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Innocuous mechanical stimulation of the neck and alterations in heart-rate variability in healthy young adults
Autonomic Neuroscience: Basic and Clinical 91 Ž2001. 96–99 www.elsevier.comrlocaterautneu
Innocuous mechanical stimulation of the neck and alterations in heart-rate variability in healthy young adults Brian Budgell a,) , Fumie Hirano b,1 a
College of Medical Technology, Kyoto UniÕersity, Kawahara-cho 53, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan b RMIT UniÕersity-Japan, Shinbashi 6-20-11, Minato-ku, Tokyo, 105-0004, Japan Received 2 April 2001; received in revised form 26 May 2001; accepted 29 May 2001
Abstract The present study examined the effects of cervical spinal manipulation, a widely applied form of physical therapy, which involves innocuous mechanical stimulation, on heart rate and heart-rate variability, in a cohort of healthy young adults. Using a cross-over treatment design, with a one-week washout period and, in contrast to a sham procedure, the authentic manipulation produced significant alterations in both heart rate and measures of heart-rate variability calculated from power spectrum analysis. In particular, there was an increase in the ratio of low-frequency ŽLF.-to-high-frequency ŽHF. components of the power spectrum of heart-rate variability, which may reflect a shift in balance between sympathetic and parasympathetic output to the heart. q 2001 Elsevier Science B.V. All rights reserved. Keywords: Autonomic nervous system; Heart rate; Heart-rate variability; Spinal manipulation
1. Introduction It is well established that noxious physical ŽMoltner et al., 1990; Hsieh et al., 1995. and psychological ŽEkman et al., 1983; Collet et al., 1997. stimulation may effect autonomic and cardiovascular function in humans. It has also previously been reported that innocuous mechanical stimulation of the neck, via spinal manipulation, is capable of eliciting short-term changes in heart rate and blood pressure ŽTran and Kirby, 1977; McKnight and DeBoer, 1988; Nansel et al., 1991; Fujimoto et al., 1999.. However, the results of the various studies have been inconsistent and study designs have been problematic. Hence, the potential of innocuous stimulation to modify sympathetic, parasympathetic and enteric activity remains largely unexplored. In the absence of adequate studies of the effects of innocuous stimulation on autonomic function, the risks, benefits and confounding effects of various forms of physical therapy remain unrevealed. The present study was intended to determine the effects of cervical spinal manipulation, an innocuous form of mechanical stimulation, on heart rate ŽHR. and certain measures of heart-rate variability ŽHRV., specifically the low-frequency ŽLF. and high-frequency )
Corresponding author. Tel.rfax: q81-75-751-3925. E-mail address: [email protected] ŽB. Budgell.. 1 Tel.: q81-3-3437-6907.
ŽHF. components of the power spectrum, which are widely regarded as indicators of autonomic output to the heart.
2. Methods and materials A cohort of 25 healthy young adults Ž20 men, 5 women., aged 21 to 40 years Žmean 28.5 " 6 years., was recruited into a controlled cross-over trial of the effects of authentic cervical spinal manipulation and sham spinal manipulation on heart-rate variability. The experimental protocol was approved by the Human Research Ethics Committee of RMIT University, Melbourne, Australia. Volunteers received a plain language statement explaining all procedures and risks, and provided written informed consent to undergo spinal manipulation. All subjects were normotensive, with sitting blood pressures of 114 " 13 mm Hgr72 " 3 mm Hg on the first day of the experiment. Volunteers were questioned to exclude subjects with: 1. a history of cervical spine surgery, fracture or dislocation; 2. known anatomical abnormality of the cervical spine; 3. a history of cervical trauma within the past three months or persistent symptoms from earlier trauma; 4. a history of cancer; 5. a history of stroke;
1566-0702r01r$ - see front matter q 2001 Elsevier Science B.V. All rights reserved. PII: S 1 5 6 6 - 0 7 0 2 Ž 0 1 . 0 0 3 0 6 - X
B. Budgell, F. Hiranor Autonomic Neuroscience: Basic and Clinical 91 (2001) 96–99
6. a history of positional vertigo; 7. current anticoagulant or steroid therapy; 8. a history of chronic or recurrent inflammatory disease; 9. current litigation for spinal injury. Subjects were recruited on the basis that they did not have current neck and shoulder pain. Prior to each intervention, the subjects were asked to assess the level of neck discomfort, using a visual analogue scale, at the full extent of active left and right cervical rotation. On the visual analogue scale, 0 represented complete comfort and 10 represented Athe worst pain imaginableB. On this basis, the average levels of pain on full active left and right rotation prior to authentic and sham cervical manipulation were 0.35 q 1.13, 0.25 q 0.86, 0.15 q 0.55 and 0.20 q 0.65, respectively. In other words, on the day of the trials, subjects had, at most, trivial levels of neck discomfort at the extremes of active cervical rotation. Additionally, subjects were examined for the presence of carotid bruits or positional vertigo as contraindications to cervical manipulation and so involvement in this study. Data from one subject, who did undergo spinal manipulation, were excluded from analysis due to the presence of an arrhythmia, which might have confounded HRV analysis. Hence, data are presented from 24 subjects. The mechanical stimuli were applied to the first and second ŽC1 and C2. cervical levels. Both sham and authentic manipulations were performed by a licensed doctor of chiropractic who did not participate in data analysis. The order of presentation of the authentic and sham manipulations was determined by a coin toss immediately prior to the first trial for each subject. The manipulations were performed with the subjects in the supine position. The subject’s head was cradled in one of the clinician’s hands and supported at the limit of rotation without extension. For authentic manipulations, the index finger or thumb of the other hand was applied to the posterior arch Žin the case of C1. or over the articular pillar, and a high-velocity, low-amplitude thrust was applied resulting in an audible sound. This is a form of spinal manipulation conventionally applied in the clinical setting and commonly referred to as a Asupine cervical rotary adjustmentB. The sham manipulation involved supporting the subject’s head at the limit of rotation without extension, making contact with the skin of the neck as if to perform an authentic manipulation, but applying the thrust along the plane of the skin. No sham manipulation was accompanied by an audible sound. The entire process of raising the subject’s head, moving it into rotation, applying the manipulation and returning the head gently to the examination table would not normally take more than 5 s. The electrocardiogram ŽECG. recording during that period of manipulation was excluded from the analysis. Throughout the course of each experiment, ECG was monitored using disposable electrodes Žblue sensor, Medi-
97
cotest, Denmark. with the negative electrode immediately beneath the suprasternal notch, positive electrode at the left anterior-axillary line in the fifth intercostal space, and an indifferent electrode on the right mid-axillary line ŽCM-5 lead.. The ECG signal was fed through a PowerLabr4ST bioamplifier ŽADInstruments, Castle Hill, Australia. and stored on a personal computer ŽMacintosh Powerbook 5300cs, Apple Japan. for analysis off-line. ECG records were analysed using the software Chart v3.6.3 with HRV extension v1.0.1 ŽADInstruments.. Fiveminute blocks of pre- and posttreatment ECG were analysed for heart rate and power spectrum, i.e. absolute and normalized low-frequency component ŽLF., absolute and normalized high-frequency component ŽHF., and the ratio of LFrHF. Pre- and posttreatment values were compared via the paired t-test, where data were distributed normally Žnormalized LF and HF, LFrHR and HR., and via the Wilcoxon-signed rank test, where data were not normally distributed Žabsolute LF and HF..
3. Results With respect to the effectiveness of the randomization of presentation of authentic vs. sham spinal manipulations, there were no significant differences in the prestimulation levels of heart rate, LFrHF, or normalized or absolute LF and HF. Measures of heart rate and heart-rate variability before and after the sham and authentic manipulations are presented in Table 1. Table 1 Pre- and postmanipulation measures of heart rate and heart rate variability Premanipulation
Postmanipulation
P
Sham manipulation HR Žbpm. 65.6"2.5 Absolute LF 359.0"76.4 Normalized LF 41.8"4.8 Absolute HF 602.1"152.6 Normalized HF 55.4"4.8 LFrHF 1.38"0.39
63.4"2.3 343.3"75.3 41.3"4.5 589.0"138.3 55.9"4.5 1.41"0.55
- 0.0001 Žt. 0.916 Žw. 0.850 Žt. 0.843 Žw. 0.867 Žt. 0.948 Žt.
Authentic manipulation HR Žbpm. 67.3"2.4 Absolute LF 240.0"97.3 Normalized LF 38.3"4.7 Absolute HF 314.7"63 Normalized HF 54.1"4.8 LFrHF 1.03".21
63.9"2.1 307.9"83.5 45.0"5.1 411.2"90 52.2"5.1 1.46"0.30
- 0.0001 Žt. 0.0310 Žw. 0.0061 Žt. 1.000 Žw. 0.6710 Žt. 0.0037 Žt.
Measures of heart rate ŽHR. in beats per minute, absolute and normalized low-frequency components ŽLF., absolute and normalized high-frequency components ŽHF. and ratio of low-frequency-to-high-frequency components ŽLFrHF. of the power spectrum of heart rate variability Žmean" S.E.M.. before and after sham and authentic manipulative procedures. P values indicate probability of the null hypothesis that there is no difference between pre- and postmanipulative values per paired t-test Žt. for normally distributed data or Wilcoxon-signed rank test Žw. for data which were not normally distributed.
98
B. Budgell, F. Hiranor Autonomic Neuroscience: Basic and Clinical 91 (2001) 96–99
Not surprisingly, heart rate declined from the first to the second 5 min of the experiment, i.e. pre- to poststimulation, regardless of whether the subjects received authentic or sham spinal manipulation. However, the decline with authentic manipulation Žy3.36 bpm. was greater than the decline with sham manipulation Žy2.13 bpm., the difference being just barely significant Ž p s 0.0496. per a onetailed paired t-test. On the other hand, in subjects undergoing authentic spinal manipulation, there were significant increases in absolute ŽLF. and normalized ŽLFrtotal power. levels of the low-frequency component of the power spectrum, and in the ratio ŽLFrHF. of low-frequency to high-frequency components. In subjects undergoing sham spinal manipulation, there were no changes in the low-frequency or highfrequency components of the power spectrum, nor in the ratio of the two. Pre- and postmanipulation data were plotted prior to analysis, and where the distribution was not convincingly normal Žabsolute low-frequency and absolute high-frequency components., the data were compared using the Wilcoxon-signed rank test. Where data were normally distributed, data were analyzed using a two-tailed paired t-test, with p - 0.05 considered significant. Subjects were asked to rate the level of discomfort of the cervical stimulation on a visual analogue pain scale on which 0 represented complete comfort and 10 represented Athe worst pain imaginableB. All subjects rated the sham manipulation as completely comfortable. Twenty-three of twenty-four subjects rated the authentic manipulation as completely comfortable. One subject gave the authentic manipulation a rating of 2 out of 10 on the pain scale. Hence, both the sham and authentic manipulations could be considered essentially innocuous. Prior to the experiment, all subjects had received a written explanation allowing them to anticipate a cervical manipulation accompanied by an audible sound. Prior to the experiment, they were not aware that they might receive a sham manipulation. On questioning after each experiment, all subjects correctly identified when they had received an authentic manipulation. Three of twenty-four subjects guessed that they had received an authentic manipulation on the occasion that they had received a sham manipulation. Hence, the subjects were not generally blinded to whether they were receiving the authentic or the sham manipulation.
4. Discussion In the cohort of healthy young adults described herein, authentic spinal manipulation was associated with changes in heart rate and heart-rate variability, which could not be duplicated with sham manipulation. The distinguishing features of the authentic manipulation are the high-velocity, low-amplitude thrust applied to and resulting in cavita-
tion of an intervertebral joint. The authentic manipulative procedure employed in this study has been widely used in clinical trials of the effects of spinal manipulation on headache and biomechanical disorders of the neck ŽBoline et al., 1995; Nilsson, 1995; Nilsson et al., 1997; Rogers, 1997; Bove and Nilsson, 1998; Van Schalkwyk and Parkin-Smith, 2000., as well as in a basic physiological study ŽFujimoto et al., 1999. and case report ŽIgarashii and Budgell, 2000.. Both authentic and sham manipulations involved rotation of the neck to approximately the physiological limit. Both applied a rapid, innocuous mechanical stimulation to the skin. Both also probably involved a very low-amplitude movement of the head into extension and rotation with the thrust, although this movement might have been greater with the authentic manipulation. In seeking to explain the observed effects, one is necessarily drawn to mechanisms involving afferent input from receptors in cervical tissues. However, it is also necessary to consider alternative explanations. Importantly, one cannot overlook the lack of blinding of subjects to the authentic vs. factitious manipulation. The audible and often palpable click, which characterizes the authentic procedure, is unavoidable. Without knowing the importance that this feature has for the subject, it is not possible to rule out a role for psychological factors in the physiological effects described. This possibility, however, must be examined in light of the reportedly innocuous nature of both types of manipulation. A second mechanism worthy of consideration is vestibular stimulation. The intent of the authentic cervical manipulation is to impart motion to a vertebra, while the head is stabilized. Visual observation confirms only lowamplitude head movement during cervical manipulation. However, no scrupulous studies have been undertaken to calculate acceleration or its higher order derivatives, which could provide substantial vestibular stimulation despite the small amplitude of movement. It is clear that both in humans and animals vestibular stimulation may elicit cardiovascular reflexes. Yates et al. Ž1991. have described a polysynaptic, inhibitory vestibulosympathetic reflex mediated by neurons in the subretrofacial nucleus of the ventrolateral medulla of the cat. Many of the neurons in the ventrolateral medulla, which responded to vestibular nerve stimulation, also responded to stimulation of the carotid sinus nerve, suggesting a role in cardiovascular regulation. In animals with a mid-cervical spinal transection, to eliminate the influence of visceral receptors, vertical and horizontal movements of the head were shown to influence rostral ventrolateral medullary cells, which received inputs principally from the otolith organ ŽYates et al., 1993.. Renal sympathetic nerve activity has also been shown to be modulated by stimulation of the utricular and saccular nerves in cats ŽZakir et al., 2000.. Additionally, low-amplitude accelerations of the head have been shown to produce short-latency responses in heart rate in humans, with the
B. Budgell, F. Hiranor Autonomic Neuroscience: Basic and Clinical 91 (2001) 96–99
latency of the response prolonged in subjects with vestibular dysfunction ŽRadtke et al., 2000.. With regard to the role of neck afferents, in this instance, it would appear that the stimulation applied was essentially innocuous. Hence, attention is drawn to the role of low-threshold mechanoreceptors in the cervical spine and adjacent musculotendinous tissues. In general, studies in anesthetized animals have demonstrated weak and inconsistent influences of innocuous muscle and joint stimulation on cardiovascular function ŽSato et al., 1997.. The great majority of studies of musculoskeletal influences on autonomic function have involved stimulation of appendicular tissues. In fact, there is evidence from decerebrate cats that input from cervical mechanoreceptors interacts in an antagonistic way with input from the vestibular system to modify the activity of the sympathetic nervous system ŽBolton et al., 1998.. However, there is, as of yet, little convincing evidence that in humans low-threshold mechanoreceptors in the neck are capable of influencing sympathetic activity ŽBolton and Ray, 2000..
5. Conclusions An authentic spinal manipulative procedure, executed in the supine position, was associated with changes in heart rate and autonomic output to the heart in healthy young adults. Similar effects were not elicited by a sham procedure. The distinguishing features of the authentic procedure are a high-velocity, low-amplitude thrust directed to and resulting in audible cavitation of an intervertebral joint. Among mechanisms which might account for the observed effects, the following must be considered: psychological mechanisms resulting from a lack of blinding of the subjects, vestibular stimulation, and stimulation of low-threshold mechanoreceptors in the cervical spine and adjacent musculotendinous tissues.
Acknowledgements This work was supported, in part, by research funds from RMIT University-Japan.
References Boline, P.D., Kassak, K., Bronfort, G., Nelson, C., Anderson, A.V., 1995. Spinal manipulation vs. amitriptyline for the treatment of chronic tension-type headaches: a randomized clinical trial. J. Manipulative Physiol. Ther. 18, 148–154. Bolton, P.S., Ray, C., 2000. Neck afferent involvement in cardiovascular control during movement. Brain Res. Bull. 53, 45–49.
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Bolton, P.S., Kerman, I.A., Woodring, S.F., Yates, B.J., 1998. Influences of neck afferents on sympathetic and respiratory nerve activity. Brain Res. Bull. 47, 413–419. Bove, G., Nilsson, N., 1998. Spinal manipulation in the treatment of episodic tension-type headache. JAMA, J. Am. Med. Assoc. 280, 1576–1579. Collet, C., Vernet-Maury, E., Delhomme, G., Dittmar, A., 1997. Autonomic nervous system response patterns specificity to basic emotions. J. Auton. Nerv. Syst. 62, 45–57. Ekman, P., Levenson, R.W., Friesen, W.V., 1983. Autonomic nervous system activity distinguishes among emotions. Science 221, 1208– 1210. Fujimoto, T., Budgell, B., Uchida, S., Suzuki, A., Meguro, K., 1999. Arterial tonometry in the measurement of the effects of innocuous mechanical stimulation of the neck on heart rate and blood pressure. J. Auton. Nerv. Syst. 75, 109–115. Hsieh, J., Stahle-Backdahl, M., Hagermark, O., Stone-Elander, S., Rosenquist, G., Ingvar, M., 1995. Traumatic nociceptive pain activates the hypothalamus and the periaqueductal gray: a positron emission tomography study. Pain 64, 303–314. Igarashii, Y., Budgell, B., 2000. Case study: response of arrhythmia to spinal manipulation: monitoring by ECG with analysis of heart-rate variability. Chiropractic J. Aust. 30, 92–95. McKnight, M.E., DeBoer, K.F., 1988. Preliminary study of blood pressure changes in normotensive subjects undergoing chiropractic care. J. Manipulative Physiol. Ther. 11, 261–266. Moltner, A., Holzl, R., Strian, F., 1990. Heart rate changes as an autonomic component of the pain response. Pain 43, 81–89. Nansel, D., Jansen, R., Cremata, E., Dhami, M.S.I., Holley, D., 1991. Effects of cervical adjustments on lateral-flexion passive end-range asymmetry and on blood pressure, heart rate and plasma catecholamine levels. J. Manipulative Physiol. Ther. 8, 450–456. Nilsson, N., 1995. A randomized controlled trial of the effect of spinal manipulation in the treatment of cervicogenic headache. J. Manipulative Physiol. Ther. 18, 435–440. Nilsson, N., Christensen, H.W., Hartvigsen, J., 1997. The effect of spinal manipulation in the treatment of cervicogenic headache. J. Manipulative Physiol. Ther. 20, 326–330. Radtke, A., Popov, K., Bronstein, A.M., Gresty, M.A., 2000. Evidence for a vestibulo-cardiac reflex in man. Lancet 356, 736–737. Rogers, R.G., 1997. The effects of spinal manipulation on cervical kinesthesia in patients with chronic neck pain: a pilot study. J. Manipulative Physiol. Ther. 20, 80–85. Sato, A., Sato, Y., Schmidt, R.F., 1997. The impact of somatosensory input on autonomic functions. Rev. Physiol., Biochem. Pharmacol. 130, 115–166. Tran, T.A., Kirby, J.D., 1977. The effects of upper cervical adjustment upon the normal physiology of the heart. ACA J. Chiropractic 11, S58–S62. Van Schalkwyk, R., Parkin-Smith, G.F., 2000. A clinical trial investigating the possible effect of the supine cervical rotatory manipulation and the supine lateral break manipulation in the treatment of mechanical neck pain: a pilot study. J. Manipulative Physiol. Ther. 23, 324–331. Yates, B.J., Yamagata, Y., Bolton, P.S., 1991. The ventrolateral medulla of the cat mediates vestibulosympathetic reflexes. Brain Res. 552, 265–272. Yates, B.J., Goto, T., Bolton, P.S., 1993. Responses of neurons in the rostral ventrolateral medulla of the cat to natural vestibular stimulation. Brain Res. 601, 255–264. Zakir, M., Ono, S., Meng, H., Uchino, Y., 2000. Saccular and utricular influences on sympathetic nerve activities in cats. Exp. Brain Res. 134, 402–406.
Innocuous mechanical stimulation of the neck and alterations in heart-rate variability in healthy young adults Brian Budgell a,) , Fumie Hirano b,1 a
College of Medical Technology, Kyoto UniÕersity, Kawahara-cho 53, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan b RMIT UniÕersity-Japan, Shinbashi 6-20-11, Minato-ku, Tokyo, 105-0004, Japan Received 2 April 2001; received in revised form 26 May 2001; accepted 29 May 2001
Abstract The present study examined the effects of cervical spinal manipulation, a widely applied form of physical therapy, which involves innocuous mechanical stimulation, on heart rate and heart-rate variability, in a cohort of healthy young adults. Using a cross-over treatment design, with a one-week washout period and, in contrast to a sham procedure, the authentic manipulation produced significant alterations in both heart rate and measures of heart-rate variability calculated from power spectrum analysis. In particular, there was an increase in the ratio of low-frequency ŽLF.-to-high-frequency ŽHF. components of the power spectrum of heart-rate variability, which may reflect a shift in balance between sympathetic and parasympathetic output to the heart. q 2001 Elsevier Science B.V. All rights reserved. Keywords: Autonomic nervous system; Heart rate; Heart-rate variability; Spinal manipulation
1. Introduction It is well established that noxious physical ŽMoltner et al., 1990; Hsieh et al., 1995. and psychological ŽEkman et al., 1983; Collet et al., 1997. stimulation may effect autonomic and cardiovascular function in humans. It has also previously been reported that innocuous mechanical stimulation of the neck, via spinal manipulation, is capable of eliciting short-term changes in heart rate and blood pressure ŽTran and Kirby, 1977; McKnight and DeBoer, 1988; Nansel et al., 1991; Fujimoto et al., 1999.. However, the results of the various studies have been inconsistent and study designs have been problematic. Hence, the potential of innocuous stimulation to modify sympathetic, parasympathetic and enteric activity remains largely unexplored. In the absence of adequate studies of the effects of innocuous stimulation on autonomic function, the risks, benefits and confounding effects of various forms of physical therapy remain unrevealed. The present study was intended to determine the effects of cervical spinal manipulation, an innocuous form of mechanical stimulation, on heart rate ŽHR. and certain measures of heart-rate variability ŽHRV., specifically the low-frequency ŽLF. and high-frequency )
Corresponding author. Tel.rfax: q81-75-751-3925. E-mail address: [email protected] ŽB. Budgell.. 1 Tel.: q81-3-3437-6907.
ŽHF. components of the power spectrum, which are widely regarded as indicators of autonomic output to the heart.
2. Methods and materials A cohort of 25 healthy young adults Ž20 men, 5 women., aged 21 to 40 years Žmean 28.5 " 6 years., was recruited into a controlled cross-over trial of the effects of authentic cervical spinal manipulation and sham spinal manipulation on heart-rate variability. The experimental protocol was approved by the Human Research Ethics Committee of RMIT University, Melbourne, Australia. Volunteers received a plain language statement explaining all procedures and risks, and provided written informed consent to undergo spinal manipulation. All subjects were normotensive, with sitting blood pressures of 114 " 13 mm Hgr72 " 3 mm Hg on the first day of the experiment. Volunteers were questioned to exclude subjects with: 1. a history of cervical spine surgery, fracture or dislocation; 2. known anatomical abnormality of the cervical spine; 3. a history of cervical trauma within the past three months or persistent symptoms from earlier trauma; 4. a history of cancer; 5. a history of stroke;
1566-0702r01r$ - see front matter q 2001 Elsevier Science B.V. All rights reserved. PII: S 1 5 6 6 - 0 7 0 2 Ž 0 1 . 0 0 3 0 6 - X
B. Budgell, F. Hiranor Autonomic Neuroscience: Basic and Clinical 91 (2001) 96–99
6. a history of positional vertigo; 7. current anticoagulant or steroid therapy; 8. a history of chronic or recurrent inflammatory disease; 9. current litigation for spinal injury. Subjects were recruited on the basis that they did not have current neck and shoulder pain. Prior to each intervention, the subjects were asked to assess the level of neck discomfort, using a visual analogue scale, at the full extent of active left and right cervical rotation. On the visual analogue scale, 0 represented complete comfort and 10 represented Athe worst pain imaginableB. On this basis, the average levels of pain on full active left and right rotation prior to authentic and sham cervical manipulation were 0.35 q 1.13, 0.25 q 0.86, 0.15 q 0.55 and 0.20 q 0.65, respectively. In other words, on the day of the trials, subjects had, at most, trivial levels of neck discomfort at the extremes of active cervical rotation. Additionally, subjects were examined for the presence of carotid bruits or positional vertigo as contraindications to cervical manipulation and so involvement in this study. Data from one subject, who did undergo spinal manipulation, were excluded from analysis due to the presence of an arrhythmia, which might have confounded HRV analysis. Hence, data are presented from 24 subjects. The mechanical stimuli were applied to the first and second ŽC1 and C2. cervical levels. Both sham and authentic manipulations were performed by a licensed doctor of chiropractic who did not participate in data analysis. The order of presentation of the authentic and sham manipulations was determined by a coin toss immediately prior to the first trial for each subject. The manipulations were performed with the subjects in the supine position. The subject’s head was cradled in one of the clinician’s hands and supported at the limit of rotation without extension. For authentic manipulations, the index finger or thumb of the other hand was applied to the posterior arch Žin the case of C1. or over the articular pillar, and a high-velocity, low-amplitude thrust was applied resulting in an audible sound. This is a form of spinal manipulation conventionally applied in the clinical setting and commonly referred to as a Asupine cervical rotary adjustmentB. The sham manipulation involved supporting the subject’s head at the limit of rotation without extension, making contact with the skin of the neck as if to perform an authentic manipulation, but applying the thrust along the plane of the skin. No sham manipulation was accompanied by an audible sound. The entire process of raising the subject’s head, moving it into rotation, applying the manipulation and returning the head gently to the examination table would not normally take more than 5 s. The electrocardiogram ŽECG. recording during that period of manipulation was excluded from the analysis. Throughout the course of each experiment, ECG was monitored using disposable electrodes Žblue sensor, Medi-
97
cotest, Denmark. with the negative electrode immediately beneath the suprasternal notch, positive electrode at the left anterior-axillary line in the fifth intercostal space, and an indifferent electrode on the right mid-axillary line ŽCM-5 lead.. The ECG signal was fed through a PowerLabr4ST bioamplifier ŽADInstruments, Castle Hill, Australia. and stored on a personal computer ŽMacintosh Powerbook 5300cs, Apple Japan. for analysis off-line. ECG records were analysed using the software Chart v3.6.3 with HRV extension v1.0.1 ŽADInstruments.. Fiveminute blocks of pre- and posttreatment ECG were analysed for heart rate and power spectrum, i.e. absolute and normalized low-frequency component ŽLF., absolute and normalized high-frequency component ŽHF., and the ratio of LFrHF. Pre- and posttreatment values were compared via the paired t-test, where data were distributed normally Žnormalized LF and HF, LFrHR and HR., and via the Wilcoxon-signed rank test, where data were not normally distributed Žabsolute LF and HF..
3. Results With respect to the effectiveness of the randomization of presentation of authentic vs. sham spinal manipulations, there were no significant differences in the prestimulation levels of heart rate, LFrHF, or normalized or absolute LF and HF. Measures of heart rate and heart-rate variability before and after the sham and authentic manipulations are presented in Table 1. Table 1 Pre- and postmanipulation measures of heart rate and heart rate variability Premanipulation
Postmanipulation
P
Sham manipulation HR Žbpm. 65.6"2.5 Absolute LF 359.0"76.4 Normalized LF 41.8"4.8 Absolute HF 602.1"152.6 Normalized HF 55.4"4.8 LFrHF 1.38"0.39
63.4"2.3 343.3"75.3 41.3"4.5 589.0"138.3 55.9"4.5 1.41"0.55
- 0.0001 Žt. 0.916 Žw. 0.850 Žt. 0.843 Žw. 0.867 Žt. 0.948 Žt.
Authentic manipulation HR Žbpm. 67.3"2.4 Absolute LF 240.0"97.3 Normalized LF 38.3"4.7 Absolute HF 314.7"63 Normalized HF 54.1"4.8 LFrHF 1.03".21
63.9"2.1 307.9"83.5 45.0"5.1 411.2"90 52.2"5.1 1.46"0.30
- 0.0001 Žt. 0.0310 Žw. 0.0061 Žt. 1.000 Žw. 0.6710 Žt. 0.0037 Žt.
Measures of heart rate ŽHR. in beats per minute, absolute and normalized low-frequency components ŽLF., absolute and normalized high-frequency components ŽHF. and ratio of low-frequency-to-high-frequency components ŽLFrHF. of the power spectrum of heart rate variability Žmean" S.E.M.. before and after sham and authentic manipulative procedures. P values indicate probability of the null hypothesis that there is no difference between pre- and postmanipulative values per paired t-test Žt. for normally distributed data or Wilcoxon-signed rank test Žw. for data which were not normally distributed.
98
B. Budgell, F. Hiranor Autonomic Neuroscience: Basic and Clinical 91 (2001) 96–99
Not surprisingly, heart rate declined from the first to the second 5 min of the experiment, i.e. pre- to poststimulation, regardless of whether the subjects received authentic or sham spinal manipulation. However, the decline with authentic manipulation Žy3.36 bpm. was greater than the decline with sham manipulation Žy2.13 bpm., the difference being just barely significant Ž p s 0.0496. per a onetailed paired t-test. On the other hand, in subjects undergoing authentic spinal manipulation, there were significant increases in absolute ŽLF. and normalized ŽLFrtotal power. levels of the low-frequency component of the power spectrum, and in the ratio ŽLFrHF. of low-frequency to high-frequency components. In subjects undergoing sham spinal manipulation, there were no changes in the low-frequency or highfrequency components of the power spectrum, nor in the ratio of the two. Pre- and postmanipulation data were plotted prior to analysis, and where the distribution was not convincingly normal Žabsolute low-frequency and absolute high-frequency components., the data were compared using the Wilcoxon-signed rank test. Where data were normally distributed, data were analyzed using a two-tailed paired t-test, with p - 0.05 considered significant. Subjects were asked to rate the level of discomfort of the cervical stimulation on a visual analogue pain scale on which 0 represented complete comfort and 10 represented Athe worst pain imaginableB. All subjects rated the sham manipulation as completely comfortable. Twenty-three of twenty-four subjects rated the authentic manipulation as completely comfortable. One subject gave the authentic manipulation a rating of 2 out of 10 on the pain scale. Hence, both the sham and authentic manipulations could be considered essentially innocuous. Prior to the experiment, all subjects had received a written explanation allowing them to anticipate a cervical manipulation accompanied by an audible sound. Prior to the experiment, they were not aware that they might receive a sham manipulation. On questioning after each experiment, all subjects correctly identified when they had received an authentic manipulation. Three of twenty-four subjects guessed that they had received an authentic manipulation on the occasion that they had received a sham manipulation. Hence, the subjects were not generally blinded to whether they were receiving the authentic or the sham manipulation.
4. Discussion In the cohort of healthy young adults described herein, authentic spinal manipulation was associated with changes in heart rate and heart-rate variability, which could not be duplicated with sham manipulation. The distinguishing features of the authentic manipulation are the high-velocity, low-amplitude thrust applied to and resulting in cavita-
tion of an intervertebral joint. The authentic manipulative procedure employed in this study has been widely used in clinical trials of the effects of spinal manipulation on headache and biomechanical disorders of the neck ŽBoline et al., 1995; Nilsson, 1995; Nilsson et al., 1997; Rogers, 1997; Bove and Nilsson, 1998; Van Schalkwyk and Parkin-Smith, 2000., as well as in a basic physiological study ŽFujimoto et al., 1999. and case report ŽIgarashii and Budgell, 2000.. Both authentic and sham manipulations involved rotation of the neck to approximately the physiological limit. Both applied a rapid, innocuous mechanical stimulation to the skin. Both also probably involved a very low-amplitude movement of the head into extension and rotation with the thrust, although this movement might have been greater with the authentic manipulation. In seeking to explain the observed effects, one is necessarily drawn to mechanisms involving afferent input from receptors in cervical tissues. However, it is also necessary to consider alternative explanations. Importantly, one cannot overlook the lack of blinding of subjects to the authentic vs. factitious manipulation. The audible and often palpable click, which characterizes the authentic procedure, is unavoidable. Without knowing the importance that this feature has for the subject, it is not possible to rule out a role for psychological factors in the physiological effects described. This possibility, however, must be examined in light of the reportedly innocuous nature of both types of manipulation. A second mechanism worthy of consideration is vestibular stimulation. The intent of the authentic cervical manipulation is to impart motion to a vertebra, while the head is stabilized. Visual observation confirms only lowamplitude head movement during cervical manipulation. However, no scrupulous studies have been undertaken to calculate acceleration or its higher order derivatives, which could provide substantial vestibular stimulation despite the small amplitude of movement. It is clear that both in humans and animals vestibular stimulation may elicit cardiovascular reflexes. Yates et al. Ž1991. have described a polysynaptic, inhibitory vestibulosympathetic reflex mediated by neurons in the subretrofacial nucleus of the ventrolateral medulla of the cat. Many of the neurons in the ventrolateral medulla, which responded to vestibular nerve stimulation, also responded to stimulation of the carotid sinus nerve, suggesting a role in cardiovascular regulation. In animals with a mid-cervical spinal transection, to eliminate the influence of visceral receptors, vertical and horizontal movements of the head were shown to influence rostral ventrolateral medullary cells, which received inputs principally from the otolith organ ŽYates et al., 1993.. Renal sympathetic nerve activity has also been shown to be modulated by stimulation of the utricular and saccular nerves in cats ŽZakir et al., 2000.. Additionally, low-amplitude accelerations of the head have been shown to produce short-latency responses in heart rate in humans, with the
B. Budgell, F. Hiranor Autonomic Neuroscience: Basic and Clinical 91 (2001) 96–99
latency of the response prolonged in subjects with vestibular dysfunction ŽRadtke et al., 2000.. With regard to the role of neck afferents, in this instance, it would appear that the stimulation applied was essentially innocuous. Hence, attention is drawn to the role of low-threshold mechanoreceptors in the cervical spine and adjacent musculotendinous tissues. In general, studies in anesthetized animals have demonstrated weak and inconsistent influences of innocuous muscle and joint stimulation on cardiovascular function ŽSato et al., 1997.. The great majority of studies of musculoskeletal influences on autonomic function have involved stimulation of appendicular tissues. In fact, there is evidence from decerebrate cats that input from cervical mechanoreceptors interacts in an antagonistic way with input from the vestibular system to modify the activity of the sympathetic nervous system ŽBolton et al., 1998.. However, there is, as of yet, little convincing evidence that in humans low-threshold mechanoreceptors in the neck are capable of influencing sympathetic activity ŽBolton and Ray, 2000..
5. Conclusions An authentic spinal manipulative procedure, executed in the supine position, was associated with changes in heart rate and autonomic output to the heart in healthy young adults. Similar effects were not elicited by a sham procedure. The distinguishing features of the authentic procedure are a high-velocity, low-amplitude thrust directed to and resulting in audible cavitation of an intervertebral joint. Among mechanisms which might account for the observed effects, the following must be considered: psychological mechanisms resulting from a lack of blinding of the subjects, vestibular stimulation, and stimulation of low-threshold mechanoreceptors in the cervical spine and adjacent musculotendinous tissues.
Acknowledgements This work was supported, in part, by research funds from RMIT University-Japan.
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