Chronic low back pain (CLBP) stands as the leading cause of years lived with disability globally [1,2]. Addressing this widespread chronic condition poses a notable challenge to both the public and military health care systems. The effectiveness of standard management approaches for CLBP has been found to be modest in both general [3] and military/veteran [4,5] populations, further negatively impacting the quality of life of these people.

In military veterans, CLBP is the most prevalent painful condition [6,7], with prevalence rates reaching 45% [7]. Moreover, veterans are more likely to experience more severe pain intensity and pain-related disability than the civilian population [8]. The poor response to current interventions in this highly impacted population exacerbates the current opioid crisis [9], urging the need for new, effective, and noninvasive interventions.

The limited effectiveness of current interventions suggests that they may not adequately target specific mechanisms underlying CLBP. In the last few years, a paradigm shift has been noted in CLBP management, transitioning from a strictly biomedical perspective to a more comprehensive biopsychosocial approach [10]. Moreover, our understanding of the mechanisms of CLBP has evolved. For example, evidence reveals abnormal brain functioning among individuals with CLBP [11], suggesting the involvement of alterations within the central nervous system in certain people [12]. As the painful symptoms persist, a shift from circuits processing nociceptive inputs to circuits processing emotional states may occur in those at the highest risk to develop chronic pain [13,14]. The corticolimbic system (including the prefrontal cortex [PFC] and limbic system), which is critical in the regulation, processing, and control of emotions, plays a significant role in the inhibition of pain through cognitive control mechanisms within the cortex [14]. Enhanced cognitive and emotional valuation of pain may act as an amplifier of nociception [14]. This transition aligns with the identified multidimensional factors contributing to chronicity [15].

Psychological disorders like depression and anxiety and factors like pain catastrophizing, and movement pain–related fear have repeatedly been linked to the persistence of LBP and long-term disability [16,17]. These psychological factors represent higher-order cognitive and emotional processes occurring, inter alia, within the PFC [18], and alterations in brain processing may exacerbate nociception and contribute to the persistence of pain. This physiological phenomenon is referred to as nociplastic pain mechanisms [19]. Considering that psychological factors are more prevalent among veterans compared to civilians [7,20] and are associated with the emergence of chronic pain in this population [7,20-22], there might be a critical need for interventions identifying and mitigating these factors [23]. However, they are frequently overlooked in standard health care practices [24,25].

Usual physiotherapy (UP) constitutes a standard health care intervention for veterans experiencing LBP, and although being effective to improve symptoms and disability compared to no intervention, it often fails to consider the psychological prognostic factors of persistent pain. Psychologically informed practice utilizes a biopsychosocial approach to recognize and address emotional and cognitive components associated with the condition, using different therapeutic modalities such as education, gradual exposure to movement, and stress management strategies [26]. When delivered by physiotherapists combined with UP care, the psychologically informed practice is called psychologically informed physiotherapy (PiP) [26]. PiP represents a promising intervention for the management of CLBP, especially in veterans, as it targets the highly prevalent psychological factors present in this population. This approach is currently supported by evidence from civilian populations: meta-analyses have shown that integrating psychological interventions with UP leads to greater improvements in pain intensity and physical functioning in people with CLBP [27], including those presenting comorbid psychological factors [28], when compared to UP alone.

In addition to PiP, noninvasive brain stimulation over the PFC by using repetitive transcranial magnetic stimulation (rTMS) may be useful to modulate the cognitive and emotional processing involved in pain mechanisms [29,30]. This approach is supported by large randomized controlled trials in psychiatric populations [29]. rTMS depolarizes neurons under the stimulating coil, and modulates brain excitability [31], leading to changes in network connectivity [29] that have been linked to reductions in symptoms such as rumination and negative bias [29,31]. Through potential similar mechanisms, rTMS over the PFC has been shown to reduce pain intensity in cases of neuropathic pain [32], a finding that may relate to the high prevalence of psychological comorbidities among people with chronic pain [16,17]. To date, most studies that have investigated the use of rTMS for chronic musculoskeletal pain stimulated the motor cortex (M1), yielding conflicting results [33-35]. Stimulating the PFC could optimize results by targeting brain areas specifically involved in pain modulation. A pilot randomized controlled trial (RCT) (n=20) studied the efficacy of noninvasive brain stimulation over a prefrontal cortical area in veterans with CLBP, and this stimulation resulted in a large improvement in the physical functioning and depressive symptoms compared to a placebo [36]. PiP and rTMS are two promising interventions specifically targeting psychological factors and cortical mechanisms contributing to CLBP in veterans. Despite these promising pilot results, good quality RCTs investigating the effectiveness of rTMS over the PFC for chronic LBP are still needed.

PiP and rTMS are two promising interventions specifically targeting psychological factors and cortical mechanisms contributing to CLBP in veterans. Combining psychologically informed clinical intervention to rTMS could enhance treatment outcomes, as they could both modulate cognitive and emotional processing involved in pain mechanisms, through different pathways [29]. However, the combination of these two interventions has never been studied in chronic musculoskeletal pain and compared to usual care.

Therefore, the main objective of this study will be to compare the effectiveness of (1) combining PiP + active rTMS, (2) PiP + sham rTMS, and (3) UP alone in improving the physical functioning in veterans experiencing CLBP and comorbid psychological factors. The secondary objectives will be to compare their effectiveness on pain intensity, quality of life, movement pain–related fear, pain catastrophizing, self-efficacy, depressive symptoms, medication use, and posttraumatic stress disorder symptoms. We hypothesize that the combination of active rTMS + PiP will result in a larger effect on primary and secondary outcomes compared to PiP + sham rTMS and UP alone. In addition, we hypothesize that PiP with active rTMS or sham rTMS will be more effective than UP.

Ethics approval was obtained in January 2025, and participating physiotherapists completed the 2-day PiP training in May 2025. Participants have been recruited since June 2025. As of December 2025, 28 participants have been included, and recruitment is expected to continue up to June 2027, targeting the inclusion of approximately 4 new participants per month. Follow-up should be completed by December 2027, and results will be analyzed. The results of this randomized controlled trial should be published and available in June 2028.

This study will investigate the effectiveness of combining psychologically informed physiotherapy and rTMS over the dorsolateral PFC for veterans with CLBP. The management of veterans with CLBP is challenging. Although LBP is the most prevalent source of chronic pain, only modest therapeutic effects are observed [4,5]. Furthermore, veterans with CLBP experience more severe pain and limitations than civilians and are more likely to be prescribed opioids, increasing the risk of chronic opioid use, overdose, and death [9,56]. Identifying innovative, effective, and noninvasive interventions for the management of CLBP in this population is paramount.

The presence of psychological factors such as anxiety, depression, and stress disorders has been frequently observed in veterans living with chronic pain, and growing evidence suggest that these factors contribute to the persistence and intensity of symptoms [7,20-22]. Therefore, targeting the emotional and cognitive factors of pain with PiP and rTMS interventions might be a solution to further improve the quality of life of these people.

Evidence for the effectiveness of rTMS over PFC in chronic musculoskeletal pain is sparse [57], with previous studies mostly targeting M1 and yielding conflicting results [34,35]. Targeting the dorsolateral PFC could be more effective than M1, as the left dorsolateral PFC is involved in cognition and emotion processing that may negatively influence recovery in patients with chronic pain [31,39]. This is also supported by previous studies yielding promising results on the effectiveness of rTMS over the left dorsolateral PFC for neuropathic pain [41].

Various types of psychotherapy (eg, cognitive behavioral therapy, acceptance and commitment therapy, mindfulness-based approaches), when combined with physiotherapy, have been associated with greater improvements in pain intensity and physical functioning among individuals with CLBP, compared to usual care [27]. Moreover, psychologically informed interventions have shown particularly promising results in the treatment of CLBP among patients presenting comorbid psychological factors [28]. Thus, combining these two approaches could enhance treatment response in veterans with CLBP, a population with a high prevalence of psychological disorders. One possible explanation would be that they both target cognitive and emotional mechanisms involved in pain processing but through different pathways [29]. The hypothesis for an enhanced response when combining the two approaches is supported by previous research conducted in patients with major depression. For example, the combination of cognitive behavioral therapy and rTMS treatment yields greater improvements in symptoms and remission rates than previous RCTs evaluating these treatment modalities alone [29].

This study will address some of the top priorities in the management of LBP, that is, to prioritize noninvasive and nonpharmacological biopsychosocial intervention, as recommended by both civilian [58,59] and veteran [60] guidelines. More specifically, it will provide new evidence on the effectiveness of two innovative interventions little studied to date in veterans with CLBP (ie, PiP and rTMS). Furthermore, while the body of evidence supporting the efficacy of rTMS in treating mental health disorders such as major depression or posttraumatic stress disorders is steadily growing [61], important gaps remain in our understanding of its application among patients experiencing chronic musculoskeletal pain, particularly those presenting psychological risk factors. Should our hypotheses be confirmed and PiP demonstrates superior outcomes compared to UP, the findings of this study could yield substantive clinical implications. For example, such results could motivate clinicians to acquire training in administering PiP, as this training can be easily adapted across various health care professions.

Some limitations should, however, be mentioned. First, the optimal parameters for rTMS treatment over the PFC are still unknown. The parameters for this study are based on available evidence, which has mainly been conducted in patients with neuropathic pain [62-64]. It is possible that they are not optimal for the treatment of CLBP. Second, based on evidence from the population with depression, the use of psychotropic medication may attenuate the treatment response to rTMS [65]. We anticipate a high prevalence of psychotropic medication use among our participants, given the elevated rates of psychological disorders observed in veteran populations [7,20]. Finally, several clinicians will be providing care for whom PiP is a new concept. As such, it is possible that the standardization of the PiP intervention may be suboptimal despite the two days of training provided. To optimize standardization and application of the concepts, clinicians will be able to contact the expert clinician who provided the training throughout the study to validate information about the intervention provided. In addition, clinicians’ logbooks will allow us to see which interventions were used with participants.