William Salvatore, D.C.

Why is Chronic Low Back Pain So Prevalent and Often so Treatment Resistant?

The Concept of Hyper-innervation, Neoneuralisation, Receptive Field Enlargement

Pain, like all perceptions, is a cortical event. Pain is experienced in the brain. Pain perception in the brain begins in a peripheral tissue and is transmitted to the brain via a nerve. Thus, the peripheral tissue source of pain must have a nerve supply (be innervated by sensory nociceptive nerves).

Eight decades of evidence (since 1934) argues that the primary peripheral tissue source for chronic low back pain is the intervertebral disc (1, 2, 3, 4, 5, 6, 7). Several lines of investigation support this evidence, including:

“Investigations have been performed in which thin nylon threads were surgically fastened to various structures in and around the nerve root. Three to four weeks after surgery these structures were irritated by pulling on the threads, but [lower back] pain resembling that which the patient had experienced previously could be registered only from the outer part of the annulus” of the disc.

[Nachemson in reference #4, describing the primary research of Smyth and Wright, reference #3).

In 1991, Dr. Stephen Kuslich and colleagues published a study titled (6):

The Tissue Origin of Low Back Pain and Sciatica:
A Report of Pain Response to Tissue Stimulation During 
Operations on the Lumbar Spine Using Local Anesthesia

The authors performed 700 lumbar spine operations using only local anesthesia to determine the tissue origin of low back and leg pain. They presented the results on 193 consecutive patients they studied prospectively. The authors concluded:

“Back pain could be produced by several lumbar tissues, but by far, the most common tissue of origin was the outer layer of the annulus fibrosis.”

As noted above, accepting that the intervertebral disc is the primary source of chronic low back pain, it would mandate that the intervertebral disc has a sensory nociceptive nerve supply. Although there are respected authors of the modern era continuing to claim the intervertebral disc is aneural (8), the evidence is largely against them (1, 7, 9, 10, 11). As an example, the 1987 text edited by rheumatology professor Malcolm Jayson, MD, titled The Lumbar Spine and Back Pain, states “the mature human spine has no nerve endings of any description in the nucleus pulposus or annulus fibrosis of the intervertebral disc in any region of the vertebral column.” (8)

In summary, there is good evidence that the annulus of the intervertebral disc is innervated with sensory nociceptive nerves, and the annulus of the intervertebral disc is “the site” of chronic low back pain:

• The intervertebral disc is innervated with nociceptors.
• The intervertebral disc itself is capable of producing low back and leg pain.
• The intervertebral disc is probably the most frequent source of chronic low back pain.

••••••••••

The Magnitude of the Chronic Low Back Pain Problem

Chronic pain in America is epidemic. Recent evidence suggests that of the 238 million adults in the US, 116 million suffer from chronic pain (12, 13). Quantifying the anatomical regions for American’s chronic pain shows that more than a quarter of chronic pain is located in the low back (14):

Hip Pain 07.1%
Finger Pain 07.6%
Shoulder Pain 09.0%
Neck Pain 15.1%
Severe Headache 16.1%
Knee Pain 19.5%
Lower-Back Pain 28.1%

Low back pain is one of the most thoroughly investigated health problems worldwide. Suffering with low back pain is almost a universal human experience. The United Stated Government’s National Institutes of Health (NIH) has the National Institute of Neurological Disorders and Stroke, which has a Low Back Pain Fact Sheet (15). The Fact Sheet makes the following key points:

• Nearly everyone at some point will have back pain.
• Americans spend at least $50 billion each year on low back pain.
• Back pain is the most common cause of job-related disability and a leading contributor to missed work.

Public Health statistics add the following key points (16):

• Low back pain (LBP) is a major public health problem worldwide.
• All age groups are affected with low back pain, including children and adolescents.
• 1%–2% of adults in the United States are disabled with low back pain.
• The morbidity toll attributed to low back pain is enormous from both personal and societal perspectives.
• Direct back pain health-care expenditures in the United States were $90.7 billion in 1998. The burden is even greater when indirect costs such as productivity losses, indemnity pay, litigation, retraining and other administrative costs are considered.
• Only heart disease and stroke have substantially higher medical expenditures than spine disorders in the United States.
• LBP is presently the leading cause of disability in the world.
• LBP is the leading cause of activity limitation and workplace absence in most parts of the world.
• Most people will experience LBP at some point in their lifetime, with two-thirds having a recurrence and one third having periods of disability.
• Cases in which LBP never recurs are rare.
• A previous episode of back pain is the primary risk factor for a new LBP episode.

••••••••••

For decades, conventional wisdom pertaining to Low Back Pain (LBP) has been that the great majority (90%) of those suffering with it will resolve quickly (within two months) with no treatment or with any form of treatment. This “wisdom” was published early on by the spine care pioneer Alf Nachemson, MD, PhD, in the debut issue of the journal SPINE in 1976. Dr. Nachemson stated (4):

“Irrespective of treatment given, 70% of [back pain] patients get well within 3 weeks, 90% within 2 months.”

A few years later (1979 first edition, 1990 second edition), the reference text Clinical Biomechanics of the Spine, was published and stated (17):

“There are few diseases [low back pain] in which one is assured improvement of 70% of the patients in 3 weeks and 90% of the patients in two months, regardless of the type of treatment employed.”

This “quick recovery regardless of treatment conventional wisdom” pertaining to low back pain was challenged in 1998 by Peter R. Croft, PhD, and colleagues. Dr. Croft is a Professor of Primary Care Epidemiology at Keele University in Staffordshire, UK. Dr. Croft and colleagues published their work in 1998 in the British Medical Journal in an article titled (18):

Outcome of Low back Pain in General Practice: A Prospective Study

These authors evaluated the statistics on the natural history of low back pain, noting that it is widely believed that 90% of episodes of low back pain seen in general practice resolve within one month. They consequently investigated this claim by prospectively following 463 cases of acute low back pain for a year.

These researchers discovered that 92% of these low back pain subjects ceased to consult their primary physician about their low back symptoms within three months of onset; they were no longer going to their doctor for low back pain treatment. Yet, most of them still had substantial low back pain and related disability. Only 25% of the subjects who consulted about low back pain had fully recovered 12 months later; 75% had progressed to chronic low back pain sufferers, but they were no longer going to their doctor!

Dr. Croft and colleagues note that NOT seeing a doctor for a back problem does NOT mean that the back problem has resolved. This study showed that 75% of the patients with a new episode of low back pain have continued pain and disability a year later, even though most are not continuing to go to the doctor. They conclude that the belief that 90% of episodes of low back pain seen in general practice resolve within one month is false.

In 2003, Lise Hestbaek, DC, PhD, and colleagues from the University of Southern Denmark published a study in the European Spine Journal, titled (19):

Low back pain: what is the long-term course? A review of studies of general patient populations

These authors performed a comprehensive review of the literature on this topic, noting “it is often claimed that up to 90% of low back pain (LBP) episodes resolve spontaneously within 1 month.” They used 36 articles that met their criteria. The tabulated results showed that 62% on average (range 42-75%) still experienced pain after 12 months. The authors concluded:

“The overall picture is that LBP does not resolve itself when ignored.”

“The overall picture is clearly that LBP is not a self-limiting condition. There is no evidence supporting the claim that 80–    90% of LBP patients become pain free within 1 month.”

Ronald Donelson, MD, is a Board Certified Orthopedic Surgeon and the current Vice President of the American Back Society. Dr. Donelson is associated with the State University of New Youk, in Syracuse. In 2102, Dr. Donelson and colleagues published a study in the journalPhysical Medicine and Rehabilitation, titled (20):

Is It Time to Rethink the Typical Course of Low Back Pain?

The purpose of this study was to determine the frequency and the characteristics of low back pain (LBP) recurrences. Questionnaires were given to 589 LBP patients from 30 clinical practices (primary care [7%], physical therapy [67%], chiropractic [19%], and surgical spine [7%]) in North America and Europe. The results were:

1) Are low back pain (LBP) recurrences common?: [rounded]

73% had suffered a previous episode of LBP

54% had experienced ≥10 episodes of prior LBP in their lifetime

20% had experienced >50 episodes of prior LBP in their lifetime

27%  with a previous episode of LBP had 5 or more episodes of LBP per year

2) Do LBP episodes worsen with multiple recurrences?: [rounded]

61% reported in the affirmative

Dr. Donelson and colleagues are critical of clinical practice guidelines that characterize the typical course of LBP as benign and favorable, stating:

“It is often stated that LBP is normal; has an excellent prognosis, with 90% of individuals recovering within 3 months of onset in most cases; and is not debilitating over the long term.”

“In any one year, recurrences, exacerbations, and persistence dominate the experience of low back pain in the community. This clinical picture is very different from what is typically portrayed as the natural history of LBP in most clinical guidelines.”

“Consistent with many other published studies, the recurrence rate among our respondents with LBP was 73%.”

“Many patients with chronic LBP had prior recurrent episodes that had become longer and more severe until the most recent episode did not resolve and thus became chronic.”

“Collectively, our findings, and those of other studies, indicate that it may be inaccurate to characterize LBP as having an excellent prognosis. Recurrences are frequent and are often progressively worse over time. Recovery from acute LBP is not as favorable as is routinely portrayed.”

“Eventually, there may be no recovery, and the underlying condition may become chronically painful. In light of these characteristics, it seems inappropriate to characterize the natural history of LBP as benign and favorable.”

••••••••••

In 2013, Coen J. Itz, PhD, and colleagues from the Department of Health Service Research, Maastricht University, The Netherlands, published a study in the European Journal of Pain, titled (21):

Clinical Course of Non-Specific Low Back Pain: A Systematic Review of Prospective Cohort Studies set in Primary Care

Dr. Itz and colleagues performed a systematic literature review investigating the clinical course of pain in patients with non-specific acute low back pain that obtained treatment in primary care. All included studies were prospective studies, with follow-up of at least 12 months. Proportions of patients still reporting pain during follow-up were pooled. A total of 11 studies were eligible for evaluation. The pooled proportion of patients still reporting pain after 1 year was 71%. These authors state:

“Non-specific low back pain is a relatively common and recurrent condition for which at present there is no effective cure.”

“In current guidelines, the prognosis of acute non-specific back pain is assumed to be favorable.”

“The findings of this review indicate that the assumption that spontaneous recovery occurs in a large majority of patients is not justified.”

Kate Dunn, PhD, is an epidemiologist working at the Arthritis Research UK Primary Care Centre, Keele University, Staffordshire, UK. In 2013, Dr Dunn and colleagues published a study in the journal Best Practice & Research Clinical Rheumatology, titled (22):

Low Back Pain Across the Life Course

Dr. Dunn and colleagues note that people with back pain continue to have it on and off for years. They state:

“Back pain episodes are traditionally regarded as individual events, but this model is currently being challenged in favor of treating back pain as a long-term or lifelong condition. Back pain can be present throughout life, from childhood to older age, and evidence is mounting that pain experience is maintained over long periods.”

Dr. Dunn and the other articles referenced above all make the same central points. They are, as a rule, acute non-specific low back pain is not self limiting, it is more likely than not to become chronic, when it becomes asymptomatic recurrences are very common, each recurrence tends to become worse, and the solution is to administer a long-term management strategy that alters the pathophysiological process.

••••••••••

Hyper-innervation, Neoneuralisation, Receptive Field Enlargement

So, what is going on? What is happening? Why is the intervertebral disc not following the “rules” of healing that other tissues of the body follow?

Undoubtedly, chronic and recurrent low back pain is multifactorial, involving genetics, inflammatory profile, uniqueness and number of injuries, occupation, recreational activities, age, gender, nutrition, etc. Starting about 2 decades ago, a unique explanation for back pain and chronicity began to emerge: more pain nerves grow into the disc.

Today there is almost universal acceptance that the annulus of the intervertebral disc is innervated with pain afferents and the annulus of the disc is the most probable source for low back pain. There was also 100% agreement that these nerves are only found in the annulus, and that the nucleus was aneural (has no nerve supply and therefore cannot initiate a pain response to the brain). However, an important addition to these concepts arose in 1997.

•••••

In 1997, AJ Freemont and colleagues published a study in the journal Lancet, titled (23):

Nerve Ingrowth Into Diseased Intervertebral Disc in Chronic Back Pain

Using samples of the intervertebral discs from 38 humans, these authors were able to show that when the disc degenerates, the nerves in the annulus can migrate into the nucleus. Histologically, these nerves in the nucleus were judged to be pain afferents. Thus the nucleus itself could be a source of discogenic pain. These authors used these anatomical findings to explain why low back pain can be so chronic, and continue to add to the evidence that the disc is the primary source of low back pain.

•••••

Also in 1997, in the journal Spine, another study was published on the topic of nucleus innervation by MH Coppes and colleagues from the Department of Neurosurgery, Groningen University, The Netherlands. Their article was titled (24):

Innervation of “Painful” Lumbar Discs

These authors note that the innervation of intervertebral discs has been extensively described in fetal and adult animals and humans. However, little is yet known about the innervation of severely degenerated human lumbar discs. They question whether a disc that has been removed for low back pain possesses an increased innervation compared with normal discs.

They investigated the innervation of discographically confirmed degenerated and “painful” human intervertebral discs to determine the type and distribution patterns of nerve fibers present. Their investigation used immunocytochemistry from 10 degenerated and 2 control human discs.

In all specimens, nerve fibers of different diameters were found in the anterior longitudinal ligament and in the outer region of the disc. In 8 of 10 degenerated discs, fibers were also found in the inner parts of the disc. The authors concluded:

“Findings indicate a more extensive disc innervation in the severely degenerated human lumbar disc compared with normal discs. The nociceptive properties of at least some of these nerves are highly suggested by their substance P immunoreactivity, which provides further evidence for the existence of a morphologic substrate of discogenic pain.”

•••••

In 2002, AJ Freemont and colleagues from Manchester University, UK, published a study in the Journal of Pathology, titled (25):

Nerve Growth Factor Expression and Innervation of the Painful Intervertebral Disc

In this study, the authors used immunohistochemistry analysis of painful human intervertebral discs to determine the presence of nerve growth factor. Such a finding would support the growth of nociceptors into deeper layers of the annulus, accounting for increased discogenic pain. The authors concluded:

“These findings show that nociceptive nerve ingrowth into painful intervertebral disc is causally linked with nerve growth factor production.”

•••••

In 2002, J. Melrose and colleagues from the University of Sydney, published a study in the journal Spine, titled (26):

Increased Nerve and Blood Vessel Ingrowth Associated with Proteoglycan Depletion in an Ovine Annular Lesion Model of Experimental Disc Degeneration

These authors note that following intervertebral disc injury, there is a loss of disc proteoglycans and disc degeneration ensues. The aim of this study was to evaluate whether disc nerve ingrowth was associated with proteoglycans depletion and disc degeneration. They used a sheep injury model, and like other studies assessed the injured tissues using immunohistochemistry. The injured discs were assessed at 3, 6, 12, and 26 months. They confirmed that disc injury results in degeneration, a loss of proteoglycans, and an ingrowth of nerve fibers. Importantly, nerve ingrowth could take 12 months to achieve a meaningful level; this may explain why increased or chronic back may be delayed following an disc injury. The authors concluded:

“Nerve and blood vessel ingrowth into the annulus fibrosis were strongly associated with proteoglycan depletion.”

•••••

In 2005, B. Peng and colleagues from the Department of Orthopaedics, 304th Hospital, Beijing, China, published a study in the journal Journal of Bone and Joint Surgery, British, titled (27):

The Pathogenesis of Discogenic Low Back Pain

These authors note that discogenic low back pain is a common cause of disability. They state, “discogenic low back pain is non-radicular and occurs in the absence of spinal deformity, instability and signs of neural tension. It arises from the disc itself.” They collected 19 specimens of lumbar intervertebral discs from patients with discogenic low back pain. Once again they used immunohistochemistry to evaluate disc fibers.

The authors found a distinct histological characteristic of the painful disc: there were more nerve fibers in the painful discs than in the control discs. Importantly, the painful discs showed ingrowth of nerve into the nucleus pulposus in 32% of specimens. The authors state:

“Our findings suggest that pain may arise from the nucleus pulposus due to innervation accompanying the ingrowth of granulation tissue.”

•••••

In 2012, Manos Stefanakis, PT, PhD, and colleagues from the Centre for Comparative and Clinical Anatomy, University of Bristol, Bristol, United Kingdom, published a study in the journal Spine, titled (28):

Annulus Fissures Are Mechanically and Chemically Conducive to the Ingrowth of Nerves and Blood Vessels

These authors note that it has long been suspected that lumbar intervertebral discs are a common source of the most severe symptoms of chronic low back pain. They state, “discogenic back pain is closely associated with fissures in the annulus fibrosus, and with the ingrowth of nerves and blood vessels.”

These authors completed a mechanical and biochemical analyses of human cadavers and surgically removed discs to test the hypothesis that fissures in the annulus of degenerated human discs are mechanically and chemically conducive to the ingrowth of nerves and blood vessels. They conclude:

“The two features most strongly associated with discogenic back pain—annulus fissures and nerve ingrowth—may themselves be causally related. It has long been supposed that discogenic back pain can arise from nerves growing into radial fissures.”

“Nerves do grow into fissures in patients with back pain.” 

“The present study has shown that annulus fissures are conducive to the ingrowth of nerves and blood vessels.”

It appears that “annulus fissures are indeed essential for nerve ingrowth into degenerated discs.”

•••••

Summary

The intervertebral disc is innervated with an extensive array of pain nerves. With disc degeneration, there is an increase in the number of pain nerve fibers migrating deeper into the disc, including into the nucleus itself. The increase in the number of pain nerve fibers increases the likelihood that stress and injury will produce low back pain.

Improving mechanical integrity of the spine initiates a neurological sequence that inhibits chronic low back discogenic pain; it “closes the pain gate.” This is the clinical goal of chiropractic spinal manipulation (adjusting) (29). Many studies show that chiropractic spinal adjusting is both effective and has long-lasting clinical improvement in the management of the chronic low back pain patient (29, 30, 31, 32, 33).

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