Manual therapy followed by specific active exercises versus a placebo followed by specific active exercises on the improvement of functional disability in patients with chronic non specific low back pain: a randomized controlled trial

In developed countries, 60 to 80% of the active individuals suffer from low back pain (LBP) at least once in their life[1, 2]. Generally, patients with acute episode of non specific low back pain (ALBP) recover within 6 to 8 weeks, but the recurrence is frequent, and 7 to 10% of them will experience persistent pain and disabilities for more than 3 months[2–5]. Moreover, psycho-social, physical and behavioral components play an important role in the occurrence of chronic non specific low back pain (CNSLBP). Up to now, the treatment of CNSLBP is still complex and expensive and the outcome highly unpredictable[6–8].

Several CNSLBP models have been conceptualized in order to select better appropriate conservative treatments (e.g., Biomedical Model of Health; Biopsychosocial Model of Disability[8]). O’Sullivan proposed a Classification Model[9] in which peripherally or centrally mediated back pain is the driving mechanism behind the disorder, and integrated psychological factors for their potential to amplify pain and drive disability[10]. However, no strong definite clinical results and current research evidence support this perspective.

A Cortical Dysfunction Model[11] was suggested where altered brain function plays an important role in the CNSLBP. The extent of central nervous system changes may explain the duration and severity of the condition, and be responsible for over 70-80% of the variance for intensity and duration of CNSLBP. A recent study has found a correlation between cortical changes and inappropriate response to noxious stimuli, altered body perception and psychological and cognitive manifestations[11].

Clinically, the literature still recommends active exercises as an efficient conservative treatment to reduce functional disability of CNSLBP patients[12–14]. Unfortunately, this strategy may be difficult to perform due to fear that movements would induce more pain and/or injury[15]. In fact, CNSLBP patients would tend to show signs of negative anticipation, poor pain tolerance and low level of exercise/activity achievement and outcome when asked to exercise[16–20].

The impact of manual therapy on CNSLBP has been extensively investigated but results are controversial. Randomized controlled trials reported that manual therapy is more effective on physical function, mental health, physical disability and/or pain than no intervention, sham manipulation, light exercises or general active exercises[21–25]. However, an exhaustive meta-analysis involving 39 studies did not confirm the benefit of manual therapy over active exercises on long-term pain and disability[26]. Nonetheless, some studies showed that manual therapy induces an immediate analgesic effect lasting 5 to 10 minutes after manipulation[27–32]. In addition, it may interfere with the neuromuscular, autonomic and endocrine responses, produce a placebo effect and/or alter the patient’s psychological state[33].

For these reasons, the use of spinal manipulation/mobilization is favorably recommended[34, 35]. Therefore, we postulate that a short-term positive effect on pain might facilitate the practice of subsequent active exercises and improve outcomes in CNSLBP. The aim of this study is first, to assess whether manual therapy has an immediate analgesic effect, and second, to compare the lasting effect on functional disability of manual therapy followed by active exercises to sham therapy followed by active exercises.

A total of 42 subjects were eligible for the study: 22 in the MT group, 20 in the ST group. The MT group had one patient stopping his treatment after the sixth session because of severe pain, another being unreachable for the 3-month post-treatment evaluation, and a third patient becoming unreachable for the 6-month post-treatment evaluation. For the ST group, two patients did not attend subsequent evaluations after the end of their therapeutic sessions. One had intense pain and rest was recommended by the doctor, and the other cancelled his appointment and became unreachable (Figure 1). The dropped-out rate of patients varies from 10 and 14%, ST and MT groups respectively (Tables 1 and2).

For MT/ST intervention, the immediate effect of intervention was in favor of manual therapy over detuned ultrasound. Independently from the therapeutic session and each session’s baseline measure, MT intervention showed a greater decrease in mean pain level compared to ST intervention (mean difference between interventions: -0.76 VAS units; 95% CI: -1.22 to −0.30) (Table 3; Figure 2).

Outcome	Predictors	Coeff	95% CI	P
Immediate effect on pain (base line = before each session)
VAS-pain Immediate effect	Intervention	−0.76	[−1.22;-0.30]	0.001*
	Time	0.02	[−0.03;0.06]	0.484
	Pain baseline	−0.27	[−0.33;-0.20]	<0.001
	Constant	0.81	[0.29;1.33]	0.002
Treatment effect on time (base line = before treatment)
VAS-pain Average 24 hour	Treatment	−1.24	[−2.37;-0.11]	0.032
	Time	−0.20	[−0.69;0.29]	0.426
	Pain baseline	0.43	[0.17;0.69]	0.001
	Constant	1.68	[−0.37;3.73]	0.108
ODI	Treatment	−7.14	[−12.80;-1.52]	0.013*
	Time	−1.80	[−3.92;0.33]	0.097
	ODI baseline	1.95	[1.50;2.39]	<0.001
	Constant	0.40	[−7.88;8.68]	0.924

* Statistical significance for primary outcomes (P < 0.025).

Since the time by treatment interactions were not statistically significant, the analyses were repeated after dropping the interaction terms.

Coeff = regression coefficients: same interpretation as for ordinary (least square) regression.

CI = confidence intervals; VAS-pain, Visual Analogue Scale of pain; ODI, Oswestry Disability Index.

VAS-pain (immediate effect) was the pain difference before and after each session, and time was the number of the 8 therapeutic sessions.

VAS-pain (average 24 hour) and ODI were calculated over time, i.e., before (baseline) and after the 8^th therapeutic session, as well as at 3 and 6 months after the end of the treatment.

For MT + AE/ST + AE treatment, independently from the time after treatment and from baseline measurement, a trend to a larger decrease in pain intensity (average 48-hour pain) and a statistically significantly reduced disability were observed in favor of the MT group over the ST group (VAS-pain mean group difference: -1.24; 95% CI: -2.37 to −0.30; P = 0.032, statistically not significant at the 0.025 level. ODI mean group difference: -7.14; 95% CI: -12.8 to −1.52; P = 0.013) (Table 3; Figure 3).

This study provides insufficient evidence for an effect of MT + AE on FABQ-wk, FABQ-pa or Sorensen scores (Table 4).

To the authors’ knowledge, this is the first controlled study to assess the efficacy of spinal manipulation/mobilization followed by specific active exercises. The main original result of this study is that manual therapy, immediately followed by active exercise, accelerates reduced disability in CNSLBP patients.

Several studies, with various designs, tried to assess the effect of manual therapy on CNSLBP, e.g., manual therapy alone[4, 41] or with exercises[23, 25] compared to exercises alone[23, 41] or other interventions (physician consultation with patient education; motor control exercises with cognitive-behavioral therapy; group exercises with cognitive-behavioral therapy)[4, 25]. None of these studies included a ST intervention (placebo). Therefore, the authors believe the design of the present study, with a true placebo intervention (i.e., the patient does not know that the ultrasound is ineffective), may allow to isolate the real effect of manual therapy.

Only one controlled study investigated several interventions, like for instance the effect of manual therapy (vs. placebo) and specific active exercises, with a comparable design[50]. In their study, the MT intervention involved primarily muscle energy technique, and the ST intervention consisted of placing patients in a controlled position that would potentially correct their musculoskeletal dysfunction, without having the muscle energy performed. For the group “manual therapy followed by specific active exercises”, at the end of the 6 therapeutic sessions, they observed a significant decrease in pain intensity, but not in disability, measured by the Quebec Back Pain Disability Scale (QBPDS). No long term results were collected by the authors.

Besides, this study confirms the immediate analgesic effect of manipulation/mobilization already reported in the literature[27, 28, 31]. No other studies assessed, throughout 8 consecutive therapeutic sessions, the immediate analgesic effect of manual therapy, and compared it to a “real” placebo treatment. Hemmilä et al.[22] assessed the effect of bone setting (described by the authors as gentle mobilization of the sacroiliac joint and the spinal vertebrae) on back pain to: i) light exercises and; ii) physiotherapy (massage with specific mobilizations and manual traction) during 10 one-hour therapeutic sessions over a 6-week therapy period. No significant differences were recorded between therapies at 12 months after randomization, although more patients in the bone-setting group notified their pain remained “improved”. Ferreira et al.[4] compared the effect of spinal mobilization on pain to: i) motor control exercises with cognitive-behavioral therapy and; ii) group exercises with cognitive-behavioral therapy. It showed no significant decrease at 8 weeks, 6 and 12 months compared to baseline. For both studies, no data on pain intensity were taken before and immediately after each therapeutic session, i.e., no analysis was performed to evaluate the immediate effect of manipulation/mobilization over the other therapies.

In this study, the VAS-pain scores present lower values under the MT group throughout time (i.e., before and after the 8 therapeutic sessions). However, a comparison of pain reduction between treatments (MT + AE vs. ST + AE) shows a significant difference in slopes in favor of MT group when the interaction is dropped (Table 3). This strongly suggests that the analgesic effect of MT combined with exercises can be efficient to decrease pain for CNSLBP. The reported analgesic effect of manual therapy (i.e., the immediate effect) may allow the patient to perform better/more accurate active exercises. Unfortunately, no measure of patients’ activity level was performed during and between therapeutic sessions, or after the end of the treatment. Also, it has been suggested that manual therapy may have a facilitator effect on muscle activation[33, 51]. It may also help patients to perform more accurate exercises. Both hypotheses may be supported by putative neurophysiologic mechanisms induced by manual therapy at peripheral, spinal cord and supraspinal levels[33].

These results in functional disability are quite similar to those of other studies[22, 23, 25]. Only Ferreira et al.[4] did not observe greater improvement in disability and pain for their MT group. Again, as mentioned above, the relevance of comparing groups offering fundamentally different interventions does not allow isolating the effect of manual therapy.

In the present study, the results on the FABQ questionnaire are interesting. No significant improvement in the FABQ-pa was observed (Table 4). This result appears to contradict earlier results, i.e., a good correlation between the FABQ-pa and disability (or rehabilitation outcome)[52, 53], but is in accordance with the weak association between perceived disability and fear-avoidance belief reported by Waddell et al.[46] and Sieben et al.[54]. As for the FABQ-wk, the present result is in agreement with the literature (Table 4), i.e., a low correlation between the FABQ-wk and disability[55].

There is not sufficient evidence that MT + AE has a positive influence on the static abdominal endurance, i.e. Shirado test (see Results). For unknown reasons, the patients treated with MT + AE presented a more pronounced drop of abdominal endurance than ST + AE when the treatment sessions were stopped. We cannot explain these results and further studies are clearly needed to better understand the relationship between MT, AE and abdominal endurance.

This study presents some limitations. For instance, patient recruitment was provided exclusively by the rheumatology clinic of a University hospital, which does not reflect the whole spectrum of the CNSLBP population. This may have contributed in selecting patients with more inflammatory signs and higher severity of disease. However, strict criteria of selection (e.g., CNSLBP and sick leaves from work of less than 6 months) were used in order to exclude patients with bad prognosis, e.g., severe disabilities and long-term unemployment[56]. For these reasons, the present results cannot be generalized to the CNSLBP population.

Besides, the large standard deviations obtained for the self-questionnaires and clinical tests values indicate the patients were heterogeneous. In addition, the population was smaller than the one estimated prior to study which produces statistical power problems. However, the number of subjects per group was comparable to the studies of Aure et al.[23], Rasmussen-Barr et al.[41] and Geisser et al.[50]. Despite these limitations, the authors were able to observe that, with this protocol design, manual therapy followed by active exercises was efficient on various patients with CNSLBP. Nonetheless, further studies with a larger number of patients are obviously needed in order to assess the exact role of fear avoidance in this therapy.

All data available from patients, even if they dropped out of the study, were integrated in the study analysis. Since the dropped out rate was low and similar in both treatments, no special statistical analyses were performed.

The present study confirms the immediate analgesic effect of manual therapy for CNSLBP. Followed by specific active exercises, it reduces significantly functional disability and tends to induce a larger decrease in pain intensity, compared to a control group. However, these results of our pilot study need to be confirmed by future studies with appropriate sample sizes.

Recent evidence tend to demonstrate that CNSLBP is largely characterized by structural, functional and neurochemical cortical modifications[11, 57]. In the near future, improving the knowledge of the precise neurophysiologic mechanisms of manual therapy at cortical level seems essential in order to validate the choice of this therapy for CNSLBP.