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

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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 



 William J. Owens DC, DAAMLP


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). 







Cervical Adjustment

Increased levels

Not reported

Increased levels

Increased levels

Thoracic Adjustment

Increased levels

Increased levels

No Change

Significant Decrease at

2 hours



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




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.


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 (, teaches MRI interpretation and triaging trauma cases to doctors of all disciplines nationally and studies trends in healthcare on a national scale ( He can be reached at 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 or or 716-228-3847  

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