor. CRPS-I is a painful and long-lasting condition that needs to be properly defined, diagnosed and treated in order to diminish its negative implications on functioning and quality of life [27]. Phenotypic and pathogenetic complexity makes it difficult to define an operational approach that is easily applicable in clinical practice. To prevent the risk of serious complications that lead to chronic pain, functional limitations and disability, a timely and appropriate pharmacological intervention should be started at the onset of symptoms. Moreover, non-pharmacological treatments, such as physical therapy and cognitive behavioral therapy, should be combined with drug therapy, and might be particularly useful in the late stages of CRPS-I, where a multimodal approach is more adequate to prevent psycho-emotional and socioeconomic implications [28]. However, evidence about the effectiveness of multimodal physiotherapy, including instrumental physiotherapy, for treating people with CRPS-I is usually lacking or unclear [29]. Our data confirm the role of physical modalities, in particular electotherapy and PEMF, as useful treatments when combined with other interventions for CRPS-I. According to international guidelines, TENS is recommended for pain treatment in patients with CRPS-I [10]. TENS reduces pain through the enhancement of the gate control mechanism [30], the promotion of brain endorphin release and the local modulation of vascular tone in injured tissues [31]. However, evidence about its role in the management of CRPS-I is still debated. There is only one RCT [24] supporting the efficacy of TENS in combination with therapeutic exercise in improving ROM and reducing pain and oedema in CRPS type I patients. According to the observational studies [20; 21; 22; 23; 25] included in our scoping review, we found data about heterogeneous populations as well as low quality of evidence. Indeed, some studies [21; 23; 25] included children and only two studies included adults [20; 22]. Starting an early TENS treatment (within 3 months from diagnosis) seems to provide best chance of recovery for children with CRPS-I [21; 23]. In the same population, TENS was administered as a single intervention following the failure of other conservative treatments [21; 23] while in adults, this approach was started after cast removal [20] or as a part of a multimodal treatment [22]. However, these empirical but anecdotal findings require confirmation in further rigorous studies. TENS is a safe and simple to use procedure to manage pain in children, but its use is contraindicated in patients with pacemakers, epilepsy, metal implants, and poor sensation. A continuous setting, between 70 and 120 Hertz and between 70 and 120 milliseconds pulse duration is recommended when TENS is used on a child for the first time [32]. Regarding TENS parameters such as frequency, pulse width, duration and numbers of sessions, used in adults with CRPS-I in the studies included, there is a large variability. A detailed treatment protocol was reported only by [PERSON] et al. [24] that demonstrated the efficacy of a daily application, for a total of 15 sessions, of TENS administered for 20 min, 100 Hertz frequency, 50-100 milliseconds pulse duration. Considering these uncertain results, future research is required to establish a standardized protocol treatment in patient with CRPS-I. One study investigated the effectiveness of scrambler therapy in patients with neuropathic pain associated to CRPS-I [26]. It has been hypothesized that this intervention interacts with C fiber surface receptors replacing pain information with synthetic \"non pain\" information [33].