Immune Responses to Spinal Manipulation
SOURCE: Dynamic Chiropractic ~ May 6, 2011
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 the scientific literature, there have been occasional case reports that corroborate such findings, but no sound evidence to really document their veracity. These clinical observations remain suspended in that grey area unsubstantiated by scientific data to confirm their validity. Significant limitations of changes attributed to spinal manipulation in individual patients include
2) there is no blinding;
3) the improvement may simply be due to time;
4) they may be a nonspecific effect of care and attention;
5) it may be a regression to the mean; or
6) the result may be due to something other than spinal manipulation.
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.
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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 studies [8] on the pathophysiology of discogenic low back pain, sciatica, and ligamentous tissue damage-related pain [9] 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
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As usual, Malik has written an interesting and informative article but how does one extrapolate this data to the clinical situation? What is its clinical import or external validity?
Malik’s article gives me an opportunity to talk about a confusion or misunderstanding I believe occurs in some of the chiropractic literature on things like somatovisceral and viscerosomatic reflexes, stress and relaxation responses, and how they related to somatic based treatment of true visceral disorders.
The main misunderstanding that appears in chiropractic is with one particular interpretation of the clinical import of somatovisceral reflex phenomena that really has no good justification as far as I can see. Let me explain by first starting with a bit of history.
In 1995, Dr. Dale Nansel and I published a paper on somatovisceral responses that simulated visceral disease signs and symptoms which were then misdiagnosed but treated successfully with a musculoskeletal therapy. This introduced the concept of pseudo-visceral disease and referred pain phenomena. We should have followed up on that paper since more needed to be said about somatovisceral responses but we didn’t. Here I’ll fill in some of the extras that I think needed to also be talked about.
Our paper looked at ideas promoted mostly within chiropractic that claimed with damage to tissues of the spine, not only would regionally or segmentally related visceral organ reflex phenomena occur but these would eventually cause true regionally or segmentally related visceral disease in previously healthy organs. This does not mean some global chronic pain & stress related effects but specific neurological segmental disease producing relationship between spinal somatic tissues and organs.
To this day I haven’t found convincing evidence of such disease causing effects occurring and don’t see anyone else outside chiropractic claim such things including those in the Osteopathic profession.
Let’s start off in my assessment of whether there is something more to this by first taking a look at reflex sympathetic dystrophy (chronic regional pain syndromes) of the spine and then proceeding to reflexes responses and the ANS.
RSD is commonly due to relatively trivial trauma and happens with spinal injuries. But pain clinics that specialize in these cases never report the types of organ failures that one would expect are associated with somatovisceral responses which would cause regionally or segmentally related visceral disease. The ANS effects seen are restricted to mostly somatic structures (e.g. sweat glands), blood flow to the extremities (Raynauds phenomena), and bone density and vascular changes in the skin from disuse. The rest are more global chronic pain and stress related effects. RSD has stages or phases that reflect this progression. So this really gives one pause as to whether any injured somatic tissues of the spine could cause organ failure in segmentally related ways as is talked about within some sectors of the profession.
A few relationships exist but they are really nerve entrapment’s that cause say bladder paresis and dysfunction which in turn lead to fluid stasis and infection. Classic orthopedics and neurology and quite limited in scope.
Besides simulated disease misdiagnosis or globally related stress responses to chronic pain, what else could be going on with SMT, acupuncture or soft-tissue-work directed at para-vertebral structures if even RSD spine injury related patients don’t seem to get segmentally related reflex based visceral disease?
If one looks at the Osteopathic literature over at least the last two or three decades, one sees that viscerosomatic and somatovisceral reflexes are almost always related in a ways where the organic disease occurs first, this then sets up secondary reflex responses, some of which are viscerosomatic and paravertebral in nature. [BTW, there are phylogenetic and anatomic reasons for seeing paravertebral responses more often than extremity regions of the body.]
This means that pain or tenderness from things like secondary muscle spasms and joint dysfunctions are related through neurological segmental relationships to paravertebral structures but as SECONDARY responses. It’s plausible that these then could EXACERBATE to some degree the regionally related organ disease as the body tries to heal itself. However, there is no implication that they caused the disease in the first place.
Again, regionally or segmentally related somatovisceral reflexes are never talked about as being primary causes of healthy organ demise even in the Osteopathic literature. They are always seen as secondary phenomena. This makes sense with what is know about the CNS and is in line with what Malik has written
The clinical implications are that true organic disease sets up regionally related somatic dysfunctions and somatovisceral reflexes and that’s where the regional relationships come from.
One can then associate regions of the spine with organs through an understanding of neuroanatomy and the neurophysiology of pain.
Also, with these pain syndromes there is a development of tender points (possibly nodules) along the spine and chest which relates to dysfunctions in related organ systems.
The ones around the chest are referred to as Chapman’s reflexes in Osteopathy and are used to indicate a possible problem to an organ. A very recent master’s thesis looked a Chapman’s points and correlated them to acupuncture points and meridians with a very high degree of overlap (about 95%). I guess people who do muscle testing prefer that approach to implicate a system over tender point locations since regional muscular imbalances also occur as part of the pain response.
The heart can be used as an illustrative example of these secondary phenomena. Pain originating from heart disease can cause reflex muscle imbalances (spasms/weakening) and referred pain in the neck, back and arm. The reason for this pattern is because of convergence of visceral afferent’s from the vagus and thoracic segments with common pools of neurons in the brain stem and spinal cord. These set up the para-vertebral responses that clinicians see and that DO’s like Dr. Beal wrote about in the Osteopathic literature. Addressing these could then have an effect in adjusting or reestablishing homeostasis or a better healing environment for the organic problem. But the question then is “by how much?”
SMT trials in Osteopathy have shown that to some extent when treating organic disease. Recently several larger well designed trails have confirmed that SMT to the back along with standard medical care to the organic problem does better when compared to medical care alone by either slightly speeding up healing time or if not speeding things up, have reduced the amount of medical treatment (e.g. drugs) required for proper care.
More research needs to be done to optimizing this effect.
The body goes through constant fluctuations of “vagotonia” and “sympathicotonia” throughout the day. When an organ goes through it’s disease, healing and resolution phases with a disorder, there maybe optimal times when it’s environment can be affected in a positive way by either decreasing or increasing the effects of the ANS to help facilitate the bodies self-healing response. So, it may not be as simple as just removing the secondary somatic dysfunction to the spine. In fact it maybe that in chronic disease states one wants cause a temporary dysfunction or benign trauma to activate or stimulate a self-healing response that has just stopped responding to the disorder. There are other possibilities as well.
This leads then to some thoughts (not original in any way) on what SMT or say acupuncture/dry needling maybe doing to areas that don’t really have any significant somatic dysfunctions, chiropractic subluxations, or whatever.
In certain situations, these therapies may act like benign or virtuous traumas which “trick” or “fool” the bodies self-healing mechanisms to activate in regionally related ways. They could be thought of as “inoculations.”
So these treatments don’t necessarily always remove some “interference” due to dysfunction in the local tissues that they are directed at. Instead they indirectly do something else somewhere else. Again, further research could relate these “inoculations” to phases of disease for an optimal result as mentioned before … if that’s what’s really going on in some cases.
However, this also brings up another problem in interpreting what’s really happening in clinical practice in addition to the things I’ve already mentioned like somatic mimicry, global stress/relaxation responses, secondary exacerbating reflexes associated with visceral disease. The additional problem is that there may never have been an exacerbating somatic dysfunction at all in _some_ of these cases except for the actual therapy itself acting as a benign or virtuous trauma. Implications one needs to think about.
Besides the standard issues Malik mentions of natural history and so on, I believe there are many other interesting ways that erroneous clinical interpretations can occur when looking at somatovisceral relations and even the existence of somatic lesions as I just have outlined.
Finally, I’m open to the possibility of a true somatovisceral regionally or segmentally related problem actually causing disease in previously healthy organ. However, no one so far has provided convincing evidence that this occurs in the great extent some think it occurs but one never knows what the future will bring.
Mark Szlazak, D.C.
RESPONSE from Frank:
I’m with you 100%, and LOVE that article. It’s the featured article above our Conditions That Respond Well to Chiropractic Page
The clinical truth is…whether it’s a pseudo-visceral complaint or not, their MD most likely had them on the drugs that *treat* that disease state, and when chiropractic helped resolve the complaint, the only mistake the DC made was in WHAT they (or their MD) called the *disorder* the patient presented with.
I have seen this in children who were diagnosed with Asthma, who were able to discontinue steroid inhalants after getting adjusted. The truth…they didn’t have asthma…they had nerve interference/subluxation/manipulable lesion…call it what you will…and that was the *cause* of their pseudo-asthma, and Chiropractic is what helped resolve it.
THANK YOU SO MUCH for writing that article with Dr. Nansel !!!
Thanks and no problem.
However the response that I posted talks about another issue and it has to do with exacerbating factors as opposed to primary causes. I’m not talking about simulated visceral disease in this post. I hope I made that clear even though there are typos I didn’t catch until after posting. I wish there was some edit buttons, I type slowly with one finger and think faster than my hands can move.
Mark Szlazak, D.C.
RESPONSE from Frank:
The updated comment is now in place Mark.
Mark,
I often re-write my own commentary after I’ve had time to rethink. Just send it when ready.
You are also welcome to write a feature article for our Blog. It would certainly garner more attention than a comment tacked onto the bottom of a post.
It would also give you a chance to format it, add colors as highlights, pictures, or whatever. If you send it as a Word document, I’ll see that it gets posted formatted correctly.
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