The June 2015 issue of the journal Scientific American has an article by primary care physician Wajahat Z. Mehal, MD, from the Department of Veterans Affairs Medical Center in Connecticut, and Yale University, titled (1):
Cells on Fire
In this article, Dr. Mehal notes that inflammation is set in motion by cells of the immune system, and that it is helpful because it kills pathogens and blocks their spread in the body. The inflammatory cascade, initiated by the innate immune response’s macrophages, weakens and immobilizes adverse microbes.
However, the same inflammatory cascade can occur when no microbes exist, triggered as a consequence of tissue damage and/or excessive tissue stress. This inflammatory response can, in-and-of-itself, become chronic and cause additional tissue damage. In other words, as much as acute inflammation can be beneficial (containing and/or killing pathogens), chronic inflammation can be deleterious, serving no useful purpose.
Consequently, Dr. Mehal broadly categorized the inflammatory response into two categories:
1) Infectious inflammation:
This is an inflammatory response that is designed to contain and/or kill pathogens.
This response is critical for individual and species survival.
2) Sterile inflammation:
This is an inflammatory response in which there are no associated pathogens, a response that is triggered by tissue injury and /or excessive tissue stress.
This response often becomes chronic. As such, this response is excessive and harmful.
Pathology History
A decades synopsis of global leading experts, expressed in leading reference texts printed by top medical publishers
In 1952, William Boyd, MD, Professor Emeritus of Pathology at the University of Toronto, published his reference text, titled (2):
PATHOLOGY
Structure and Function in Disease
In this text, Dr. Boyd states:
“The inflammatory reaction tends to prevent the dissemination of infection. Speaking generally, the more intense the reaction, the more likely the infection to be localized.”
In 1970, the eighth edition of Dr. Boyd’s PATHOLOGY text is published
(3): In chapter 4, titled “Inflammation and Repair,” Dr. Boyd states:
“Inflammation is the most common, the most carefully studied, and the most important of the changes that the body undergoes as the result of disease.”
Dr. Boyd notes that in chronic inflammation, the “only cells that proliferate are the fibroblasts.” Consequently, the chronic inflammatory response is considered to be a “fibroblast reaction,” or “fibrosis.” The lesion of chronic inflammation becomes more and more fibrous as the collagen is laid down. The resulting fibrosis is much more marked than in acute inflammation situations. Also, the “newly-formed fibrous tissue invariably contracts as it becomes older.”
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In 1976, physicians WAD Anderson, MD, and Thomas Scotti, MD, published the ninth edition of their book titled (4):
Synopsis of Pathology
Drs. Anderson and Scotti were Professors of Pathology at the University of Miami School of Medicine. Similar to Boyd, they title chapter 3 of their text “Inflammation and Repair,” in which they state:
“Inflammation is the most common and fundamental pathological reaction.”
The agents leading to inflammation include “microbial, immunologic, physical, chemical, or traumatic.”
“Chronic inflammation is a process that is prolonged, and proliferation (especially in connective tissues) forms a prominent feature.”
“The proliferative activity, leading to the production of abundant scar tissue, may in itself be distinctly harmful.”
“The final healed state is achieved by development of a connective tissue scar.”
An important premise from Drs. Anderson and Scotti is that in chronic inflammation, “abundant” scar tissue may form, and this connective tissue scar may “itself be distinctly harmful.”
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In 1979, Harvard Medical School professors Stanley Robbins, MD, and Ramzi Cotran, MD, published the second edition of their book, titled (5):
PATHOLOGIC BASIS OF DISEASE
Similar to Boyd, Anderson and Scotti, Robbins and Cotran, title chapter 3 of their text “Inflammation and Repair.” Robbins and Cotran state:
“Inflammation serves to destroy, dilute, or wall-off the injurious agent.”
“Without inflammation, bacterial infections would go unchecked.”
But, “inflammation itself may be potentially harmful:”
Chronic inflammation is “generally of longer duration and is associated histologically with the presence of lymphocytes and macrophages and the proliferation of small blood vessels and fibroblasts.”
Tissues are replaced by “filling the defect with less specialized fibroblastic scar-forming tissue.”
“Reparative efforts may lead to disfiguring scars, fibrous bonds that limit the mobility of joints, or masses of scar tissue that hamper the function of organs.”
It is of particular interest to chiropractors that this cascade of inflammation and fibrosis may “limit the mobility of joints.”
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In 1982, orthopedic surgeon Sir James Cyriax, MD, published the eighth edition of his book titled (6):
Textbook of Orthopaedic Medicine:
Diagnosis of Soft Tissue Lesions
In this text, Dr. Cyriax notes that harmful infections create tissue destruction, resulting in inflammation. Our body recognizes this inflammation and attempts to “wall off” the infectious pathogens by creating a fibrous response. Cyriax states:
“The excessive reaction of tissues to an injury is conditioned by the overriding needs of a process designed to limit bacterial invasion. If there is to be only one pattern of response, it must be suited to the graver of the two possible traumas. However, elaborate preparation for preventing the spread of bacteria is not only pointless after an aseptic injury, but is so excessive as to prove harmful in itself. The principle on which the treatment of post-traumatic inflammation is based is that the reaction of the body to an injury unaccompanied by infection is always too great.”
Once again, a link is expressed between infection, inflammation, and excessive-harmful tissue fibrosis.
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In 1983, physicians Steven Roy and Richard Irvin published their book on sports injury titled (7):
Sports Medicine:
Prevention, Evaluation, Management, and Rehabilitation
In this book, Roy and Irvin state:
“It is important to realize that the body’s initial reaction to an injury is similar to its reaction to an infection. The reaction is termed inflammation and may manifest macroscopically (such as after an acute injury) or at a microscopic level, with the latter occurring particularly in chronic overuse conditions.”
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In 1986, physician and physiologist, Arthur Guyton, MD, published the seventh edition of his book, titled (8):
Textbook of Medical Physiology
At the time of publication, Dr. Guyton was Chairman and Professor of Physiology and Biophysics at the University of Mississippi School of Medicine. Dr. Guyton states:
“One of the first results of inflammation is to ‘wall off’ the area of injury from the remaining tissues.”
“This walling-off process delays the spread of bacteria or toxic products.”
Once again, Guyton expresses the concept of a sequential link between infection, inflammation, and fibrosis. This fibrosis, in the absence of inflammation, creates excessive mechanical impairments that are both mechanically and neurologically deleterious to the individual.
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In 1992, physician I. Kelman Cohen and associates published their book titled Wound Healing, Biochemical & Clinical Aspects (9), in which they state:
“There are two important consequences of being a warm-blooded animal. One is that body fluids make optimal culture media for bacteria. It is to the animal’s advantage, therefore, to heal wounds with alacrity in order to reduce chances of infection.”
“The prompt development of granulation tissue forecasts the repair of the interrupted dermal tissue to produce a scar.” In addition to providing tensile strength, scars are believed to be a barrier to infectious migration.
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For more than half a century, experts in pathology, physiology, orthopedics, sports injuries, and wound healing have suggested the following model:
Inflammation is a paradox. Inflammation can directly kill pathogens. Inflammation also triggers a fibrous response that walls-off infection so that the pathogens are less likely to spread and kill the host. Without inflammation we would die of infection. All who are alive today had ancestors that could successfully initiate an inflammatory response, kill pathogens, and wall off the pathogens.
Infection can kill the young before they can reproduce. Hence, a strong inflammatory response is genetically selected, giving those with such a response a survivability advantage. Our ancestors genetically handed down these traits and we possess them. In a world prior to the availability of antibiotics, inflammation, with reactive walling-off fibrosis to contain pathogens, is desirable because it increases host survivability.
Infections were the primary cause of death for humans for millennias. Infections remained the primary cause of human death until very recent history, only a few decades ago.
Infection is not the only cause of inflammation. As noted above, inflammation is also triggered by trauma, excessive tissue stress, chemicals, and immunologic responses. Apparently, the body cannot distinguish the different causes of inflammation from each other, and they all trigger a fibrous response. “The resolution of inflammation in the body is fibrosis.”
This fibrosis response is necesasary when there is an infection, it is life-saving. However in an aseptic sterile injury or tissue stress, the fibrous response is excessive and it creates adverse mechanical deficits. These adverse mechanical deficits create tissue stiffness and limit the mobility of joints. These mechanical deficits impair local biomechanical function, affecting performance, generating pain, and accelerating degenerative changes.
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SOLUTIONS
The management of adverse tissue fibrosis creates the pathoanatomical basis for mechanical based health care disciplines, including chiropractic. Abnormal tissue fibrosis can be minimized with early, persistent, controlled motion. Once established, abnormal tissue fibrosis can be improved with the use of a variety of motion applications. Support for the value in using motion to treat soft-tissue injuries has been in the literature for decades. As an example, Beverly Hills neurosurgeon Emil Seletz, associated with the medical school at the University of California, Los Angeles (UCLA), noted in the Journal of the American Medical Association in 1958, the following, with respects to the management of whiplash soft-tissue injuries (10):
“During injury, hemorrhage within the capsular ligaments gives rise to swelling of the nerves and eventually adhesions between the dural sleeve and the nerve root; these factors give rise to symptoms that may be prolonged for months or even years after the injury.”
“In reviewing the types of treatment with a number of specialists in this field, it is found that, while therapy naturally varies to suit the individual need, it consists primarily of local heat in the form of hot wet packs and cervical traction, followed by very gentle massage and manual rotations.”
“The importance of a carefully planned scheme of treatment must be emphasized to the patient, and treatments must be religiously carried out daily during the first two or three weeks (and then about three times weekly), depending, of course, on the individual case.”
“Delay or faulty treatment leads to adhesions about the facets and scarring about the capsular ligaments, persistent spasm, congestive lymph edema, and fibrosis of muscles, swelling, and eventual adhesions of nerves within the nerve root canals.”
“The resultant faulty posture in neglected cases enhances the degeneration of the intervertebral disks, as well as spur formation in the lateral co-vertebral articulations, which on the roentgenogram has come to be known as traumatic arthritis.”
“I cannot too strongly emphasize the urgency of early and persistent therapy, always by a specialist in this field.”
“Occasionally, a patient is seen with persistent complaints of head, neck, and shoulder pain, who has had on surgical exposure persistent swelling and adhesions of several nerve roots within the dural sleeve of exit. It is most likely that early, persistent, and adequate therapy by those expertly trained in physical medicine will prevent most patients from developing a surgical condition.”
On this topic, Cyriax’s comments include a review of the 1940 primary research by ML Stearns (11), stating:
“Her (Stearns) main conclusion on the mechanics of the formation of scar tissue was that external mechanical factors, were responsible for the development of the fibrillary network into orderly layers. Within four hours of applying a stimulus, an extensive network of fibrils was already visible around the fibroblasts; during the course of 48 hours this became dense enough to hide the cells almost completely: and in 12 days a heavy layer of fibrils had appeared. At first the fibrils developed at random, but later they acquired a definite arrangement, apparently as a direct result of the mechanical factors. Of these factors, movement is obviously the most important and equally obvious it is most effective and least likely to cause pain before the fibrils have developed an abnormal firm attachment to neighboring structures. When free mobility was encouraged from the onset, the fibers in the scar were arranged lengthwise as in a normal ligament. Gentle passive movements do not detach fibrils from their proper formation at the healing breach but prevent their continued adherence at normal sites. The fact that the fibrils rapidly spread in all directions provides sufficient reason for beginning movements at the earliest possible moment; otherwise they develop into strong fibrous scars (adhesions) that so often cause prolonged disability after a sprain.”
Additionally, Cyriax notes:
“When pain is due to bacterial inflammation, Hilton’s advocacy of rest remains unchallenged and is today one of the main principles of medical treatment. When, however somatic pain is caused by inflammation due to trauma, his ideas require modification. When non-bacterial inflammation attacks the soft tissues that move, treatment by rest has been found to result in chronic disability, later, although the symptoms may temporarily diminish. Hence, during the present century, treatment by rest has given way to therapeutic movement in many soft tissue lesions. Movement may be applied in various ways: the three main categories are:
(a) Active and resistive exercises:
(b) Passive, especially forced movement: and
(c) Deep massage.”
“Tension within the granulation tissue lines the cells up along the direction of stress. Hence, during the healing of mobile tissues, excessive immobilization is harmful. It prevents the formation of a scar strong in the important direction by avoiding the strains leading to due orientation of fibrous tissue and also allows the scar to become unduly adherent, e.g. to bone.”
In 1983, sports physicians Steven Roy and Richard Irvin note (7):
“The injured tissues next undergo remodeling, which can take up to one year to complete in the case of major tissue disruption. The remodeling stage blends with the later part of the regeneration stage, which means that motion of the injured tissues will influence their structure when they are healed. This is one reason why it is necessary to consider using controlled motion during the recovery stage. If a limb is completely immobilized during the recovery process, the tissues may emerge fully healed but poorly adapted functionally, with little chance for change, particularly if the immobilization has been prolonged. Another reason for encouraging controlled motion is that any adhesions that develop will be flexible and will thus allow the tissues to move easily on each other.”
In 1986, physician John Kellett notes (12):
Acute inflammation is beneficial when one has acute infection. However, the “acute inflammatory phase of the body’s response to trauma is apparently of no benefit.”
“The micropathology of acute soft tissue trauma has been investigated. Healing of ligaments and soft tissue injuries in general has been shown to occur by fibrous repair (scar tissue) and not by regeneration of the damaged tissue.”
“Early mobilization, guided by the pain response, promotes a more rapid return to full activity.”
“Early mobilization, guided by the pain response, promotes a more rapid return to full functional recovery.”
“The collagen is remodeled to increase the functional capabilities of the tendon or ligament to withstand the stresses imposed upon it.”
“It appears that the tensile strength of the collagen is quite specific to the forces imposed on it during the remodeling phase: i.e. the maximum strength will be in the direction of the forces imposed on the ligament.”
Dr. Cohen (9) and associates also comment on the value of range of motion exercises in the management of soft tissue injury, stating:
“During the phase of wound contraction, the active cellular process is locked into position by increasing amounts of rigid collagenous scar. Frequent, gentle exercise can be used to put an extremity joint through a full range of motion and keep the newly developing scar tissue stretched and remodeled. Frequent use of the range of motion exercises is important to keep the developing and contracting scar tissue from becoming a rigid, fixed scar contracture. Range of motion exercises concentrate on remodeling the newly laid collagen before it develops into a rigid scar contracture.”
In 1994, Halldor Jonsson and associates (13) performed surgical evaluations of 50 patients with chronic whiplash symptoms, showing a “high incidence of discoligamentous injuries in whiplash-type distortions.” The authors noted:
“The injured spinal segments had become increasingly stiffer over 5 years, which may reflect healing of unrecognized soft tissue injuries.”
“The most likely source of radicular symptoms is perineural scarring.
Therefore, patients with neck distortions after traffic accidents should be mobilized early within the limits of pain to prevent scar transformation of hidden injuries.”
In 2000, Pekka Kannus, MD, Ph.D., published a study in the journal The Physician and Sports Medicine (14). Dr. Kannus is chief physician and head of the Accident and Trauma Research Center and sports medicine specialist at the Tampere Research Center of Sports Medicine at the UKK Institute in Tampere, Finland. His article titled “Immobilization or Early Mobilization After an Acute Soft-Tissue Injury?” notes:
Prolonged inflammation may lead to excessive scarring. Therefore, early, effective treatment seeks to prevent prolonged inflammation and excessive scarring.
“Experimental and clinical studies demonstrate that early, controlled mobilization is superior to immobilization for primary treatment of acute musculoskeletal soft-tissue injuries and postoperative management.”
“The current literature on experimental acute soft-tissue injury speaks strongly for the use of early, controlled mobilization rather than immobilization for optimal heating.”
Experimentally induced ligament tears in animals heal much better with early, controlled mobilization than with immobilization.
“The superiority of early controlled mobilization has been especially clear in terms of quicker recovery and return to full activity without jeopardizing the subjective or objective long-term outcome.”
“Controlled experimental and clinical trials have yielded convincing evidence that early, controlled mobilization is superior to immobilization for musculoskeletal soft-tissue injuries. This holds true not only in primary treatment of acute injuries, but also in their postoperative management. The superiority of early controlled mobilization is especially apparent in terms of producing quicker recovery and return to full activity, without jeopardizing the long-term rehabilitative outcome. Therefore, the technique can be recommended as the method of choice for acute soft-tissue injury.”
Spinal manipulation is a form of passive controlled motion that mechanically influences more tissue than does either active or passive motions (15). Consequently, it is superior to other therapies in remodeling periarticular fibrosis and in reducing intra-articular adhesions. As noted by orthopedic surgeon Kirkaldy-Willis, MD:
In chronic cases [of back pain], there is a shortening of periarticular connective tissues and intra-articular adhesions may form; manipulations [adjustments] can stretch or break these adhesions.
“Spinal manipulation is essentially an assisted passive motion applied to the spinal apophyseal and sacroiliac joints.”
Conclusions
The discussion and references above support the concept that adverse pathogens cause tissue destruction and subsequent inflammation. The body evolved in a manner to wall-off the area of inflammation by over healing the region with a fibrous response. The fibrous response becomes a physical barrier, reducing the ability of the pathogens to spread to other regions of the body, thereby improving the host’s chances for survival.
However, when inflammation is caused by non-infectious mechanisms, the same fibrotic tissue response occurs. In such cases, without infectious pathogens, the fibrotic tissue response is excessive, resulting in mechanical harm to the host. This harmful tissue fibrosis is worsened with early immobilization of the affected tissues. This tissue fibrosis is minimized with early persistent controlled mobilization. Established harmful tissue fibrosis is best managed with specific controlled motion. Periarticular and intra-articular adhesions probably respond best to joint manipulation.
REFERENCES
- Mehal WZ; Cells on Fire; Scientific American; June 2015; Vol. 312; No. 6; pp. 45-49.
- Boyd W; PATHOLOGY: Structure and Function in Disease; Lea and Febiger, 1952.
- Boyd W; PATHOLOGY: Structure and Function in Disease; Eighth Edition; Lea & Febiger; Philadelphia; 1970.
- Anderson WAD, Scotti TM; Synopsis of Pathology; Ninth Edition; The CV Mosby Company; 1976.
- Robbins SL, Cotran RS; PATHOLOGIC BASIS OF DISEASE; Second Edition; WB Saunders Company; Philadelphia; 1979.
- Cyriax, James; Textbook of Orthopaedic Medicine, Diagnosis of Soft Tissue Lesions; Bailliere Tindall; Volume 1; eighth edition; 1982.
- Roy, Steven; Irvin, Richard; Sports Medicine: Prevention, Evaluation, Management, and Rehabilitation; Prentice-Hall; 1983.
- Guyton A; Textbook of Medical Physiology; Saunders; 1986.
- Cohen, I. Kelman; Diegelmann, Robert F; Lindbald, William J; Wound Healing, Biochemical & Clinical Aspects; WB Saunders; 1992.
- Seletz E; Whiplash Injuries, Neurophysiological Basis for Pain and Methods Used for Rehabilitation; Journal of the American Medical Association; November 29, 1958; pp. 1750–1755.
- Stearns ML; Studies on development of connective tissue in transparent chambers in rabbit’s ear; American Journal of Anatomy; Vol. 67 1940; p. 55.
- Kellett J; Acute soft tissue injuries--a review of the literature; Medicine and Science in Sports and Exercise; Oct. 1986;18(5):489-500.
- Jonsson H, Cesarini K, Sahlstedt B, Rauschning W; Findings and Outcome in Whiplash-Type Neck Distortions; Spine; Vol. 19; No. 24; December 15, 1994; pp. 2733-2743.
- Kannus P; Immobilization or Early Mobilization After an Acute Soft-Tissue Injury?; The Physician And Sports Medicine; March, 2000; Vol. 26; No. 3; pp. 55-63.
- Kirkaldy-Willis WH, Cassidy JD; Spinal Manipulation in the Treatment of Low back Pain; Canadian Family Physician; March 1985; Vol. 31; pp. 535-540.
