Immune Responses to Spinal Manipulation

By Malik Slosberg, DC, MS

For many years, chiropractors have observed in their own practices that their patients sometimes demonstrate improvements of complaints related to immune problems: the disappearance or lessening of allergy symptoms, quicker recovery from or less frequent and severe colds and other respiratory infections, and so on.

In some large studies, it has been found that chiropractic care for nonmusculoskeletal conditions is only weakly to moderately successful, but rarely harmful^1-2 The most recent and thorough systematic literature review found that the evidence for effectiveness of spinal manipulation was inconclusive for nonmusculoskeletal conditions.³

Despite the lack of evidence of clinical effectiveness for nonmusculoskeletal conditions, a series of recent studies from several international research groups is systematically building the case that spinal manipulation appears to reduce the production of pro-inflammatory cytokines and increase the blood levels of immunoregulatory cytokines. Cytokines are small cell-signaling protein molecules that are secreted by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication.

The accumulation of data from these studies suggests that a possible benefit of spinal manipulation is related to neuroimmunological effects. Of course, this is an exciting proposition for clinicians who have seen such changes in their own patients. Let's review some of the research exploring the connections between spinal manipulation and functional changes in the immune system.

Early Research on Manipulation and the Immune System

Research in the 1990s laid the groundwork for the more recent papers published in the past five years. Brennan, et al.,⁴ published a paper demonstrating that upper thoracic spinal manipulation resulted in markers indicating significant increased phagocytic activity of neutrophils and monocytes compared to a sham manipulation or soft-tissue treatment. The findings suggest that a certain force threshold was needed to elicit the response.

In a second study, Brennan, et al.,⁵ concluded that their data suggests spinal manipulation, which generates a force over a certain threshold, elicits viscerosomatic responses that affect both neutrophils and mononuclear cells phagocytic activity, at least over the short term. And in a very small 1994 study,⁶ the study authors concluded that upper cervical adjustments increased CD4 "helper" T-cell counts, which initiate the body's response to viruses in HIV-positive subjects, by 48 percent over the six-month duration of the study.

Neural immunoregulation: Communication Between the Immune and Nervous Systems

These earlier papers have now been followed-up by a series of recent studies within the past five years. Teodorczyk-Injeyan, et al.,⁷ described the interplay between the nervous system and immune system as neural immunoregulation. The authors note that immune homeostasis is based on the reciprocal communication between the immune and the nervous systems executed by the actions of cytokines and neurotransmitters. In addition, the paper explains the close association of autonomic nerve terminals with macrophages and lymphocytes, which facilitates a chemically mediated transmission between nerves and immune cells.

This research group has published a series of papers that explores the relationship of spinal manipulation, spinoautonomic reflexes and their influence on activity of cells involved in immune and/or inflammatory responses. These interconnections may have great clinical relevance because studies⁸ on the pathophysiology of discogenic low back pain, sciatica, and ligamentous tissue damage-related pain⁹ reveal that the production of pro-inflammatory mediators, such as tumor necrosis factor alpha (TNF-a) and interleukin-1 beta (IL-1ß), are major factors in the genesis of pain and functional changes in neural activity. Furthermore, studies of the hypoalgesic effects of spinal manipulation have already been reported in the literature, suggesting that an anti-inflammatory mechanism might be activated by spinal manipulation.^10-11 Recent clinical studies have shown that chemical blockage of TNF-a is highly effective in reducing sciatic pain.¹²

Reduced Pro-Inflammatory Cytokines After Spinal Manipulation

In the first of their studies, the authors report that a single bilateral hypothenar upper-thoracic HVLA thrust resulted in the reduction of in vitro inflammatory cytokines, TNF-aand IL-1ß in blood samples activated with lipopolysaccharide taken before, 20 minutes and two hours after spinal manipulation. TNF-a and IL-1ß significantly declined in asymptomatic subjects assigned to manipulation with cavitation/audible, whereas in the sham and control groups, TNF-a and IL-1ß levels increased significantly after exposure to lipopolysaccharide.

The paper's conclusion states that manipulation-related down-regulation of inflammatory-type responses occurred via an unknown central mechanism. These findings suggest that a single thoracic manipulation effectively ameliorates the physiological responses of blood cells to an inflammatory stimulus and that spinovisceral reflex effects may alter the functional activity of cells in the immune and/or inflammatory systems. Based on these findings, the paper notes that spinal manipulation is likely to present a noninvasive and efficacious alternative to drug therapies for reducing inflammation and resultant pain.

A 2009 paper from the Hungarian National Institute for Rheumatology and Physiotherapy¹³ reported a dramatic and significant reduction in both debilitating cervicogenic headaches (before treatment 3-6 times a week lasting a total of 31-36 hours a week), neck stiffness and TNF-a after manual therapy in two women who suffered post-whiplash, MRI-documented C4-5 disc herniation.

Previous trials of conservative care (analgesic infusions, physical therapy) had failed. Both patients, after a neurological consult, were recommended to have a discectomy, but both opted for a trial of manual therapy (two times a week for 4-8 weeks) first. After manual therapy, surgery was unnecessary because both women became headache-free with a normal range of cervical motion. In addition, both patients experienced a dramatic reduction in TNF-a (reduced by more than half).¹³

The medical researchers conclude that pro-inflammatory substances secreted by the nucleus pulposus are likely involved in symp-tomatic disc herniation. In addition, TNF-a, interleukin-1ß and interleukin-10 may be involved in the pathogenesis of migraine at-tacks. After restoring spinal segmental motion and reducing pathologic mechanical irritation/compression, TNF-a levels were mark-edly reduced and symptoms were eliminated. In 2010, Roy,¹⁴ et al., followed up these two studies by evaluating pre- and post-intervention measures from blood samples detecting pro-inflammatory cytokines interleukin 6 (IL-6) and C-reactive protein (CRP) after a series of nine chiropractic manipulations from T12-L5 using the an adjusting instrument and related protocol in 10 chronic low back pain patients and 10 healthy subjects. Once again, the introduction notes that low back pain is often associated with an inflammatory process and increased production of several pro-inflammatory cytokines including IL-6 and CRP. IL-6 is the main mediator of the acute phase of pro-inflammatory cytokines and results in a marked increase in liver cell synthesis of CRP.

This trial found that a series of nine thoracic manipulations resulted in a reduction of both IL-6 and CRP; that is, a normalization response. Both IL-6 and CRP levels were reduced toward the values in the healthy subjects. IL-6 and CRP were elevated in chronic LBP patients pre-intervention, but post-intervention differences were smaller, suggesting that nine manipulations are capable of attenuating the inflammatory response. The authors opine that it is plausible the inflammatory process was being reversed in those who received the adjustments.

Immunoregulation, Interleukin 2 and Spinal Manipulation

Another related avenue of research on neural immunoregulation evaluates the effects of spinal manipulation on the production of interleukin 2 (IL-2) – an immunoregulatory (not pro-inflammatory) cytokine and signaling molecule, instrumental in the body's response to microbial infection and for the body's ability to discriminate between foreign (non-self) and self. IL-2 is a pivotal cytokine in T-cell-dependent immune responses and plays a major role in the development, maintenance and survival of regulatory T cells. Thus, it is of critical importance in induction and sustenance of immune tolerance.

Seventy-six asymptomatic subjects¹⁵ were randomized to receive an upper thoracic manipulation with cavitation or without cavitation, or were included in a control group. All subjects had their blood drawn before, 20 minutes and two hours after the intervention. Production of IL-2 in mononuclear cell cultures was activated with staphylococcal protein A (SPA). Induced secretion of IL-2 increased significantly in manipulation with and without cavitation. The paper concludes that in vitro T lymphocyte response to a SPA stimulus became enhanced after spinal manipulation. Therefore, this effect may be independent of joint cavitation/audible. This finding suggests manipulation may influence IL-2 immune-regulated biological responses.

In 2010, Teodorczyk-Injeyan, et al.,¹⁶ continued with this research on induction and regulation of immune responses related to interactions between the immune and nervous systems mediated by actions of neurotransmitters and immunoregulatory cytokines. To this end, the researchers followed the subjects from the previous study to determine if the increased production of interleukin-2 as a result of a single thoracic manipulation is associated with increased antibody synthesis from monocytes.

The paper reports that there were indeed significantly increased synthesis of immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies induced in cultures of peripheral blood mononuclear cells in subjects who received thoracic manipulation, particularly in those who had an associated cavitation. The paper concludes that antibody synthesis (IgG and IgM) induced by interleukin-2 can be, at least temporarily, increased after manipulation. This is additional direct evidence that thoracic manipulation may influence interleukin-2 immune-regulated biological responses.

The Take-Home Message

The studies described above demonstrate an accumulation of evidence that indicates spinal manipulation may influence the immune system's response to various stimuli. Three of the studies suggest that manipulation consistently reduced the production of pro-inflammatory mediators associated with tissue damage and pain from articular structures. Two studies provide evidence that manipula tion consistently reduced the production of pro-inflammatory mediators associated with tissue damage and pain from articular structures. Two studies provide evidence that manipulation may induce and enhance production of the immunoregulatory cytokine IL-2 and the production of immunoglobulins as well.

We must acknowledge that these results are preliminary because most are performed on asymptomatic subjects and the duration of the effects so far have only been demonstrated to be short-lived. Nevertheless, this research opens the door to further exploration of the possible neuroimmunoregulatory effects of spinal manipulation and confirms what many of us have observed in practice: Adjustments reduce pain and inflammation, and may improve immunoregulatory function.

References

1. Leboeuf-Yde C, et al. Self-reported nonmusculoskeletal responses to chiropractic intervention: a multination survey. JMPT, 2005;28(5):294-302.
2. Leboeuf-Yde C, et al. The types and frequencies of improved nonmusculoskeletal symptoms reported after chiropractic SMT. JMPT, 1999;22(9):559-64.
3. Bronfort G, Haas M, Evans R, Leiniger B, Triano J. Effectiveness of manual therapies: the UK evidence report. Chiropr Osteopat, 2010;18:3.
4. Brennan PC, et al. Enhanced phagocytic cell respiratory burst induced by spinal manipulation: potential role of substance P. JMPT, 1991;14:399-408.
5. Brennan PC, et al. Enhanced neurtophil respiratory burst as a biological marker for manipulation forces: duration of the effect and association with substance P and tumor necrosis factor. JMPT,1992;15:83-9.
6. Selano JL. The effects of specific upper cervical adjustments on the CD4 counts of HIV positive patients. Chiro Res J, 1994;3:32-9.
7. Teodorczyk-Injeyan JA, et al. SMT reduces inflammatory cytokines but not substance P production in normal subjects. JMPT, 2006;29:14-21.
8. Fiorentino PM, Tallents RH, Miller J-nH. Spinal interleukin-1B in a mouse model of arthritis and joint pain. Arthritis Rheum, 2008;58:3100-9.
9. King K, Davidson B, Zhou BE, Lu Y, Solomonow M. High magnitude cyclic load triggers inflammatory response in lumbar ligaments. Clin Biomech, 2009;25:792-98.
10. Terrett Ac VH. Manipulation and pain tolerance. Am J Phy Med, 1984;63:217-25.
11. Giles LG, Muller R. Chronic spinal pain: a randomized clinical trial comparing medication, acupuncture, and spinal manipulation. Spine, 2003;28:1490-502.
12. Mohammadian P, Gonsalves A, Tsai C, Hummel T, Carpenter T. Areas of capsaicin-induced secondary hyperalgesia and allodynia are reduced by a single chiropractic adjustment: a preliminary study. JMPT, 2004;27:381-7.
13. Omos G, MD, et al. Reduction in high blood TNF-a levels after manipulative therapy in 2 cervicogenic headache patients. JMPT, 2009;32(7):586-91.
14. Roy RA, Boucher JP, Comtois AS. Inflammatory response following a short-term course of chiropractic treatment in subjects with and without chronic low back pain.Journal of Chiropractic Medicine, 2010;9:107-114.
15. Teodorczyk-Injeyan JA, Injeyan HS, McGregor M, et al. Enhancement of in vitro interleukin-2 production in normal subjects following a single spinal manipulative treatment. Chiropr Osteopat, 2008;16:5.
16. Teodorczyk-Injeyan JA, et al. Interleukin-2 regulated in vitro antibody production following a single spinal manipulative treatment in normal subjects.Chiropr Osteopat, 2010;18:26.

Sensory Integration for Sensational Kids

A New Frontier for Caring for the Child With ADHD and Sensory Integration Dysfunction

By Claudia Anrig, DC

For doctors of chiropractic who serve the challenged child segment, it is not uncommon to hear, "Doctor, can chiropractic help my child with ADHD?" In my personal practice, I have seen many children helped with these disorders, and I have spoken to colleagues worldwide who shared their personal success stories. However, in all honesty, these success stories do not necessarily mean we can produce repeatable "breakthrough" results.

Over the years, I have never seen any specific technique, system of chiropractic analysis, protocol of care or adjunctive therapy (e.g., exercise, nutrition) to treat such challenging disorders. Now, however, the wait finally may be over. Monika Buerger, DC, and Robert J. Melillo, DC, DABCN, each have established timely, instructional programs for those seeking to serve these challenged pediatric population groups.

Dr. Buerger has been in private family practice for 15 years, specializing in sensory integration disorders in children. In her experience, she has found that many children who are diagnosed with ADD/ADHD, dyslexia, and various other autism spectrum disorders and learning disorders have an underlying problem with sensory integration dysfunction (SID). She notes that many of these children are being prescribed unnecessary medications and/or are not receiving proper treatment.

Sensory integration is the ability to take in, process, organize and assimilate sensory information so that we feel comfortable and secure; we then can respond appropriately to given situations and demands. All forms of learning occur through this process. Children with sensory SID experience a "disconnect" between the brain and the body (PNS and CNS) and have difficulty processing sensory information. Two rarely known senses are vestibular and proprioceptive sensations, both of which commonly function improperly among children with the above disorders.

Several years ago, Dr. Buerger became interested in this area and began extensive research, attending various seminars and workshops. Most sensory integration work has been performed in the occupational therapy arena; however, knowing the great impact chiropractic plays on the occulomotor, vestibular and proprioceptive systems, not to mention the entire nervous system, she knew the chiropractic profession needed to be a vital component in the treatment of these children. The more she researched and began to work in this field, it seemed to her that the neurological basis for SID was written for the chiropractic profession. Armed with a DC degree and a bachelor's degree in exercise physiology from California State University, Fresno, she began developing a program in her office for children with ADD and ADHD. As the children's success became known in her community, this area of her practice grew and began to include a variety of children with learning disorders. She also began to develop programs for local elementary schools.

Dr. Buerger is on the postgraduate faculty of several chiropractic college and is an instructor with the ICPA. She is also a contributing author to Pediatric Chiropractic. She shares a mission to teach doctors vital information regarding the treatment of children. As part of this mission, she developed a sensory integration program for the doctor of chiropractic, integrating the neurological principles of SID and those of chiropractic. The program in now offered through the ICPA and teaches how to perform a specific and detailed history, including what she calls a sensory and academic profile (SAP), a detailed neurological and sensory analysis and evaluation, specific short-lever adjustment protocols, home, school, and recreational recommendations, nutritional and biochemical considerations, and specific sensory exercise programs that are "graduated" in difficulty as children progress.

The program also discusses ways to implement a sensory integration program into your practice at any level, depending on how much space you have in your office, how much time you want to spend with patients, and how much you want to invest financially. The program is designed to give the doctor of chiropractic a firm understanding of the fundamental principles of neurosensory disorders and how they relate to children with ADD, ADHD, dyslexia, autism spectrum disorders, and various other learning and behavioral disorders. Its neurological basis gives the doctor of chiropractic a solid understanding as to why these children need chiropractic and its value as part of a drug-free treatment approach.

At the University of Bridgeport College of Chiropractic, Dr. Robert J. Melillo has been working with children in the area of neurobehavioral disorders like ADHD, dyslexia, learning disabilities, and autism for more than 10 years. He started to research the problem in 1995; at that time, the statistics showed a 250 percent increase in the use of Ritalin between 1990 and 1995. With these disturbing facts in mind, Dr. Melillo chose to devote much of his professional career toward trying to understand not only what causes ADHD and other neurobehavioral disorders, but also what can be done to correct these problems on a long-term basis, without the use of medication.

In 2004, Dr. Melillo published a textbook titled Neurobehavioral Disorders of Childhood - An Evolutionary Perspective, which describes what he believes to be the primary neurophysiologic mechanism that produces many of the most common neurobehavioral disorders. Applying this neurophysiologic mechanism to chiropractic, he focuses on three main areas: sensory/motor systems, biomechanical/nutritional, and neuropsychological, with the main concept revolving around hemispheric balance. His belief is that most of the symptoms seen in children with ADHD can best be explained by decreased activity in one hemisphere in the brain, often caused by an imbalance in the way that postural, vestibular and occulomotor information is being sent to the brain. As a result, one hemisphere is underactive, preventing the proper synchronization of the two hemispheres, which is necessary to properly share and process information.

From a chiropractic standpoint, an imbalance in postural muscle tone producing an observable subluxation complex may result in more gross postural disturbances, such as head tilts, which also could have central neurological consequences affecting and involving cognitive and behavioral functions.

Dr. Melillo recognizes that each child is different and should therefore be treated specifically; however, he has made his courses and treatment approaches more protocol-driven throughout the years for teaching purposes. He has developed specific protocols that involve not only precise adjustments, but also particular nutritional-, sensory-, motor- and cognitive-based protocols as well. The key, as he sees it, is to get the doctors to start seeing results, and protocols are the best means to that end.

A graduate education in neurology is not necessary for chiropractors wishing to take either of these new programs. The courses provide the chiropractor with all of the information necessary to treat children with ADHD and to help them feel comfortable interacting with other professionals such as teachers, occupational therapists, psychologists, and optometrists who also treat these children. To learn more about these programs, contact Monika Buerger, DC, at www.icpa4kids.com or Robert Melillo, DC, DABCN, atwww.carrickinstitute.org.