Chiropractic’s Mechanism in Pain Modulation and the Connection to Systemic Diseases

A Literature Review and Synthesis on the Possible Effects of Chiropractic on Cancers, Systemic Diseases, Mental and Social Disorders and Sexual Behavior

A report on the scientific literature 

By: Mark Studin DC, FASBE(C), DAAPM, DAAMLP

 William J. Owens DC, DAAMLP

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Citation: Studin M., Owens W. (2016) Chiropractic’s Mechanism in Pain Modulation and the Connection to Systemic Disease, Dynamic Chiropractor 34(3) 26-33

Chiropractors for over a century have been called “quacks” and “charlatans” for reporting what they have observed in their patients as a result of their care. The maladies that chiropractors have witnessed the disappearance of include cancers, eczema, infertility, high blood pressure, diabetes, arthritis, emotional disturbances and many more. Historically, this has brought the “ire” of organized medicine and other splinter groups to attack the chiropractic profession with the mantra of “there is no scientific evidence” to support these allegations. One author of this paper, Dr Studin, has spent 35 years experiencing this phenomenon where patients reported the aforementioned maladies and a long list of other diseases which “miraculously” disappeared with treatment.

To be clear, this wasn’t an isolated instance, but rather year after year that and in meetings with other chiropractor’s similar stories were heard.  However, sharing these findings amongst chiropractors was much easier than sharing it with the healthcare community because of the persecution against chiropractors and the outcry of “quackery.” In fact, many of the chiropractic practitioners who witnessed these results felt the best way to approach this was to only discuss this with patients.  They purposefully avoided any other healthcare providers in these conversations because there was no scientific evidence to back up the repeated observations.

To the medical community, these were religious type beliefs and we, as chiropractors, were proselytizing our religion of chiropractic on patients and the community. Based on the lack of published evidence, their allegations against us was not without merit albeit misguided and fueled in part by economics. However, medicine saw beliefs based upon observations on the chiropractic side and medicine required published evidence for verification no matter the claims and testimonials from an ever-increasing segment of the public. Today, the benefits of chiropractic care have remained constant with the same stream of patients getting well. However, the evidence has now started to support these findings and the chiropractic profession has gone beyond proselytizing our beliefs to being able to cite specific research that supports and justifies chiropractic care as part of mainstream healthcare. We can now share our results, which are consistent with the scientific literature that often has been discovered or proven beyond the chiropractic profession.

NOTE: Although the following evidence verifies what our profession has been witnessing over the last decade, please understand that the research is just beginning to show evidence and much more is needed to bring our profession to where it needs to be. As a result, every practitioner and every chiropractic academic institution needs to both support and be involved in research. Our professional institutions and their research departments MUST take an active and serious role in producing and publishing research. Otherwise, it will come from another source such as osteopathy or physical therapy and prevent chiropractic from taking it’s unique place in healthcare.

Chiropractic Adjustment and Central Nervous System Changes

We have held for quite some time that studying how the adjustment works for the treatment of pain is the first step in truly understanding how the chiropractic adjustment affects systemic diseases. It has been shown that the chiropractic adjustment has a direct effect on many regions in the brain where pain mediation arises. As evidence, Reed, Pickar, Sozio, and Long (2014) reported:

…forms of manual therapy have been clinically shown to increase mechanical pressure pain thresholds (i.e., decrease pain sensitivity) in both symptomatic and asymptomatic subjects.Cervical spinal manipulation has been shown to result in unilateral as well as bilateral mechanical hypoalgesia [reduction in pain]. Compared with no manual therapy, oscillatory spinal manual therapy at T12 and L4 produced significantly higher paraspinal pain thresholds at T6, L1, and L3 in individuals with rheumatoid arthritis. The immediate and widespread hypoalgesia associated with manual therapy treatments has been attributed to alterations in peripheral and/or central pain processing including activation of descending pain inhibitory systems.

Increasing evidence from animal models suggests that manual therapy activates the central nervous system and, in so doing, affects areas well beyond those being treated. (p. 277)

Reed et al. (2014) continued stating, “Several clinical studies indicate that spinal manipulation [chiropractic spinal adjustment] alters central processing of mechanical stimuli evidenced by increased pressure pain thresholds and decreased pain sensitivity in asymptomatic and symptomatic subjects following manipulation” (p. 282).

In another paper, Gay, Robinson, George, Perlstein, and Bishop (2014) reported, “With the evidence supporting efficacy of MT [manual therapy or chiropractic spinal adjustments] to reduce pain intensity and pain sensitivity, it is reasonable to assume that the underlying therapeutic effect of MT is likely to include a higher cortical component” (p. 615).   The authors continued by stating, “…pain-free volunteers processed thermal stimuli applied to the hand before and after thoracic spinal manipulation (a form of MT).  What they found was that after thoracic manipulation, several brain regions demonstrated a reduction in peak BOLD [blood-oxygen-level–dependent] activity. Those regions included the cingulate, insular, motor, amygdala and somatosensory cortices, and the PAG [periaqueductal gray regions]” (Gay et al., 2014, p. 615).

The above two studies are only a small part of a growing body of evidence showing that the chiropractic spinal adjustment directly affects the functioning of the central nervous system and is the core of pain modulation with chiropractic care and the foundation to the next level, as outlined below. 

The Effect of the Chiropractic Adjustment on Neuropeptides (Neurotensin-Oxytocin-Cortisol)

NOOC Axis = Neurotensin-Orexin-Oxytocin-Cortisol

Regarding neuropeptides, Burbach (2011) reports:

We know neuropeptides now for over 40 years as chemical signals in the brain. The discovery of neuropeptides is founded on groundbreaking research in physiology, endocrinology, and biochemistry during the last century and has been built on three seminal notions: (1) peptide hormones are chemical signals in the endocrine system; (2) neurosecretion of peptides is a general principle in the nervous system; and (3) the nervous system is responsive to peptide signals. These historical lines have contributed to how neuropeptides can be defined today: “Neuropeptides are small proteinaceous substances produced and released by neurons through the regulated secretory route and acting on neural substrates.” Thus, neuropeptides are the most diverse class of signaling molecules in the brain engaged in many physiological functions. (p. 1)

Simply put, neuropeptides are the transmitters that allow the brain to communicate within itself and with the rest of the body’s functions. The increase or decrease of these neuropeptides/neurotransmitters alters human physiology (function) and any action upon the body that affects the neurotransmitters can either help normalize function or conversely destroy functioning with the human body.  This is the foundation of homeostasis and, therefore, if we can affect the function of neurotransmitters, then it is safe to say we can have a level of influence on homeostasis.  This obviously ties into our founder’s observations and the beginning of chiropractic! 

In an additional paper, Plaza-Manzano et al. (2014) wrote, “Several neuropeptides, such as neurotensin, oxytocin, or orexin A have been associated with hypoalgesia and pain modulation, and it is well known that cortisol plays an analgesic role related to stress responses. Recent theories have also suggested that chronic pain could be partly maintained by maladaptive physiological responses of the organism facing a recurrent stressor, a situation related to high cortisol levels” (p. 231). The authors continued by stating, “To make better therapeutic decisions, professionals would profit from knowing whether one type of SM (adjustment) is better than others in terms of antinociceptive (authors comment: antinociceptive = pain inhibition) effects (neurotensin, orexin A, oxytocin, and cortisol). Taking these data into account, our purpose was to determine whether cervical and thoracic manipulation would induce differences in neuropeptide production or have a similar biochemical response (Plaza-Manzano et al., 2014, p. 232).

Plaza-Manzano et al. (2014) went on to say “…within-group comparisons in cervical and thoracic manipulation groups showed a significant increase in neurotensin levels immediately post-intervention compared with pre-intervention levels… At the descriptive level, an important decrease in orexin A concentration was detected after the intervention in the thoracic SM (spinal manipulation) group in comparison with the control group… the cervical SM group showed increased oxytocin values when compared with the thoracic SM group immediately post-intervention (Plaza-Manzano et al., 2014, p. 234). At 2 hours after the intervention, an increase was found only in the cervical SM group when compared with pre-intervention levels… the cervical SM group showed a significant increase in cortisol plasma concentration immediately post-intervention compared with baseline values” (Plaza-Manzano et al. 2014, p. 235). 

Regarding pain Plaza-Manzano et al. (2014) stated:

It is well established that neurotensin affects the activity of oxytocin-positive cells in the supraoptic nucleus. Oxytocin is a nonapeptide that plays a major neuroendocrine role, modulating several physiological functions in mammals, like somatosensory transmission, nociception, and pain. Oxytocin is synthesized and secreted by a subpopulation of the paraventricular and supraoptic nuclei of the hypothalamus. In fact, several studies now support the idea that oxytocin exerts a potent antinociceptive control after its release in the spinal cord from hypothalamo-hypophysal descending projections (from the brain) … In studies involving human subjects, pain relief was reported in central neurogenic pain and in low back pain after the intracerebroventricular and intrathecal administration of oxytocin (aka pharmaceutical intervention). No previous study has evaluated whether SM has an effect on oxytocin plasmatic concentration. Our results suggest that the increase of the plasmatic concentration of oxytocin following an SM could be partly responsible for the analgesic effect linked to manual therapy techniques due to the activation of descending pain-inhibitory pathways. Orexins are known to be a hypothalamic peptide critical for feeding and normal wakefulness...Orexinergic projections were identified in periaqueductal gray matter, the rostral ventral medulla, the dorsal horn, and the dorsal root ganglion. Emerging evidence shows that the central nervous system administration (intracranial ventricle or intrathecal injection) of orexin A can suppress mechanical allodynia and thermal hypersensitivity in multiple pain models, suggesting the regulation of nociceptive processing via spinal and supraspinal mechanisms. In addition, orexins showed antinociceptive effects on models of pain, such as neuropathic pain, carrageenan test, and postoperative pain… Cortisol is therefore one of the biochemical factors delivered in stress situations that acts to decrease local edema and pain by blocking early stages of inflammation. In addition, it is also believed that high cortisol levels promote wound healing by stimulating gluconeogenesis. The response to stress is triggered by the stimulation of the hypothalamus-pituitary-adrenal axis. It has been proven that a subject’s level of stress can be correlated with secreted cortisol levels. (p. 236) 

The above study explains the neurochemical mechanism through which pain in mediated via the chiropractic spinal adjustment. Many of the pharmacological and nutraceutical interventions also target these systems through a variety of measures, some with significant negative side-effects.  Next, let’s examine what control these neuropeptides have in the human body beyond pain control. This will begin to explain the systemic connection with the chiropractic adjustment.

Systemic Effect of the Chiropractic Adjustment by Increasing of the NOC Axis

According to St-Gelais, Jomphe and Trudeau (2006), “…we focus our attention on the roles of NT [neurotensin] in the CNS. However, it is important to point out that this peptide is also highly expressed peripherally where it acts as a modulator of the gastrointestinal and cardiovascular systems” (p. 230). These authors discussed the role of antipsychotic drugs in cases of schizophrenia and how it was used to elevate the neurotensin level.  They found it would promote partial recovery while an additional study revealed that unmediated patients displayed a lowering of neurotensin.

An increase in neurotensin acts as a psychostimulant. A study conducted over the course of 25 years on individuals with drug abuse issues showed that increasing neurotensin levels decreased effects of psychostimulants such as amphetamines and cocaine. This study on drug addiction, according to St-Gelais et al. (2006), was conducted on animals, but there are many in chiropractic who have reported on a case-by-case basis that integrating chiropractic has helped many with drug abuse issues. Perhaps what this article suggests can help find more answers.

St-Gelais et al. (2006) also found a strong connection with a decrease in neurotensin in the following:

1. Schizophrenia
2. Gastrointestinal function
3. Cardiac function
4. Parkinson’s disease
5. Elevated blood pressure
6. Eating disorders
7. Cancer of the
   1. Colon
   2. Lungs
   3. Ovaries
   4. Pancreas
   5. Prostate
   6. Bones
   7. Brain
8. Alzheimer’s
9. Stroke (ischemic deaths)
10. Inflammation

Although the literature has not yet conclusively shown that any one of the central nervous system conditions are causally involved with the reduction of neurotensin, the literature strongly suggest that it plays a significant role. There is definitely a common denominator in neurotensin levels and these seemingly uncorrelated conditions.

Orexins, also known as hypocretins, according to Ebrahim, Howard, Kopelman, Sharief and Williams (2002) have an important role in sleep and (mental) arousal states. They state, “The hypocretins are thought to act primarily as excitatory neurotransmitters…suggesting a role for the hypocretins in various central nervous functions related to noradrenergic innervation, including vigilance, attention, learning, and memory. Their actions on serotonin, histamine, acetylcholine and dopamine neurotransmission is also thought to be excitatory and a facilitatory role on gamma-aminobutyric acid (GABA) and glutamate-mediated neurotransmission is suggested” (p. 227).

Ebrahim et al. (2002) continued:

Apart from their primary role in the control of sleep and arousal, the hypocretins have been implicated in multiple functions including feeding and energy regulation, neuroendocrine regulation, gastrointestinal and cardiovascular system control, the regulation of water balance, and the modulation of pain. A role in behaviour is also postulated. The cell bodies responsible for hypocretin synthesis are localized to the tuberal part of the hypothalamus, the so-called feeding centre...[which] has led to the suggestion that the hypocretins are mediators of energy metabolism. The neuroendocrine effects of the hypocretins include a lowering of plasma prolactin and growth hormone and an increase in the levels of corticotropin and cortisol, insulin and luteinizing hormone. Central administration of the hypocretins increases water consumption, stimulates gastric acid secretion and increases gut motility. The hypocretins increase mean arterial blood pressure and heart rate. The localization of long descending axonal projections containing hypocretin at all levels of the spinal cord suggests a role in the modulation of sensation and pain. Strong innervation of the caudal region of the sacral cord suggests a role in the regulation of both sympathetic and parasympathetic functions. (p. 227-228)

According to Lee, Macbeth, Pagani and Young (2009), oxytocin is a product of the hypothalamus and pituitary and according to Plaza-Manzano et al. (2014) it has been linked to the endogenous synthesis of opioids, thereby adding further explanation to the antinociceptive effects in the reduction of pain centrally. This partially explains the pain mechanism of the chiropractic adjustment.

For non-pain actions of oxytocin, beyond the actions of uterine contractions and lactation (You remember that board question, right?), Lee et al. (2009) reported that oxytocin is integral in:

1. Social memory
2. Social bonding
3. Parental behavior
4. Human behavior
5. Sexual behavior
6. Social behaviors (i.e. aggression)
7. Learning
8. Memory (overall)
9. Anxiety
10. Eating behavior
11. Sugar metabolism

Willenberg et al. (2000) reported, “Corticotropin-releasing hormone (CRH) and its receptors are widely expressed in the brain and peripheral tissues. This hormone is the principal regulator of the hypothalamic-pituitary-adrenal (HPA) axis and exerts its effects via two main receptor subtypes, type 1 (CRH-R1) and 2 (CRH-R2). CRH also activates both the adrenomedullary and systemic sympathetic system limbs and an intraadrenal CRH/ACTH/cortisol system…” (p. 137).

According to Smith and Vale (2006) “The principal effectors of the stress response are localized in the paraventricular nucleus (PVN) of the hypothalamus, the anterior lobe of the pituitary gland, and the adrenal gland. This collection of structures is commonly referred to as the hypothalamic-pituitary-adrenal (HPA) axis...In addition to the HPA axis, several other structures play important roles in the regulation of adaptive responses to stress. These include brain stem noradrenergic neurons, sympathetic adrenomedullary circuits, and parasympathetic systems” (pgs. 383-384) 

Smith and Vale (2006) also reported the following function of the HPA axis that has a direct control by corticotropin-releasing hormones:

1. Autonomic nervous system function
2. Learning
3. Memory
4. Feeding
5. Reproduction related behaviors
6. Metabolic changes
7. Cardiovascular regulation
8. Immune system

In addition, Willenberg et al. (2000) added the following”

1. Mental disorders
2. Depression
3. Schizophrenia

Conclusion

For over a century, chiropractic patients have been reporting the “miracles” of the results rendered in chiropractic offices worldwide and yet chiropractors have been persecuted and often vilified by the medical profession due to the lack of scientific evidence. Although this is a very broad perspective of the potential of the chiropractic care, it is now virtually impossible to ignore the fact that the chiropractic adjustment affects changes in neuropeptides in blood sample post-adjustment. These blood markers verify that changes are made in the human body and these changes have far reaching effects on both wellness and disease care. Medicine has been attempting to reproduce these effects via pharmaceutical intervention and a part of the solution now has to be chiropractic care based upon the evidence reported. 

This is just the beginning, as more evidence is needed to verify the full effects of the chiropractic spinal adjustment. We have a lot of work to do, but the scientific foundation of what chiropractors have observed since our beginning is getting stronger every month as more research is published.  

We would like to leave you with a last and seemingly unrelated statement.  We felt it was important to add this at the end since many of our critics negatively portray the safety of chiropractic care.  This statement shall put that to rest leaving only personal biases left standing. Whedon, Mackenzie, Phillips, and Lurie(2015) based their study on 6,669,603 subjects and after the unqualified subjects had been removed from the study, the total patient number accounted for 24,068,808 office visits. They concluded, “No mechanism by which SM [spinal manipulation] induces injury into normal healthy tissues has been identified”(Whedon et al., 2015, p. 5). This study supersedes all the rhetoric about chiropractic and stroke and renders an outcome assessment to help guide the triage pattern of mechanical spine patients.

References:

1. Reed, W. R., Pickar, J. G., Sozio, R. S., & Long, C. R. (2014). Effect of spinal manipulation thrust magnitude on trunk mechanical activation thresholds of lateral thalamic neurons.Journal of Manipulative and Physiological Therapeutics, 37(5), 277-286.

2. Gay, C. W., Robinson, M. E., George, S. Z., Perlstein, W. M., & Bishop, M. D. (2014). Immediate changes after manual therapy in resting-state functional connectivity as measured by functional magnetic resonance imaging in participants with induced low back pain.Journal of Manipulative and Physiological Therapeutics, 37(9), 614-627.

3. Burbach, J. P. (2011). What are neuropeptides? In J. Walker (Ed.),Methods in molecular biology (pp. 1-36). Clifton, New Jersey: Humana Press.

4. Plaza-Manzano, G., Molina-Ortega, F., Lomas-Vega, R., Martinez-Amat, A., Achalandabaso, A., & Hita-Contreras, F. (2014). Changes in biochemical markers of pain perception and stress response after spinal manipulation.Journal of Orthopedic and Sports Physical Therapy, 44(4), 231-239.

5. St-Gelais, F., Jomphe C., & Trudeau, L. (2006). The role of neurotensin in central nervous system pathophysiology: What is the evidence?Journal of Psychiatry & Neuroscience,31(4) 229-245.

6. Ebrahim, I. O., Howard, R. S., Kopelman, M. D., Sharief, M. K., & Williams, A. J. (2002). The hypocretin/orexin system.Journal of the Royal Society of Medicine,95(5), 227-230.

7. Lee, H. J., Macbeth, A. H., Pagani, J. H., & Young, W. S. (2009). Oxytocin: The great facilitator of life.Progressive Neurobiology, 88(2), 127-151.

8. Willenberg, H. S., Bornstein, S. R., Hiroi, N., Path, G., Goretzki, P. E., Scherbaum, W. A., & Chorusos, G. (2000). Effects of a novel corticotropin-releasing-hormone receptor type I antagonist on human adrenal function.Molecular Psychiatry, 5(2), 137-141.

9. Smith, S. M., & Vale, W. W. (2006). The role of hypothalamic-pituitary-adrenal axis neuroendocrine response to stress.Dialogue in Clinical Neuroscience, 8(4), 383-395.

10. Whedon, J. M., Mackenzie, T. A., Phillips, R. B., & Lurie, J. D. (2015). Risk of traumatic injury associated with chiropractic spinal manipulation in Medicare Part B beneficiaries aged 66-69 years. Spine, 40(4), 264-270.

Dr. Mark Studin is an Adjunct Associate Professor of Chiropractic at the University of Bridgeport College of Chiropractic, an Adjunct Professor of Clinical Sciences at Texas Chiropractic College and a clinical presenter for the State of New York at Buffalo, School of Medicine and Biomedical Sciences for post-doctoral education, teaching MRI spine interpretation, spinal biomechanical engineering and triaging trauma cases. He is also the president of the Academy of Chiropractic teaching doctors of chiropractic how to interface with the medical and legal communities (www.DoctorsPIProgram.com), teaches MRI interpretation and triaging trauma cases to doctors of all disciplines nationally and studies trends in healthcare on a national scale (www.TeachDoctors.com). He can be reached at DrMark@AcademyofChiropractic.com or at 631-786-4253.

Dr. Bill Owens is presently in private practice in Buffalo and Rochester NY and generates the majority of his new patient referrals directly from the primary care medical community.  He is an Associate Adjunct Professor at the State University of New York at Buffalo School of Medicine and Biomedical Sciences as well as the University of Bridgeport, College of Chiropractic and an Adjunct Professor of Clinical Sciences at Texas Chiropractic College.  He also works directly with doctors of chiropractic to help them build relationships with medical providers in their community. He can be reached at dr.owens@academyofchiropractic.com or www.mdreferralprogram.com or 716-228-3847  

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Chiropractic Linked to Increased Immunity

A report on the scientific literature 

By: Mark Studin DC, FASBE(C), DAAPM, DAAMLP

From the public’s perspective, we all want to be well and not sick. During the winter months we fear the flu and colds and according to American Public Media (2016) we spend over $40 billion dollars annually just to feel better. Whether that number is accurate, underinflated or overinflated, we can all agree that as a society we spend a significant amount of money just to feel better and not to actually be better. The new buzzword over the last decade has been “wellness” and even hospitals are touting to focus on wellness although most MD’s who staff those hospitals have little to no training in wellness vs. disease care.

Personally, I welcome those highly trained MD’s who focus on disease care and our society desperately needs every one of them who is helping to successfully treat sick patients. However, medicine has failed at the “wellness game” and we are starting to see “functional medicine” practitioners who use holistic measures such as vitamins, herb, minerals and other natural means and most are not doctors of medicine, but practitioners who understand that wellness does not necessitate the use of pharmaceuticals. The goal of wellness is to increase our immune system to increase our immunity to various viruses and bacterial causing diseases in part of an overall health plan.

According to Wikipedia (2016) “In biology,immunity is the balanced state of having adequate biological defenses to fighting infection,disease, or other unwanted biological invasion, while having adequatetoleranceto avoidallergy, andautoimmune diseases. It is the capability of the body to resist harmfulmicroorganismsorvirusesfrom entering it. Immunity involves both specific and nonspecific components. The nonspecific components act either as barriers or as eliminators of wide range of pathogens irrespective of antigenic specificity. Other components of theimmune systemadapt themselves to each new disease encountered and are able to generate pathogen-specific immunity.” (https://en.wikipedia.org/wiki/Immunity_(medical)

According to Jeffries (1991) “The relationship between adrenocortical function and immunity is a complex one. In addition to the well-known detrimental effects of large, pharmacologic dosages of glucocorticoids upon the immune process, there is impressive evidence that physiologic amounts of cortisol, the chief glucocorticoid normally produced by the human adrenal cortex, is necessary for the development and maintenance of normal immunity.” Although many scholarly articles explain the connection between cortisol and the immune system, The Adrenal Fatigue Solution (2016) articulates it well “The hormones produced by your adrenal glands, particularly the stress hormone cortisol, play an important role in regulating your immune system. If your cortisol levels go too low or too high, this can lead to regular infections, chronic inflammation, autoimmune diseases or allergies. Maintaining a balanced level of cortisol is an important part of staying healthy." (http://adrenalfatiguesolution.com/immune-system/)

One of cortisol’s many functions is to reduce inflammation. When your body encounters a pathogen, the immune system responds by quickly attacking it. This causes inflammation, which is often a good thing (it means the immune system is working). In those with healthy immune and endocrine systems, cortisol works to moderate the inflammation caused by an immune system response, but it does not completely eliminate it.”

Research done at the University of Madrid Medical School in Madrid Spain and the Department of Health Sciences at the University of Jaen Spain, Plaza-Manzano (2014) and fellow researchers found a link between immunity and chiropractic care. They were studying manipulation, or what chiropractors do when we adjust our patients and the cause for eradication of pain. They concluded that certain neuropeptides, or transmitters in the brain increase when our patients get adjusted. The specific neurotransmitter is called cortisol and according to Smith and Vale (2006) “The principal effectors of the stress response are localized in the paraventricular nucleus (PVN) of the hypothalamus, the anterior lobe of the pituitary gland, and the adrenal gland. This collection of structures is commonly referred to as the hypothalamic-pituitary-adrenal (HPA) axis...In addition to the HPA axis, several other structures play important roles in the regulation of adaptive responses to stress. These include brain stem noradrenergic neurons, sympathetic adrenomedullary circuits, and parasympathetic systems” (pgs. 383-384) . Smith and Vale also reported that balanced cortisol is important in the maintenance of the immune system.

It was reported that post-chiropractic adjustment (high velocity, low amplitude spinal manipulation: SM), at 2 hours after the intervention, an increase was found only in the cervical SM group when compared with pre-intervention levels… the cervical SM group showed a significant increase in cortisol plasma concentration immediately post-intervention compared with baseline values” (Plaza-Manzano et al. 2014, p. 235). This verifies that chiropractic care has a direct link to the cortisol-immunity connection through the neuro-endocrine reaction.

I would like to leave you with a last and seemingly unrelated statement. Our research team felt it is important to add this at the end since many of our critics negatively portray the safety of chiropractic care. This statement shall put that to rest leaving only personal biases left standing. Whedon, Mackenzie, Phillips, and Lurie(2015) based their study on 6,669,603 subjects and after the unqualified subjects had been removed from the study, the total patient number accounted for 24,068,808 office visits. They concluded, “No mechanism by which SM [spinal manipulation] induces injury into normal healthy tissues has been identified”(Whedon et al., 2015, p. 5). This study supersedes all the rhetoric about chiropractic and stroke and renders an outcome assessment to help guide the triage pattern of mechanical spine patients.

References:

1. The Cost of the Common Cold, American Public Media (2016), Retrieved from: http://www.marketplace.org/2011/01/21/life/cost-common-cold
2. Immunity (2016) Retrieved from: https://en.wikipedia.org/wiki/Immunity_(medical)
3. Jeffries W., (1991) Cortisol and Immunity, Medical Hypothesis, 34, 198-208
4. Adrenal Fatigue and Your Immune System (2016). Retrieved from: http://adrenalfatiguesolution.com/immune-system/
5. Plaza-Manzano, G., Molina-Ortega, F., Lomas-Vega, R., Martinez-Amat, A., Achalandabaso, A., & Hita-Contreras, F. (2014). Changes in biochemical markers of pain perception and stress response after spinal manipulation. Journal of Orthopedic and Sports Physical Therapy, 44(4), 231-239.
6. Smith, S. M., & Vale, W. W. (2006). The role of hypothalamic-pituitary-adrenal axis neuroendocrine response to stress. Dialogue in Clinical Neuroscience, 8(4), 383-395.
7. Whedon, J. M., Mackenzie, T. A., Phillips, R. B., & Lurie, J. D. (2015). Risk of traumatic injury associated with chiropractic spinal manipulation in Medicare Part B beneficiaries aged 66-69 years. Spine, 40(4), 264-270.

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Sleep Disorder Improvements

 Have Been Linked to Chiropractic Care

A report on the scientific literature 

By: Mark Studin DC, FASBE(C), DAAPM, DAAMLP

“A sleep disorder, or somnipathy, is a medical disorder of the sleep patterns of a person or animal. Some sleep disorders are serious enough to interfere with normal physical, mental, social and emotional functioning. Disruptions in sleep can be caused by a variety of issues, from teeth grinding (bruxism) to night terrors. When a person suffers from difficulty falling asleep and/or staying asleep with no obvious cause, it is referred to as insomnia.

Sleep disorders are broadly classified into dyssomnias, parasomnias, circadian rhythm sleep disorders involving the timing of sleep, and other disorders including ones caused by medical or psychological conditions and sleeping sickness. Some common sleep disorders include sleep apnea (stops in breathing during sleep), narcolepsy and hypersomnia (excessive sleepiness at inappropriate times), cataplexy (sudden and transient loss of muscle tone while awake), and sleeping sickness (disruption of sleep cycle due to infection). Other disorders include sleepwalking, night terrors and bed wetting. Management of sleep disturbances that are secondary to mental, medical, or substance abuse disorders should focus on the underlying conditions.” (retrieved from: https://en.wikipedia.org/wiki/Sleep_disorder)

According to the Centers for Disease Control and Prevention “Sleep is increasingly recognized as important to public health, with sleep insufficiency linked to motor vehicle crashes, industrial disasters, and medical and other occupational errors.Unintentionally falling asleep, nodding off while driving, and having difficulty performing daily tasks because of sleepiness all may contribute to these hazardous outcomes. Persons experiencing sleep insufficiency are also more likely to suffer from chronic diseases such as hypertension, diabetes, depression, and obesity, as well as from cancer, increased mortality, and reduced quality of life and productivity.¹ Sleep insufficiency may be caused by broad scale societal factors such as round-the-clock access to technology and work schedules, but sleep disorders such as insomnia or obstructive sleep apnea also play an important role.An estimated 50-70 million US adults have sleep or wakefulness disorder. Notably, snoring is a major indicator of obstructive sleep apnea.

According to SleepMed (2015):

Insomnia Statistics

Narcolepsy Statistics

Children & Sleep Statistics

Women & Sleep Statistics

Older Adult Statistics

General Statistics

Research done at the University of Madrid Medical School in Madrid Spain and the Department of Health Sciences at the University of Jaen Spain, Plaza-Manzano (2014) and fellow researchers found a link between sleep disorders and chiropractic care. They were studying manipulation, or what chiropractors do when we adjust our patients and the cause for eradication of pain. They concluded that certain neuropeptides, or transmitters in the brain increase when our patients get adjusted. The specific neurotransmitter is called Orexin and is commonly known in medical terms as hypocretins.

According to Ebrahim (2002) and fellow researchers “have an important role in sleep and (mental) arousal states. They state, “The hypocretins are thought to act primarily as excitatory neurotransmitters…suggesting a role for the hypocretins in various central nervous functions related to noradrenergic innervation, including vigilance, attention, learning, and memory. Their actions on serotonin, histamine, acetylcholine and dopamine neurotransmission is also thought to be excitatory and a facilitatory role on gamma-aminobutyric acid (GABA) and glutamate-mediated neurotransmission is suggested” (p. 227). If we focus simply on serotonin, that is responsible for mood, appetite and sleep and regarding the latter effects many sleep patterns if imbalanced or depleted.

A chiropractic adjustment has proven to increase the orexin or hypocretins in the human body, which has a direct effect on the production of serotonin in the human body. Serotonin has been known for many years and recognized in the scientific literature for playing a role in the modulation of sleep.  Although more research is still needed to quantify the results, this now gives a verified scientific explanation to the results chiropractic patients have been experiencing over the last century.

As with all of my articles from here forward, I would like to leave you with a last and seemingly unrelated statement.  I felt it was important to add this at the end since many of our critics negatively portray the safety of chiropractic care.  This statement shall put that to rest leaving only personal biases left standing.  Whedon, Mackenzie, Phillips, and Lurie(2015) based their study on 6,669,603 subjects and after the unqualified subjects had been removed from the study, the total patient number accounted for 24,068,808 office visits. They concluded, “No mechanism by which SM [spinal manipulation] induces injury into normal healthy tissues has been identified”(Whedon et al., 2015, p. 5). This study supersedes all the rhetoric about chiropractic and stroke and renders an outcome assessment to help guide the triage pattern of mechanical spine patients.

References:

1. Sleep Disorder (October 2015), Retrieved from: https://en.wikipedia.org/wiki/Sleep_disorder
2. Insufficient Sleep is a Public Health Problem (September 2015) Retrieved from: http://www.cdc.gov/features/dssleep/
3. Sleep Statistics, (2016), retrieved from: http://www.sleepmedsite.com/page/sb/sleep_disorders/sleep_statistics
4. Plaza-Manzano, G., Molina-Ortega, F., Lomas-Vega, R., Martinez-Amat, A., Achalandabaso, A., & Hita-Contreras, F. (2014). Changes in biochemical markers of pain perception and stress response after spinal manipulation. Journal of Orthopedic and Sports Physical Therapy, 44(4), 231-239.
5. Ebrahim, I. O., Howard, R. S., Kopelman, M. D., Sharief, M. K., & Williams, A. J. (2002). The hypocretin/orexin system. Journal of the Royal Society of Medicine, 95(5), 227-230.
6. Whedon, J. M., Mackenzie, T. A., Phillips, R. B., & Lurie, J. D. (2015). Risk of traumatic injury associated with chiropractic spinal manipulation in Medicare Part B beneficiaries aged 66-69 years. Spine, 40(4), 264-270.

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Chiropractic Spinal Adjustments,

 Changes in Organ Systems

& Treatment of Disease

A literature review and report on the positive effects of chiropractic on the autonomic nervous system, heart function and the circulatory system

A report on the scientific literature 

By: Mark Studin DC, FASBE(C), DAAPM, DAAMLP

William Owens DC, DAAMLP

Citation: Studin M., Owens W., (2015) Chiropractic Spinal Adjustments, Changes in Organ Systems and Treatment of Disease, The American Chiropractor, 38(11) 20, 22-25

A report on the scientific literature 

The autonomic nervous system is the part of the nervous system that supplies the internal organs, including the blood vessels, stomach, intestine, liver, kidneys, bladder, genitals, lungs, pupils, heart, and sweat, salivary, and digestive glands.

The autonomic nervous system has two main divisions:

• Sympathetic
• Parasympathetic

After the autonomic nervous system receives information about the body and external environment, it responds by stimulating body processes, usually through the sympathetic division, or inhibiting them, primarily through the parasympathetic division. The autonomic nerve pathway involves two nerve cells. One cell is located in the brain stem or spinal cord and is connected by nerve fibers to the other cell, which is located in a cluster of nerve cells (called an autonomic ganglion). Nerve fibers from these ganglia connect with internal organs. Most of the ganglia for the sympathetic division are located just outside the spinal cord on both sides of it. The ganglia for the parasympathetic division are located near or in the organs they connect with.

The autonomic nervous system controls many internal body processes such as the following:

• Blood pressure
• Heart and breathing rates
• Body temperature
• Digestion
• Metabolism (thus affecting body weight)
• The balance of water and electrolytes (such as sodium and calcium)
• The production of body fluids (saliva, sweat, and tears)
• Urination
• Defecation
• Sexual response

Many organs are controlled primarily by either the sympathetic or the parasympathetic division. Sometimes the two divisions have opposite effects on the same organ. For example, the sympathetic division increases blood pressure, and the parasympathetic division decreases it. Overall, the two divisions work together to ensure that the body responds appropriately to different situations. (Low, 2015, http://www.merckmanuals.com/home/brain-spinal-cord-and-nerve-disorders/autonomic-nervous-system-disorders/overview-of-the-autonomic-nervous-system)

As you can see by the above definition, the human body is in large part controlled by autonomic or automatic nerves, the kind that function without your control. The question that has arisen throughout the years in chiropractic is, “Can the chiropractic spinal adjustment have an effect on those nerves and with that, can disease process or pathology be influenced? The question of the chiropractic spinal adjustment positively effecting pain through the brain connection (central nervous system) has already been conclusively established.

As reported these authors in 2015, the chiropractic adjustment produces direct and measureable effects on the central nervous system across multiple regions which is responsible for the processing of emotion (cingulate cortex, aka limbic cortex) and the insular cortex, which is also responsible for regulating emotion as well as homeostasis. The motor cortex is involved in the planning and execution of voluntary movements, the amygdala’s primary function is memory and decision making (also part of the limbic system), the somatosensory cortex is involved in processing the sense of touch (remember the homunculus) and, finally, the periaqueductal gray is responsible for descending pain modulation (the brain regulating the processing of painful stimuli).

The next question then becomes, “Can the chiropractic adjustment cause the central nervous system to effectuate changes in those systems that regulate our organs through the autonomic nervous system?” When studying the autonomic nervous system, according to Welch and Boone (2008), “Because of the proximity of the upper cervical vertebrae to the brainstem, parasympathetic influences dominate these segmental levels; and therefore, a cervical adjustment could likely result in a parasympathetic response (slowing down of heart beat, lowering of BP, constriction of pupils). In those spinal regions where sympathetic innervation is substantial (upper thoracic and upper lumbar), a chiropractic adjustment could elicit a sympathetic response (stimulation of heart beat, raising of BP, dilation of pupils” (p. 87).

In this study, the findings after a cervical adjustment were linked to an increase in parasympathetic dominance. This was apparent when observing the changes occurring in pre- to post-adjustment HRV [heart rate variability] total power that reflects the balance between LF [low frequency] (ie, sympathetic tone) and HF [high frequency] (e, parasympathetic tone). It was evident that, in each patient, the pre- to post-adjustment decrease in LF/HF [low frequency/high frequency] was due to either a larger increase in parasympathetic activity or a lesser decrease in parasympathetic activity when compared with sympathetic activity. These findings are consistent with other studies that have linked upper cervical chiropractic adjustments to parasympathetic mediated regulatory systems.

Among those individuals receiving thoracic adjustments, the findings indicated that the responses were sympathetic in nature…Heart rate variability data revealed that total power, which is a measure of total autonomic signal, decreased substantially post-adjustment. When considering the balance between parasympathetic/sympathetic activity (LH/HF) [low frequency/ high frequency], it was evident that, in each patient, the pre- to post-adjustment decrease in LH/HF [low frequency/high frequency] was due to either a larger increase in sympathetic activity or a lesser decrease in sympathetic activity when compared with parasympathetic activity. These findings are consistent with other studies that have linked thoracic chiropractic adjustments to sympathetic mediated regulatory systems.” (p. 90-91).

Budgell and Hirano (2001) reported, “…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 cavitation 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” (p. 98).

Budgell and Polus reported in The Journal of Manipulative and Physiological Therapeutics (2006) that chiropractic adjustments of the thoracic spine were associated with significant heart rate values and influenced the autonomic output of the heart, meaning that the heart rate generally lowers with the chiropractic adjustment because of the shift in the neurological communication of the autonomic nervous system (to the parasympathetic nerves) causing the heart to slow or normalize. This study by Budgell and Polus offers potential answers to many as to why patients' heart rates spike for no apparent reason. The spine, although a great influence to the nervous system, has often been overlooked in the clinical arena as the prime cause for cardiac issues. The authors of this article want to emphasize that chiropractic care has a positive effect for many conditions, including cardiac, and should be consideredin conjunction with necessary treatment from all other health care specialists, as clinically indicated, in order to make a conclusive diagnosis to rule out life-threatening illnesses.

Ward, Coats, Tyer, Weigand, and Williams (2013), found that in an upper thoracic manipulation (mobilization) of the thoracic spine, “There was no statistically significant or clinically relevant difference found between groups for any of the cardiovascular measurements at any time point” (p. 107). This study would appear to overturn the previous findings of autonomic change as a sequella to a chiropractic adjustment. However, if you look carefully at the study limitations, you will realize that this study strongly suggests that chiropractic has perhaps the “only solution” to effect autonomic changes. 

Ward et al. (2013) included the following points under the heading “Study Limitations.” “The population that we sampled was composed of chiropractic students who regularly receive spinal manipulation. It is possible that the general public who do not receive regular chiropractic manipulation may react differently than individuals who receive spinal manipulation more frequently. In our design, we did not attempt to exclusively manipulate fixated segments of the upper thoracic spine. It may be argued that, if a patient had a painful fixated spinal segment that was manipulated, the results of this study may have been different…Last, our study participants were young and relatively normotensive” (p. 108-109).

The limitations also suggest that the treatment rendered was a joint mobilization, similar to what physical therapy is designed to do and not a chiropractic spinal adjustment. There were no fixations, and a as result, no negative neurological sequelae. In addition, this study was performed on young, healthy chiropractic students who have been getting chiropractic adjustments on a regular basis, probably removing any aberrant neurological issues prior to this study. It is highly unlikely there were significant biomechanical alterations in this study population again, due to age and frequency of chiropractic care. 

Additionally, the lead author of this article, over the course of 5 years in private practice, did pre- and post-extremity Doppler studies on a “sick” population that was not receiving any chiropractic care and observed the same results as Welch and Boone stated above. In addition, Ward et al. (2013) appear to have validated why a chiropractic adjustment on a historical “chiropractic subluxated” region must be “adjusted chiropractically” to have the benefit of autonomic changes. It is the chiropractic “diagnosis” of the functional spinal biomechanical abnormality that is the expertise of the doctor of chiropractic, not simply the act of the therapeutic adjustment to treat neuromuscular negatively affected regions and not simply mobilize segments. 

Chronic pain patients were studied by Kang, Chen, Chen and Jaw (2012). Their focus was on the following: sleep disorders, pain scales, pressure pain thresholds, disability indexes and heart rate variability analysis. Although these authors have touched on many areas that have been reported to have a positive influence by chiropractic care, for the purpose of this review we are focusing on heart rate variability. Kang et al. (2012) reported, “Heart rate variability (HRV) analysis, initially developed to evaluate the prognosis of cardiac diseases, has been utilized to assess autonomic functions in chronic pain conditions…The autonomic nervous system plays an important role in the pathogenesis of chronic muscle pain. The autonomic dysfunction in fibromyalgia is characterized by persistent autonomic hyperactivity at rest and hypo-reactivity during stress. In addition, HRV analysis in patients with chronic low back pain has shown that a greater level of disability is associated with a lower HRV” (p. 797). They continued, “Our results are similar to a previous study demonstrating that in participants with chronic low back pain, decreased HRV is significantly associated with a higher index of perceived disability but not with pain intensity itself…It has long been postulated that autonomic regulatory dysfunction is involved in the pathogenesis of several chronic pain conditions” (Kang et al., 2012, p. 801). They concluded, “…reduced HRV was associated with subjective disability in patients with chronic neck pain” (Kang et al., 2012, p. 802).

Kang et al. (2012) stated, “The pathologic mechanism of chronic neck pain is still not understood and is a multifactorial disease… Chronic neck pain is difficult to treat. Treatment options must include multimodal, interventions combining physical agents, oral medications, local injections, and adequate exercise” (p. 800). This prevailing message perpetuates previous reports in the literature and further solidifies that allopathy has no solutions for mechanical cervical spine chronic pain. Apkarian ET. Al. (2004) reported that “Ten percent of adults suffer from severe chronic pain. Back problems constitute 25% of all disabling occupational injuries and are the fifth most common reason for visits to the clinic; in 85% of such conditions, no definitive diagnosis can be made.” (pg. 10410) Apkarian, Hashmi, and Baliki (2011) reported “Clinically, the most relevant conditions in which human brain imaging can have a substantial impact are chronic conditions, as they remain most poorly understood and minimally treatable by existing [medical] therapies” (p. S53).” In essence, what these authors are stating is that although many people suffer from chronic spine pain, very few of them are actually diagnosed with a “medical condition,” aka an “anatomical” lesion.  The chiropractic profession has long professed the lesion is actually functional and based on aberrant spinal biomechanics (subluxation) or mechanical spine pain (no fracture, tumor or infection). That, in fact, is what places chiropractic in the unique role in the diagnosis and management of biomechanical spine pain.  When we lead with “chiropractic spinal assessment,” we have no competition in medicine or rehabilitation.

Peterson, Bolton, and Humphreys (2012) “…investigate[d] outcomes and prognostic factors in patients with acute or chronic low back pain (LBP) undergoing chiropractic treatment” (p. 525). In chronic LBP, recent studies indicate that significant improvement is often fairly rapid, usually by the fourth visit, and that patients initially receiving treatment 3 to 4 times a week have better outcomes” (Peterson et al., 2012, p. 526). “Patients with chronic and acute back pain both reported good outcomes, and most patients with radiculopathy (neurogenic) also improved” (Peterson et al., 2012, p. 525). “At 3 months…69% of patients with chronic pain stated that they were either much better or better” (Peterson et al., 2012, p. 538). This is unlikely to be due to the natural history of low back pain because these patients have already passed the period when natural history occurs.

A study by Tamcan et al. (2010) was the only population-based study of the so called “natural history” of lower back pain and the authors found the “natural history” of chronic lower back pain was not ending in resolution of symptoms, but instead they documented patients moving “in and out” of a level of pain they could tolerate.   Based on the only population-based study of chronic lower back pain, the idea that the natural history of lower back pain ends with a resolution of symptoms is completely false and something that is merely perpetuated by our present healthcare system.

Lawrence et al. (2008) reported, “Existing research evidence regarding the usefulness of spinal adjusting… indicates the following…1. As much or more evidence exists for the use of SMT [spinal manipulation] to reduce symptoms and improve function in patients with chronic LBP as for use in acute and subacute LBP” (p. 670). “…the manual therapy group showed significantly greater improvements than did the exercise group for all outcomes. Results were consistent for both the short-term and the long-term” (Lawrence et al., 2008, p. 663). We see in this study, as in others, that biomechanical alterations in the human spine, aka spinal subluxation, must be diagnosed and treated. They cannot simply be exercised or mobilized away.  This is the unique domain of the doctor of chiropractic. 

Dunn, Green, Formolo, and Chicoine  (2011) reported, “The clinical outcomes achieved for this sample should be considered within the context of this veteran patient base, which is typically represented by older, white males with multiple comorbidities. A high percentage of overall service-connected disability was noted, with only a small percentage associated with the low back region. Considerable psychological comorbidity was found, with a high prevalence of PTSD [post-traumatic stress disorder] and depression diagnoses. PTSD and chronic pain tend to co-occur and may interact in a way that can negatively affect either disorder. A previous retrospective study of chiropractic management for neck and back pain demonstrated less improvement among those with PTSD. These points are significant because severe comorbidities and psychosocial factors lessen the likelihood of obtaining positive outcomes with conservative measures, including SMT [chiropractic adjustments], for chronic LBP [low back pain]. Mean percentages of clinical improvement exceeded the MCID [minimum clinically important difference], despite the levels of service-connected disability and comorbidity among this sample of veteran patients” (pg. 930). They went on to conclude that in spite of significant comorbidities that historically compromise positive results, 60.2% of patients met or exceeded the minimum clinically important difference for improvement.

The above studies verify that allopathy cannot conclude an accurate diagnosis for chronic back or neck pain while chiropractic reportedly helps resolve these issues 69% of the time as reported in the literature. The authors of this paper have currently practiced for a combined 52 years and can confirm, based upon our observations in the private practice setting, that the percentage is closer to 95% for resolving mechanical spine pain. Although this is an observation and could appear unusually high, that is an accurate accounting of both our experience and that of many other practicing chiropractors who we have informally polled. 

Therefore, the above studies, excluding Ward et al. (2013), strongly, suggest that the autonomic nervous system has a direct cause and effect relationship with the chiropractic spinal adjustment and verifies another central nervous system connection. They also verify that chiropractic has demonstrated solutions in today’s healthcare system that can help prevent autonomic aberrant effects of chronic pain on heart rate variability and other related disabilities where allopathy has failed.  

When we consider disease care, it is critical to consider the autonomic connection and the effect of chiropractic care as that is part of the equation for scientifically validating many observational conclusions that doctors of chiropractic have realized in their offices over the last century. In addition, this and other central nervous system connection show promising results as the foundation for determining how organs and disease react to the chiropractic spinal adjustment. Although the literature does confirm this hypothesis, it is based on millions getting well observationally and science simply needed time to catch up. Although we now are beginning to realize many answers there is still quite a way to go in our understanding… but we are just that much closer with understating more of the adjustment-central nervous system-autonomic nervous system-disease connection.

References:

1. Low, P. (2015). Overview of the autonomic nervous system. Merck Manual Consumer Version, Retrieved from http://www.merckmanuals.com/home/brain-spinal-cord-and-nerve-disorders/autonomic-nervous-system-disorders/overview-of-the-autonomic-nervous-system

2. Studin, M., & Owens W. (2015). Research proves chiropractic adjustments effect emotions, learning, memory, consciousness, motivation, homeostasis, perception, motor control, self-awareness, cognitive function, voluntary movement, decision making, touch and pain: BRAIN CONNECTION. US Chiropractic Directory. Retrieved from http://uschirodirectory.com/research/item/744-research-proves-chiropractic-adjustments-effect-emotions,-learning,-memory,-consciousness,-motivation,-homeostasis,-perception,-motor-control,-self-awareness,-cognitive-function,-voluntary-movement,-decision-making,-touch-and-pain.html

3. Welch, A., & Boone, R. (2008). Sympathetic and parasympathetic responses to specific diversified adjustments to chiropractic vertebral subluxations of the cervical and thoracic spine. Journal of Chiropractic Medicine, 7(3), 86-93.

4. Budgell, B., & Hirano, F. (2001). Innocuous mechanical stimulation of the neck and alteration in heart-rate variability in healthy young adults. Autonomic Neuroscience: Basic and Clinical 91(1-2), 96-99.

5. Budgell, B., & Polus, B. (2006). The effects of thoracic manipulation on heart rate variability: A controlled crossover trial.Journal of Manipulative and Physiological Therapeutics, 29(8), 603-610.

6. Ward, J., Coats J., Tyer, K., Weigand, S., Williams, G. (2013). Immediate effects of anterior upper thoracic spine manipulation on cardiovascular response. Journal of Manipulative and Physiological Therapeutics, 36(2), 101-110.

7 Kang, J. H., Chen, H. S., Chen, S. C., & Jaw, F. S. (2012). Disability in patients with chronic neck pain, Heart rate variability analysis and cluster analysis. Clinical Journal of Pain, 28(9), 797-803.

8. Apkarian V., Sosa Y., Sonty S., Levy R., Harden N., Parrish T., Gitelman D., (2004) Chronic Back Pain Is Associated with Decreased Prefrontal and Thalamic Gray Matter Density, The Journal of Neuroscience, 24(46) 10410-10415

Apkarian, A. V., Hashmi, J. A., & Baliki, M. N. (2011). Pain and the brain: Specificity and plasticity of the brain in clinical chronic pain. Pain, 152(Suppl. 3), S49-S64.

9. Peterson, C. K., Bolton, J., & Humphreys, B. K. (2012). Predictors of improvement in patients with acute and chronic low back pain undergoing chiropractic treatment. Journal of Manipulative and Physiological Therapeutics, 35(7) 525-533.

10. Tamcan, O., Mannion, A. F., Eisenring, C., Horisberger, B., Elfering, A., & Müller, U. (2010). The course of chronic and recurrent low back pain in the general population. Pain, 150(3), 451-457.

11. Lawrence, D. J., Meeker, W., Branson, R., Bronford, G., Cates, J. R., Haas, M., Hawk, C. (2008). Chiropractic management of low back pain and low back-related leg complaints: A literature synthesis. Journal of Manipulative and Physiological Therapeutics, 31(9), 659-674.

12.  Dunn, A. S., Green, B. N., Formolo, L. R., & Chicoine, D. (2011). Retrospective case series of clinical outcomes associated with chiropractic management for veterans with low back pain. Journal of Rehabilitation Research & Development, 48(8), 927-934.

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