Healthy Men
Kesava Kovanur Sampath, PT, MOst1
Erik Botnmark, PT1
Ramakrishnan Mani, PT, PhD1
James David Cotter, PhD
Rajesh Katare, PhD
Pujika Emani Munasinghe, BSc
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The study protocol was approved by the University of Otago Human Ethics
Committee (H14/150), Dunedin, New Zealand. The study was funded by a grant
from the New Zealand Manipulative Physiotherapist Association (NZMPA). The
authors declare that they have no affiliations with or financial involvement in any
organization or entity with a direct financial interest in the subject matter or materials
discussed in the article.
We sincerely thank Dr Andrew Gray for his expert statistical advice for this project.
Journal of Orthopaedic & Sports Physical Therapy
2 Abstract
5 involving multiple systems including the sympathetic nervous system (SNS) and the
12 Methods: Twenty four healthy males aged between 18 and 45 years were
13 randomized into two groups: thoracic spinal manipulation (n=12) and sham (n=12).
14 Outcome measures were salivary cortisol (g/dL), salivary testosterone (pg/mL), T/C
15 ratio, HRV and changes in oxy-haemoglobin (O2Hb) concentration of the right calf
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16 muscle (mol/L). Measurements were done before and at 5 minutes, 30 minutes and
18 Results: A statistically significant group by time interaction was noted for T/C ratio
20 differences were noted for salivary cortisol concentration at 5 min (mean difference
21 (MD), 0.35; 95% CI: 0.12to0.6; interaction: p < .001) and T/C ratio at 6 hours post-
22 intervention (MD), -0.91; 95% CI: -1.69to-0.04, p < 0.05). However, SM did not
24 group.
1
25 Conclusion: Thoracic SM resulted in an immediate decrease in salivary cortisol
30
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31
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2
32 Spinal manipulation (SM) is a specific hands-on approach commonly used by
33 several different therapeutic professions to treat spinal pain4,35. Though the exact
34 mechanism through which SM operates are still unclear4; various mechanisms have
41 the use of Near Infrared Spectroscopy (NIRS)12,26,37. This method uses light in the
42 near infrared spectrum (600 1000 nm) from an optode attached to the skin.
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44 deoxygenated (HHb) hemoglobin and changes in the absorption of light can be used
45 to calculate changes in levels of O2Hb and HHb27,36. This in turn can be used to
47 autonomic regulation of skeletal muscle blood flow is dominated by the SNS 29,56,
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51 parasympathetic nervous system (PNS)20; therefore the interplay between these two
52 systems effects how the tissues respond to stress/damage. Heart rate variability
55 three oscillatory components in the spectral profile: (a) a very low-frequency (VLF)
56 band (< 0.04 Hz); (b) a low-frequency (LF) band (0.04 to 0.15 Hz) and (c) a high-
3
57 frequency (HF) band (0.15 to 0.4 Hz)55,82. While the HF component is related to the
58 PNS efferent activity, the LF component corresponds to both SNS and PNS efferent
60 autonomic neural activity55. The use of LF/HF ratio has been criticized32,45 as it
61 oversimplifies the complex non-linear interactions between the SNS and the PNS
62 divisions of the ANS5. Despite this, the LF/HF ratio still remains a widely used tool to
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65 and Polus (2006) reported that a thoracic SM resulted in changes in HRV, Ward et
66 al. (2012) did not report any changes in ANS function following a thoracic SM.
68 sampling as a non-invasive tool for the measurement of free cortisol and thereby the
69 HPA axis activity has been well established46. Being a hormone, cortisol has a
71 including timing of sampling; number and nature of study days; day of data collection
72 (weekend vs. week days); drinking habits (Example: coffee and alcohol); eating
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73 habits (food with high sugar content); dental hygiene/tooth brushing; smoking; and
75 these factors is crucial for reliably measuring changes in cortisol before and after an
77 studies that have investigated the effects of SM on the HPA axis64,66,90 making it
4
82 and the HPA axis are known to interact with testosterone and cortisol mutually
83 inhibiting each other3,52. The balance between testosterone and cortisol (T/C ratio)
85 activity28 and has been used as a hormonal biomarker to determine over training in
91 axis)15. It has been shown that SM results in rapid hypoalgesia with concurrent SNS
95 to SM (i.e., SNS-HP axis) in the same trial. Moreover, studies have only explored
96 immediate changes (30 minutes to 2 hours) in the HPA axis activity. Therefore,
100 vasoconstriction (reduced O2Hb) of skeletal muscle in the calf measured by NIRS.
102 whether changes in the SNS activity are accompanied by changes in the HP axis
103 activity (T/C ratio). This may provide important mechanistic information that could be
104 of interest to physical therapists for two important reasons: (1) it has been well
105 established that the neuroendocrine mechanisms (HPA-SNS) play a crucial role in
106 the modulation of pain and inflammation15. Hence, neuroendocrine response can be
5
107 a potential mechanism of pain inhibition and tissue healing following SM (2) As
109 these techniques by health care providers. Therefore, the objectives(s) of this
110 randomized controlled trial (RCT) were to determine the short-term changes in SNS
111 activity (using NIRS); SNS/PNS balance (using HRV); changes in cortisol,
115 This was a randomised controlled trial using a repeated measures study
116 design. The ethical approval for this study was obtained from the University Human
117 Ethics Committee. All participants signed an informed consent prior to participation in
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119 Participants
120
121 Participants were recruited from the wider community through flyers, posters
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122 and e-mail. Healthy males between 18 and 45 years of age with no history of
123 significant pain or illness were eligible to participate in the study. Exclusion criteria
124 were: history of serious pathologic or psychiatric disorder; previous spinal (or other
125 relevant) surgery; any bone weakness or thoracic spine conditions such as
130 a computer generated random numbers table69. Participants were then block
6
131 randomized to either the intervention (SM) group or a sham intervention group. This
132 was done by the use of sealed opaque envelopes. A research assistant not
133 otherwise involved in the study did initial screening and randomisation. This ensured
134 that group allocation was concealed, and that the outcome assessor and the
135 participant were blinded. However, due to the nature of the intervention blinding of
136 the manual therapist delivering the intervention was not possible.
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137 Procedure
138
140 assistant not otherwise involved in the study. Participants who met the inclusion
141 criteria were given salivary collection devices, an instruction sheet about saliva
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142 collection and the perceived stress scale (PSS-10)17. The PSS-10 is a self-reported
143 instrument with high reliability and validity designed to measure ones level of
144 perceived stress and has been widely used in research78. The PSS-10 was used in
145 this study as perceived stress is known to influence both the HPA axis and the ANS
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146 activity15,17. Scores of 20 or higher are considered high stress. The participants were
147 also given a sheet to self-report (a) number of hours slept during the two days of
148 data collection (b) time of saliva sample collection and (c) any alcohol or medication
150 The RCT took place in a laboratory where lighting, temperature and humidity
151 (24C, 40%) were kept constant as environmental factors have been shown to
152 influence HRV recordings42. Upon arrival, the participants height and weight were
153 recorded and any contra-indications for SM were screened. Participants returned the
154 completed PSS-10 scale and were given a 5-minute rest period following which pre-
7
155 intervention salivary samples (B2) were collected. The participant lay supine upon a
156 treatment plinth with their legs extended. During the data recording, participants
157 were asked to lie down as still as possible to avoid interference with data recording 79.
159
160 Saliva sample were collected via unstimulated passive drool as cotton based
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161 sampling devices may introduce bias into the measurement75. The time of saliva
162 sample collection was standardised in a way that participants collected saliva at
163 approximately the same time on day-1 and day-2. For complete collection procedure
165 Intervention
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166
167 The participant was asked to cross the arms in front of the body placing each
168 hand on the opposite shoulder so that elbows were on top of each other in front of
169 the lower chest (figure 1). The physical therapist then rolled the participant over on
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170 their side and placed the fixating hand, curled into a fist with the thumb and index
171 finger extended (commonly called the pistol grip)18, at the level of the fifth thoracic
172 vertebra, an area known to contain preganglionic neurons of the SNS 8,34,87. The
173 therapist then rolled the participant back to the supine position. High velocity low
174 amplitude thrust was delivered through the participants upper extremity and thorax
175 upon expiration18. A single thrust was used to standardise the intervention.
176 For the sham intervention the same setup was used, but the therapist did not
177 place a fixating hand against the thoracic spine and no thrust was given. Both the
8
179 *********INSERT FIGURE 1 HERE*************************
181
183
184 Salivary cortisol and testosterone have been shown to be a valid and reliable
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185 surrogate measures of the activities of the HPA and HPG axes respectively23,40.
188
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189 NIRS has been shown to demonstrate high degree of validity and intra-subject
190 reproducibility51. The standard error of measurement for O2Hb in skeletal muscle by
191 NIRS was calculated at 8.53%51. For this study, the point of largest circumference of
192 the right calf was identified and measured. The NIRS-optode was placed one third of
193 this distance medially from the anterior border of the tibia along the line of largest
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194 circumference. This placed the optode over the medial belly of gastrocnemius, which
195 has previously been shown to be a reliable placement of a NRIS optode 79 (figure 1).
196 The leg was supported on pillows under the knee and ankle to just suspend the
197 NIRS-optode from the table to eliminate any movement of the optode in relation to
198 the skin. The NIRS-optode was held in place by double sided adhesive tape, and an
199 elastic bandage was loosely wrapped around the calf to eliminate disturbances from
202
9
203 For changes in HRV, the LF/HF ratio was the outcome measure as this has
204 been suggested to best represent changes in autonomic activity82. HRV was
205 recorded using single use disposable electrodes (Blue Sensor SP, Ambu,
206 Denmark), and a lead 2 ECG setup was used. The ECG signal was fed through a
209
210 Data were recorded using LabChart 8 (ADInstuments, Dunedin, New Zealand,
211 www.adinstruments.com). NIRS and ECG data were continuously recorded from 5
213 collected at 8 different time points on two consecutive week days to reduce the
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214 within subject variation of situational factors such as daily schedules15. On day 1,
215 participants collected baseline salivary samples at home on 3 different time points
216 (morning (AM) afternoon and night (PM)). On day 2, salivary samples were collected
218 points (P1- 5 minutes, P2 30 minutes and P3 night (PM), approximately 6 hours
222
223 For NIRS data, mean 30s blocks of OHB before intervention were calculated,
224 as this has have been recommended to achieve accurate readings36. This was set to
225 zero, as the equipment used in this study calculates change from baseline. Change
226 scores from baseline were then calculated immediately at 1 minute, 5 minutes and
10
227 30 minutes after the intervention. For HRV data, 5 minutes before, 5 minutes and 30-
228 minutes after the intervention were analysed, as analysis of 5 minute blocks is
231
232 The level of testosterone and cortisol in all the test samples were measured
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233 using commercially available ELISA kit (Salimetrics, USA) according to the
237
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239 which are currently unknown), cortisol was considered primary. From previous
240 literature13,64,66,90, an effect size of 0.25 was considered practical in studies involving
241 measuring cortisol in normal individuals. Based on the repeated measures mixed
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242 design of the current study, a power calculation was performed using G power
243 (version 3.0.1.0). A sample size of n = 24 was required to provide 80% power at the
246
247 Data for continuous variables were expressed as mean SD. Raw cortisol
248 values were log transformed to address non-normality and skewness43. Any outliers
249 were handled by winsorising the data point54. The Shapiro-Wilk and Levene tests
250 were performed to assess normality and homoscedasticity67. A two-way mixed model
11
251 with absolute agreement was used to calculate the intra-class correlation coefficient
252 (ICC (3, 1)) for the inter-day reliability (day 1 and day 2) of morning and afternoon
253 salivary cortisol and testosterone values. An ICC 0.20 was defined as poor, an ICC
254 between 0.21 to 0.40 was defined as fair, an ICC between 0.41 and 0.60 was
255 defined as satisfactory, an ICC between 0.61 and 0.80 was defined as good, and an
256 ICC 0.81 was defined as an excellent agreement between both evaluations 88. A
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257 repeated measures analysis of variance (RM-ANOVA) was performed to test the
258 effect of the between-group factor (sham or SM) and within group factor (time) on the
259 dependant variables (salivary cortisol, salivary testosterone, T/C ratio, HRV and
260 OHB)67. The hypothesis of interest was the group-by-time interaction. A post-hoc
261 pairwise comparison between groups at different time points was also carried out. A
262 Bonferroni correction was used for adjusting for multiple post hoc comparisons 1.
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263 Eta-square was used for measuring effect sizes. Management and analysis of data
264 were performed using the statistical package SPSS for windows version 22.0 (SPSS
265 Inc, Chicago, IL). The level of statistical significance was set at p<0.05.
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266 RESULTS
267
268 The flow of participants is shown in figure 3. The data collection for the study
269 happened between March and June 2015. The data collection was stopped after the
270 24th participant as no loss to follow-up was anticipated given the one-off nature of the
271 intervention.
273 There was no missing data. Participants did not vary in baseline
274 characteristics, expect for height (table 1). No difference was found in the number of
12
275 hours slept during the two days of data collection; alcohol or medication usage
278 The ICC calculated between day 1 and day 2 for salivary cortisol samples
279 indicated strong agreement (0.71) between the morning measures; a satisfactory
280 agreement (0.47) between the afternoon measures. The ICC calculated for salivary
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281 testosterone indicated a fair agreement (0.4) between the morning measures; and a
284 There was a statistically significant interaction of group by time for T/C ratio (p
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285 < 0.05), with an effect size of 0.11. Between groups analysis (table 2) showed
286 statistically significant difference between the sham and SM groups at only one post-
287 intervention time point, night (PM samples, mean difference (MD), -0.91; 95% CI: -
289
291 There was a statistically significant interaction of group by time for salivary
292 cortisol concentration (p < .001), with an effect size of 0.28. Pairwise comparison
293 between groups (table 2) at each post-intervention time points revealed a statistically
294 significant difference between the sham group and SM group at 5 minutes post-
295 intervention (mean difference (MD), 0.35; 95% CI: 0.12 to 0.6). However, no
296 statistically significant interaction of group by time was found for salivary cortisol at
13
298 that salivary cortisol levels were lower (significant) post-intervention (5 and 30
301 No statistically significant interaction of group by time was found for salivary
302 testosterone levels (p=0.33), with an effect size of 0.05. No statistically significant
303 difference was found between or within groups at any of the post-intervention time
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307 No statistically significant interaction of group by time was found for HRV
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308 (p=0.75), with an effect size of 0.13. No statistically significant difference (between or
309 within groups) was found for HRV at any of the post-intervention time points (table
310 3).
311 Oxy-haemoglobin
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312 No statistically significant interaction of group by time was found for OHB
313 (p=0.32), with an effect size of 0.05. No statistically significant difference (between
314 groups) was found in OHB concentration at any post-intervention time points (table
319
14
320 DISCUSSION
321
323 change in HP axis activity, as observed by the T/C ratio, salivary cortisol and OHB
325 ratio approximately 6 hours post-intervention and salivary cortisol levels at 5-minutes
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326 post-intervention. Though statistical significance between groups was not achieved
327 for OHB or HRV, decreases in OHB levels suggest an immediate vasoconstriction
330 Our study found that the T/C ratio was significantly lower in the SM group
331 compared to the sham group 6 hours post-intervention. This may be because of
332 changes in cortisol levels as the testosterone levels were similar in both groups 6
333 hours following intervention. When compared with the sham group (Mean Difference
334 (MD)- 0.58), a lesser drop in salivary cortisol levels was evidenced from 30-minutes
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335 post-intervention to 6 hours post-intervention in the SM group (MD- 0.14). This may
337 Cortisol has widespread effects on glucose, fat and protein metabolism and
338 can stimulate gluconeogenesis that can be used as building blocks of tissue repair25;
339 thereby playing an important role in tissue healing. It is important to note that tissue
340 healing is a complex process and may be influenced by other hormones produced by
341 the pituitary such as growth hormone and thyroid hormone63. However, to measure
342 these were beyond the scope of this study. On the other hand, elevated cortisol level
343 has been associated with dysregulated insulin, impaired glucose metabolism,
15
344 abdominal obesity, osteoporosis, hyperlipidemia and hypertension 7,53,91. Therefore,
345 our findings should be interpreted with caution and need to be verified by future
347 The T/C ratio had been widely used in sports and exercise science research
348 as an indicator of overtraining and recovery. To our knowledge, this is the first study
349 to investigate the effects of thoracic SM on T/C ratio. Previously, studies have used
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350 only cortisol as an indicator of HPA axis activity13,64,66,90. However, it is now clear
351 that the HPA axis can be influenced by other endocrine mechanisms (HPG axis
352 specifically). Hence, it has been advocated that the balance between these two
353 hormones may provide a better estimation of HPA axis activity3,19. The exact clinical
354 utility of changes in T/C ratio noted in our study is unclear. Despite this, our findings
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355 may provide a platform for future studies to explore further on this area of manual
358 There was a significant decrease in salivary cortisol levels at 5-minutes post-
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359 intervention in the SM group compared to sham group. Cortisol is regulated by the
360 HPA axis through feedforward and feedback loops11,92. The glucocorticoid mediated
361 feedback loop operates in at least three time domains: fast (within seconds to
362 minutes), intermediate (2 to 10 hours) and slow (over hours to days)44. Animal
363 models further demonstrate that an innocuous stimulus (such as SM) applied to the
364 spine can have inhibitory effects on adrenal gland activity10. Therefore it could be
365 argued that immediate (5 minutes) drop in cortisol level was through reflexive
366 inhibition in adrenal activity via SM. This is in contrast with findings from previous
367 studies13,90 that reported no changes in cortisol levels immediately following a SM.
16
368 While our intervention was a thoracic SM; Whelan et al (2002) used an upper
369 cervical SM; it is unclear whether Christian et al (1998) used a cervical or a thoracic
370 SM or both. Our data collection happened in the afternoon when cortisol levels are
371 shown to be more stable; whereas, the salivary/plasma cortisol were collected during
372 late morning in the other studies13,90, which may partly explain the difference in
373 findings.
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374 The drop in cortisol at 5 minutes post-intervention may then trigger feedback
376 following SM. However, it is to be noted that many factors including the circadian
377 rhythm, ultradian rhythms and stress levels (to name a few) may influence blood
378 corticosterone concentrations58. The PSS-10 scores were similar in both groups.
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379 Hence, the difference in cortisol levels may not be due to difference in baseline
380 perceived stress levels. Most participants in our study received SM for the first time.
381 It could be argued that the participants perceived the act of SM as stressful. If this
382 was true, then an increase in cortisol levels should have been noticed immediately
383 rather than many hours following SM. However, we found no significant changes in
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384 salivary cortisol levels between the two groups at 30-minutes post-intervention. This
385 is in agreement with previous findings66. Therefore our finding strengthens the fact
386 that the act of SM itself may not induce a state of stress as noted previously85.
387 Alternatively it could be argued that SM had an influence on the opioid system;
388 thereby, influencing the HPA axis6. However, this can only be speculated as we did
390 The baseline salivary cortisol and testosterone levels reported in our study are
391 consistent with the literature38. Both cortisol and testosterone exhibit circadian
392 rhythmicity with peak concentrations in the morning and reduced concentrations in
17
393 the evening and overnight84. As mentioned previously, the circadian rhythmicity of
395 these confounding factors were addressed in previous studies13,64,90 which may also
396 partly explain the conflicting results reported in the studies. Therefore, participants in
397 our study had to follow a strict protocol before saliva collection (refer supplement).
398 Also, the data collection happened only on Wednesday and Thursday as the day of
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399 data collection (weekend vs. week days) has been shown to influence stress and
400 hence cortisol levels46. Calculating the inter-day reliability (i.e., ICC) for both the
401 hormones therefore was a crucial aspect of our design. The ICC calculated for
402 morning and afternoon cortisol and testosterone concentration in this study are
403 consistent with the literature39,90. Establishing the ICC enabled reliable analysis of
405 Oxy-haemoglobin
406 Findings from our study indicated that within SM group, OHB reduced
407 immediately (one minute) after thoracic SM and steadily rose with changes at 30-
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408 minutes being statistically different from baseline, 1-minute and 5-minute values. It is
409 to be noted that between group changes did not reach statistical significance.
410 Previously studies investigating the effects of SM have routinely used skin blood flow
411 (SBF) as a measure of SNS activity. However, as SBF is not only mediated by the
412 SNS, but is also dependant on many other factors20, interpretation of changes have
414 (2014), not only were the included studies heterogeneous in nature, but the extent to
415 which SBF changes reflect SNS changes in deeper tissues still remains unclear 93.
416 Therefore, we used NIRS to measure OHB changes in calf muscle as an indicator
417 of SNS activity. NIRS has been shown to reliably measure changes in skeletal
18
418 muscle blood flow when compared to established methods such as Doppler
420 Our study did not find significant between group changes in OHB of calf
421 muscle. Research has shown that SM elicits extra segmental effects and changes in
422 SNS activity has been suggested as one possible explanation for these effects. By
423 measuring blood flow in calf muscle, which has no segmental connection to the
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424 thoracic spine, extra segmental effects of thoracic SM via the SNS could be
425 assessed. Absence of significant between group changes in OHB found in our study
426 may reflect ongoing challenges with regards to measuring autonomic activity 93.
427 Further, the precise location and extent of vasoconstriction within skeletal muscle
428 following SNS activation can be difficult to ascertain83. Alternatively, other reliable
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432 No significant difference in HRV (LF/HF ratio) between the sham and the SM groups
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433 was found. A thoracic SM could have a stimulatory action on the ANS (especially the
434 SNS); considering the anatomical and physiological relationship of the thoracic spine
435 and the SNS. Similar to previous findings76,87 we found no changes in HRV values
436 following a thoracic SM. However this is in contrast to Budgell and Polus 9 who
437 reported that a prone HVLA of thoracic spine may influence the autonomic output to
438 the heart that is not duplicated by a sham procedure. It is important to note that the
439 SM technique used in our study (supine HVLA thrust) is different from that used in
440 the other study (prone HVLA thrust). Therefore, the results may not be comparable.
441 There have been disagreements over the accuracy of LF/HF ratio as a marker of
19
442 cardiac autonomic activity5,57,73. For instance, some authors dispute the direct
444 the modulating baroreflex activity33,61. The inaccuracy of the test may also be a
445 reason why the findings are different between studies. However ratios of spectral
446 power (LF/HF ratio) continue to be used in research to provide better information
448 In summary, our findings indicate a quick response from the SNS followed by
449 a longer lasting slow response from neuroendocrine system following SM. This may
450 provide justification for the use of SM in the early phases of injury to enhance
451 physiological processes either before the patient can start exercising or as an
452 adjunct to exercise, regardless of the site of injury. Previous manual therapy studies
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453 have explored individual biomechanical30 and neurophysiological effects86 with the
454 potential interaction of these effects often being overlooked4. In chronic pain
455 population however, dysregulation of both the ANS and the HPA axis have been
456 reported74. Therefore, our findings may provide preliminary evidence for the
457 combined effects (i.e. neuroendocrine) of thoracic SM, the therapeutic benefits of
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459
461 One of the major strength of the study is its design. We used a repeated
462 measures design collecting salivary samples at different time points as indicated by
463 a review2. We were able to successfully address various methodological factors that
464 could confound hormonal measurements. The atmospheric chamber used during the
465 experiment allowed us to control various parameters such as the temperature and
20
466 humidity, which are known to have an effect on endocrine as well as ANS functions.
467 Further, measuring testosterone to enable calculation of the T/C ratio, an indicator of
468 HPA activity is also unique to our study. This may improve our understanding of
469 complex interactive hormonal response to SM. The use of NIRS to measure SNS
470 activity is also novel to our study. Because of the one-off nature of the intervention
471 used in this study, there was no missing data or attrition of participants.
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472 The study is not without its limitations. The effect size for T/C ratio (0.11) and
473 cortisol (0.28) changes noted in our study can be considered as medium16,22. This
475 individuals and has been shown to be amplified in painful population 59,62. Therefore,
476 the magnitude of effects should be bigger in symptomatic population and needs to
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477 be verified by future research. Females were not included in the current study
478 because it is well known that the HPA and HPG axis response differs between men
479 and women, especially during menstrual cycle and contraceptive usage 19,47. Future
480 research would either stratify participants by gender or adjust the hormonal data
481 (females) for known confounders. We found changes in HP axis activity following SM
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483 An apriori power calculation to determine the sample size was undertaken to
484 achieve an effect size of 0.25. This effect size can be considered as medium effect
485 size22. Further, a study71 indicated that a minimum of 24 participants are required for
486 studies involving HRV. Hence a sample size of 24 was considered adequate for this
487 mechanistic study. However, it is to be noted that the power calculations were not
488 based on the minimally clinically important difference (MCID) of the primary outcome
489 measures which are currently unknown. Therefore the possibility of a type-II error
490 cannot be ruled out. We expect minimal chance bias as baseline difference between
21
491 groups were not substantial and we consider our randomisation process as
492 successful.
493 CONCLUSION
494
496 salivary cortisol immediately and T/C ratio many hours following SM. A thoracic SM
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497 may also have immediate effects on the SNS as indicated by OHB levels. The
498 clinical implication of these changes are however unclear. More research is therefore
501 Findings: Thoracic spinal manipulation can reduce salivary cortisol levels
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503 Implications: This study may provide preliminary evidence that thoracic spinal
504 manipulation may influence tissue healing via modulation of the neuroendocrine
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505 system.
506 Cautions: this studys findings are based on healthy male participants. Therefore, the
510
22
511 REFERENCES
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773
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774 Figure Legends
775 1) FIGURE 1. Illustration of SM technique (large photo) with hand position (top
777
778
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784
785
786
29
Journal of Orthopaedic & Sports Physical Therapy
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793
792
791
790
789
788
787
3) FIGURE 3. Flow of participants
30
4) FIGURE 4. Changes in T/C ratio between groups following intervention
TABLE 1. Baseline characteristics of participants
Testosterone/Cortisol.
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* p<0.05
Journal of Orthopaedic & Sports Physical Therapy
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Outcome Groups (mean and SD) Interaction Difference between groups: SM - sham
(MD and CI; p-value*)
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B P1 P2 P3 P1 P2 P3
SM Sham SM Sham SM Sham SM Sham p-value Effect
(n = 12) (n = 12) (n = 12) (n = 12) (n = 12) (n = 12) (n = 12) (n = 12) Size
Cortisol -0.78(.24) -0.99(.25) -0.99(.27) -0.64(.29) -0.93(.29) -0.73 (.32) -1.07(.26) -1.31(.42) <0.01 0.28 -0.35(-.59 to -12 -0.20(-.46to 0.23(-.06to0.53;0.11)
;0.005) .05;0.11)
115(45.4) 149(68.6) 151(58.7) 141(67.6) 157(67.4) 164 (59.3) 81(25.6) 94(51.8) 0.33 0.05 10.08(-43.5to63.8; -6.29(-60 -12.87(-47.5to
Journal of Orthopaedic & Sports Physical Therapy
Testosterone
0.70) to47.5;0.8 21.8;0.45)
1)
T/C ratio .29(.036) .36(.036) .34(.032) .30(.032) .35(.033) .35(.033) .30(.026) .39(.026) <0.05 0.11 0.04(-0.05to0.13; 0.00(- 0.09(-0.16to-
0.38) 0.09to0.0 0.09;0.02)
9; 1.0)
Abbreviations: CI, Confidence Interval; MD, Mean Difference; B, Pre-intervention samples; P1, Post-intervention samples (5 minutes); P2,
Post-intervention samples (30 minutes); P3, Post-intervention samples (6 hours); SD, Standard Deviation; SM, Spinal Manipulation; ,
Outcome Groups (mean and SD) Interaction Difference between groups: SM - sham (MD and CI; p-
Copyright ${year} Journal of Orthopaedic & Sports Physical Therapy. All rights reserved.
value*)
A1 P1 P2 A1 P1 P2
B P1 P2 P1 P2
Abbreviations: CI, Confidence Interval; HRV, Heart rate variability; OHB, Oxy-Haemoglobin; SD, Standard Deviation; SM, Spinal
Manipulation; B, Pre-intervention samples; A1, Post-intervention (O2Hb) samples (1 minute); P1, Post-intervention samples (5 minutes); P2,