Chiropractic Journal of Australia 2016 (Jan); 44 (1): 1–8 ~ FULL TEXT
Joe Evans, PhD
CEO, Sense Technology Inc.
1052 Corporate Lane,
The purpose of this study was to examine the possible origins of non-specific or atraumatic back pain by applying the Gate Theory of pain and current physiologic concepts. I present a theory that accounts for the initiation and potential consequences of neuromusculoskeletal pain incorporating failure of the mechanism of muscle relaxation and resulting in pain and compromise of the lymphatic system. The theory provides an alternative to current theories and hypotheses of the cause and consequences of neuromusculoskeletal pain.
Keywords: Pain; Muscular System; Muscle Relaxation
From the FULL TEXT Article:
The incidence of low back and other neuromusculoskeletal pain continues to
increase, with low back pain being the leading cause of disability in the world. [1, 2] In addition to the loss of quality of life for those experiencing musculoskeletal
pain, the cost to both patients and society is significant and increasing:
The annual cost of chronic pain in the United States, including
healthcare expenses (direct medical costs), lost income, and lost
productivity, is estimated to be $635 billion. This is significantly higher
than the estimated annual costs in 2010, dollars of heart disease ($309
billion), cancer ($243 billion), and diabetes ($188 billion).
Total estimated medical costs associated with back and neck pain, two
of the commonest presentations of patients with chronic pain,
increased by 65% between 1997 and 2005, to about $86 billion a year.
Overall, pharmaceutical expenditures related to back and neck pain
increased by 188% between 1997 and 2005, but costs associated with
prescription narcotics rose by an astounding 423%.
In the US, the estimated annual direct medical cost of low back pain is
$30 billion. In addition, the impact of back pain is $100-200 billion in
decreased wages and lost productivity while in Australia, the direct cost
of is estimated to be AU dollars 1.02 billion in 2001. And the indirect
costs of AU dollars 8.15 billion giving a total cost of AU dollars 9.17
Patients with chronic pain have more hospital admissions, longer
hospital stays, and unnecessary trips to the emergency department. 
Musculoskeletal pain resulting from trauma such as whiplash, repetitive strain
injury and heavy lifting is relatively easy to understand; however, the cause and,
therefore, best treatment for acute or chronic nonspecific musculoskeletal
complaints i.e., those complaints that have no known underlying pathology, is
elusive. For example, it has been estimated that 90% of low back pain is
classified as non-specific.  Recasting neuromusculoskeletal dysfunction in
light of current pain theory has resulted in the identification of a possible underlying cause or initiating event of non-specific or atraumatic musculoskeletal pain.
Serious study of the phenomena of pain did not begin until the 1960s. In 1965,
Melzack and Wall published the Gate Theory of Pain.  The Gate Theory of
pain has undergone thorough and extensive testing at all levels and currently
represents the generally accepted view of the perception of pain.  Recent
research has identified specific interneurons in the dorsal horn of the spinal cord
that perform the function of the “gate”.  The Gate Theory serves here as a
framework for development of insights into the underlying phenomena of nonspecific
musculoskeletal dysfunction and its accompanying pain.
Within this framework, it is key to recognize that the perception of pain is not
always due to an increase in nociception. Reduced proprioceptive input to the
CNS will also result in pain by creating an apparent increase in nociceptive
input and this was recently demonstrated experimentally through selective
disabling of the specific interneurons of the gate.  A mechanism of muscle
dysfunction that results in a reduction of proprioception thereby altering the
balance between nociception and proprioception, would provide an explanation
of atraumatic pain.
Understanding muscle dysfunction is predicated on an understanding of normal
muscle function. In normal muscle, contraction of individual muscle fibers is
initiated through the action of large myelinated nerve fibers which innervate
several to hundreds of fibers. Each nerve branch terminates close to the middle
of the individual muscle fiber with multiple branches which form the motor end
plate. Excitation of these nerve fibers results in the release of acetylcholine
which, in turn, open acetylcholine gated channels in the muscle membrane. The
opening of these channels allows sodium and calcium ions to rapidly pass to
the inside of the muscle membrane and depolarize the membrane, resulting in
muscle contraction through the generation of an action potential which travels in
both directions from the center of the muscle fiber toward each end. 
Depolarization of the surface membrane of the muscle fiber as described above
is accompanied by the release of calcium ions from the sarcoplasmic reticulum
which cause contraction of the myofibrils resulting in contraction of the muscle
fiber itself. Relaxation of the muscle fiber is enabled by the adenosine
triphosphate (ATP) energized calcium pump, which returns calcium ions to the
sarcoplasmic reticulum where they are available for the initiation of the next
muscle contraction.  If the calcium pump malfunctions, the muscle cannot
relax. A failure of the calcium pump would account for the inability of a muscle fiber to relax, reducing proprioceptive input to the CNS from the sensory organs
of the muscle fiber or fibers involved independently of motor nerve input.
Statement of the Neurochemical Theory of Musculoskeletal Dysfunction
The theory of neuromusculoskeletal dysfunction presented here is comprised
An acute stage consisting of an initiating event wherein a portion of
muscle mass in a normal contractile state is prevented from extending
or relaxing due to a local failure of the calcium pump. The inability of
the muscle to relax results in the reduction of proprioceptive input to
the CNS and the perception of pain.
If the muscle dysfunction is not immediately corrected, the initial
muscle dysfunction will result in compromise of the lymphatic system
resulting in potentially serious and poorly understood consequences for
the health of the individual.
Such consequences may include but are not limited to:
decreased blood flow,
production of abnormal products of cellular metabolism
and other potentially serious health effects. (Figure 1)
Diagram of neurochemical hypothesis of atraumatic neuromusculoskeletal pain
The theory of neuromusculoskeletal pain presented here incorporates features
rendering the theory unique compared to other attempts to explain non-specific
musculoskeletal pain. Among these features are:
A failure of the ATP powered calcium pump, which is fundamental to
muscle relaxation, is proposed as the initiating event of atraumatic
That cessation of proprioception from constricted muscle mass to the CNS
is the cause of acute musculoskeletal pain rather than the view that
intense proprioception is the cause of pain;
That muscle dysfunction in the form of persistent contraction leads to
compromise of the lymphatic system.
The theory proposed here combines known processes and functions to create a
basic building block that may arguably be combined with other components of
skeletal function to represent the allopathic trigger point, the osteopathic lesion,
the chiropractic subluxation the physical therapy movement restriction and the
cardiologist’s myocardial infarction. [10-13]
The fact that the function of the calcium ion pump in muscle relaxation is not
cited elsewhere in the literature as a possible cause of muscle constriction and
consequent pain may be explained by the focus on increased nociception
through injury or trauma as the primary cause of muscle pain and the relative
neglect of the role of calcium in membrane depolarization coupled with the
emphasis on the concept of “facilitation” proposed by Korr. 
The seminal work of Huxley and Stampfli  which identified the sodium-potassium
pump and the role of these ions in nerve membrane depolarization
was based on the study of axons of squid and giant mollusks which is not totally
applicable to vertebrates. In his review of the history of the discovery of the role
of the calcium ion in vertebrates, Tsien  attributes the dominance of the
sodium-potassium paradigm as the main factor inhibiting the field of ion channel
exploration for over forty years. The fundamental role of calcium in the nervous
system has only recently been appreciated. In fact, a Nobel Prize was awarded
for the discovery of the role of calcium ion channels in synaptic communication
as recently as 2013.
Recent work utilizing x-ray diffraction has clarified details of the structure and
function of the calcium pump Toyoshima. [17, 18] These studies have revealed
that not only ATP and calcium but also magnesium, phosphorous, sarcolipin, as
well as the maintenance of pH are necessary for the function of the pump.
Toyoshima  in fact, expressed surprise that the failure of the calcium pump
has not been recognized as being related to more disease states:
“Because Ca2+ is so fundamental in the regulation of biological processes, malfunction of Ca2+ pumps is likely to be deleterious to living organisms.”
A major consequence of the theory presented here is that muscular dysfunction
results in a compromise of the lymphatic system. Once the muscle or portion of
muscle becomes unable to relax, the lack of movement within the structure of
the muscle reduces the drainage of lymph from the cells of the muscle. If the
lymphatic system is severely compromised, the cellular metabolism of the
affected muscle volume will be altered. While not as dramatic as failure of the
cardiovascular or respiratory systems, failure of the lymphatic system can result
in serious consequences, even death within 24 hours.  Maintenance of the
health of the lymphatic system through prevention of compromise of that system
by muscle constriction may be the most powerful argument for regular visits to
providers skilled in manual therapy.
As predicted by Travell , failure of the muscle to relax should result in a
reduction of the blood flow through that portion of the muscle. Such an effect
has been measured in the case of active myofacial trigger points (aMTPs)
where abnormal blood velocity measures were found to distinguish between
active and latent myofacial trigger points. [20-22] The resulting ischemia is likely
to result in the generation of recently discovered and as yet poorly understood
inflammatory agents which trigger the innate immune system producing
increased nociception and therefore increased pain. Since this immune
reaction is not associated with invasion of the body by pathogens, this type of
inflammatory response is referred to as “sterile” inflammatory response and is
associated with mechanical trauma, ischemia, stress and environmental factors.  The inflammatory agents expressed which trigger the sterile inflammatory
response are known as danger associated molecular patterns (DAMPS) 
and include substances such as cytokines, IL-1β and IL-18, along with the
DAMP High Mobility Group Box 1 (HMGB1).
With regard to the theory
described here, the sterile inflammatory response would appear to be a
secondary result of the initial failure of muscle relaxation. Therefore, an
expected result of manual therapy that succeeds in reversing the initial muscle
dysfunction would also be expected to reduce the levels of DAMPS in the
circulation. Evidence in support of this proposition is found in the work of
Teodorczyk-Ineyan et.al.  who concluded that spinal manipulative therapy
was associated with down regulation of inflammatory responses “via a central
yet unknown mechanism.”
By starting with the Gate Theory of Pain and applying current knowledge of
basic physiology to the problem of back pain, we have arrived at a potentially
useful new hypothesis regarding the likely cause of atraumatic back pain.
Rather than concluding that all back pain is the result of tissue injury caused by
overuse, buckling, trauma, or an aberrant neurological feedback that maintains
muscles in a continuous state of contraction, a failure of the mechanism that
permits muscle relaxation to occur is proposed. Not being able to exit the
contracted state, the normal proprioceptive feedback associated with the
involved muscle will be absent resulting in an excess of nociceptive input to the
Gate resulting in the perception of pain. Compromise of the lymphatic system
due to lack of normal muscle function may follow. This hypothesis is supported by existing experimental evidence and appears to have broad implications for
diagnosis and treatment of conditions extending far beyond the immediate
problem of back pain.
The theory presented here provides an alternative to current theories and
hypotheses of the cause and consequences of musculoskeletal pain. The
theory provides useful insights for the improvement of therapeutic modalities not
only for relief but also prevention of pain and maintenance of a healthy
neuromusculoskeletal system. The key features of the theory are the initiation
of pain through the inability of muscles in a state of contraction to relax due to a
failure of the ATP-calcium pump and the compromise of the lymphatic system
through the reduction of lymph flow.
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