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10 Articles in Volume 16, Issue #5
A Review of Skeletal Muscle Relaxants for Pain Management
Applying Kinesiology as a Multi-Prong Approach to Pain Management
Arachnoiditis: Diagnosis and Treatment
Bench to Bedside: Clinical Tips from APS Poster Presentations
Conversation With David Williams, PhD, President of the American Pain Society
Letters to the Editor: Prince Fentanyl Overdose, High-Dose Opioids, Mystery Care
Los Angeles Times Versus Purdue Pharma: Is 12-Hour Dosing of OxyContin Appropriate?
My Experience With OxyContin 12-Hour Dosing
Technology: Changing the Delivery of Healthcare
The Neuroscience of Pain

Arachnoiditis: Diagnosis and Treatment

Arachnoiditis has traditionally been considered a rare, hopeless disease, but it is now emerging as relatively common entity that can be treated.

Arachnoiditis is a progressive neuroinflammatory disease.1-3 Although recognized many years ago, heretofore it has been considered a rare disease and is listed in the “Rare Disease Registry.”2,3 I first introduced readers to the term adhesive arachnoiditis (AA) in the August 2014 issue of Practical Pain Management.3 Today, we expand our coverage of the condition, which is, for many reasons, increasing in incidence and prevalence.

Although the term arachnoiditis simply implies inflammation of the arachnoid lining of the meninges or thecal sac, the major pathologic abnormality in the majority of cases is neuroinflammation of the nerve roots in the cauda equina.4-8 Once glia cells in nerve roots produce neuroinflammation, they may form adhesions and scars that may cause nerve roots to stick together or clump and adhere to the arachnoid lining.9-13

Glial cell activation in the nerve roots of the spinal cord produces neuroinflammation, adhesions, and scarring.

The term AA is the term historically assigned to the condition when adhesions or scarring between nerve roots and/or the arachnoid lining is visible on magnetic resonance imaging (MRI).2,12 AA will be the term used throughout this paper as it is this stage of the disease that usually causes a patient to seek medical and pain treatment.

Although neuroinflammation and adhesion formation may naturally resolve in some patients, AA may be a crippling, progressive, painful condition of immense severity.6,14-17 It may progress to lower extremity paralysis; bladder, bowel and gastrointestinal dysfunction; inability to sit or stand for long periods of time; deterioration of mental abilities; and create an autoimmune disorder with symptoms that mimic classic rheumatologic disease.3

Over the past 5 years, my clinic has admitted to treatment an increasing number of patients with AA. Today, the practice follows about 65 cases. I have reviewed the MRI’s from over 200 confirmed patients. Some of the cases were accepted as emergencies because they developed severe pain and partial paralysis of the lower extremities and bladder dysfunction immediately after a spinal tap, epidural anesthesia given for childbirth, epidural corticoid injection, or surgery.  

Little has been written about the clinical diagnosis and treatment of arachnoiditis.2,3 Much of what is written here is the author’s personal observations, beliefs, and methods as there are few supporting references in the literature.

Anatomy of the Spinal Cord

Understanding AA requires some knowledge about the anatomy of the cauda equina, or “horse’s tail.” About two dozen nerve roots emanate and hang down from the end of the spinal cord known as the conus medullaris (Figure 1).18,19 The nerve roots within the thecal sac are quite organized. They are primarily in the posterior portion of the thecal sac between L1 to L3 and then move forward or anterior (Figures 2 and 3). The nerve roots progressively exit the thecal sac beginning between L1 and L3.  

Nerve roots of the cauda equina are constantly bathed and submerged in spinal fluid that acts as a lubricant against friction between nerves, transports waste products, and brings nutrients to the nerve roots.20-24 The spinal fluid turns over about 4 times a day.20 Therefore, waste products, including inflammatory particles from inflamed nerve roots, are carried upward to drain through channels in the meninges into cervical lymph nodes and general circulation.21-23

To illustrate how neuroinflammation affects the spinal cord, we turn to a rare, but devastating example. Cauda equina syndrome is a serious neurological emergency that can have devastating long-lasting neurologic consequences. This diagnosis is given when anatomical tissue, from a malignant mass or an intervertebral disc or collapsed vertebrae, acutely compresses the nerve roots of the cauda equina. When cauda equina compression occurs, it is a neurosurgical emergency because the nerve roots must be released to prevent lower extremity paraparesis, paralysis, bladder and bowel impairment, and severe pain.  

Although the term cauda equina syndrome has traditionally only referred to the acute compression of the nerve roots, some practitioners have used the term “chronic cauda equina syndrome” when bladder and bowel dysfunction, pain, and some paraparesis coexist.25-27 In addition, cauda equina syndrome is a rare but well-recognized complication of longstanding ankylosing spondylitis. A number of case reports have shown linked arachnoiditis in the pathogenesis of the cauda equina syndrome of ankylosing spondylitis.28,29 As far as I can determine, the term chronic cauda equine syndrome is not due to nerve root compression but, rather, neuroinflammation of the nerve roots in the cauda equine—in effect, it may be considered an alternate name for AA.

The Inciting Cause: Irritation and Neuroinflammation    

AA is primarily found in the lumbar-sacral spine, although it also may occur in the cervical and thoracic spines.7,9,10,16,17,30 Traditionally, the diagnosis of AA has been made on MRI, where nerve roots in the cauda equina can be seen to have formed adhesions between each other, forming clumps, and/or when adherence to the arachnoid lining is caused by adhesions.5-11

AA may originate with any irritant that may affect some of the 2 dozen nerve roots in the cauda equina.14,31 The irritant may be a toxin, trauma, infection, or friction between nerve roots.4,10,12,15,31 Once irritation occurs in the nerve roots, activated glial cells initiate a neuroinflammatory response.32-34 Like all inflammation, a modest amount is protective and curative, but too much causes tissue destruction with adhesive and scarring elements.  

Common pathologic conditions of the spine, including herniated discs, spinal stenosis, and degenerative arthritis, may cause enough irritation to produce neuroinflammation in cauda equina nerve roots in the lumbar region. Despite the lubricating properties of spinal fluid, spine deformities and imbalances produced by scoliosis, cysts, or arthritis may cause enough compression and friction between nerve roots to cause irritation, activation of glia cells, and neuroinflammation.

The trauma of medical procedures, including paraspinal injections and surgeries that are medically indicated, may leave AA behind as a complication.4,6,15,17,25,26  Although the percentage is unknown, many patients who are now labeled with “failed back surgery syndrome” likely have AA and should be evaluated for this condition.

Pathologic Progression and Diagnosis

Unfortunately, AA may develop, resolve, and become a progressive, debilitating disease.2,3,7,10,11,13 The inflamed nerve roots and arachnoid lining may progressively inflame and add or “capture” additional nearby nerve roots. The progression may go up or down the spine. For example, what may start out as mild pain with some bladder or bowel dysfunction with mild headache may progress to an inability to urinate without catheterization and lower limb paralysis.  

A significant number of AA patients have presented to my clinic with advanced disease. They may have already progressed to the point that a walker or wheelchair was necessary to ambulate. Some severe patients literally have so much pain, fatigue, and disability that they report to me that they spend 80% to 90% of their time in bed. Some patients report that pain is so excruciating that high-dose opioids are required for even a modicum of pain control.

Although the mechanism is somewhat unclear, patients may apparently develop some interference with spinal fluid flow.20,24 The cause, in my opinion, is that nerve root clumping, scarring, and adhesions form a physical “road block” for fluid flow. In addition to adhesions and scarring, AA patients may develop some interference with spinal fluid flow.20,24 Whatever the mechanism, patients may develop periodic blurred vision and severe headaches due to increased fluid pressure.2 Mental impairment and deterioration relative to attention span, memory, logistical or abstract thinking, and even reading and writing may occur. Some advanced stage AA patients develop such mental and physical debility that they require constant caretaking.2,3,10-13

Patients develop a high prevalence of arthralgia, myalgia, and such autoimmune phenomenon as Hashimoto’s thyroiditis and carpal tunnel syndrome.2,10,11,13  Although the mechanism for the development of autoimmune symptoms is unknown, a possible explanation is the drainage of cells and soluble antigens in the spinal fluid into regional lymph nodes.21-23 A major treatment goal is to stop the progression, disability, and deterioration that is characteristic of AA patients.

Diagnosis: Symptoms and Signs

AA patients have typical symptoms and signs that allow a practitioner to differentiate an AA patient from other back pain patients (Table 1).30 In addition to constant pain, in my experience over 90% of patients complain of (1) bladder dysfunction; (2) inability to stand more than a few minutes; (3) burning soles of feet; (4) episodes of blurred vision; (5) headache; (6) lacerating or stabbing pain in the legs; and (7) bizarre feelings on the skin (eg, bug crawling, water dropping, pins sticking). In my experience, the inability to stand very long is so dominant in these patients that they may even ask to lie on your exam table or on the floor of your office.  

Some physical signs of AA include lower extremity weakness, hyporeflexia, and abnormal gait.  Patients may not be able to do straight leg raises or flex one or both feet. Range of motion of both upper and lower extremities may be restricted. When their gait is observed, look for short steps, leaning, wide base, and unsteadiness.

Inflammatory Markers

In my experience, 30% to 40% of AA patients demonstrate elevated erythrocyte sedimentation rates (ESR) or high sensitivity C-reactive protein (CRP) levels.31,32 CRP levels may be exceedingly high. Other less known inflammatory markers such as the interleukins, myeloperoxidase (MPO), a1-antitrypsin, and tumor necrosis factor may also be elevated.31

Although the presence of elevated inflammatory markers may indicate more active or severe disease, this may not necessarily be the case. Neuroinflammation, like joint inflammation, may wax and wane. It may accumulate or dissipate for unknown reasons that may not equate to disease severity. The presence of an elevated ESR or CRP suggests, however, that AA is active and in need of treatment.32

Whether neuroinflammation can ever be totally arrested or “cured” is unknown. Considering that AA patients have constant pain and intermittent flares suggests that patients continually carry both neuroinflammatory and neuropathic components to their pain.

Magnetic Resonance Imaging (MRI)

The best MRI image to confirm a diagnosis of AA is usually the axial view of a contrast MRI (Figure 2) at the L3,L4,L5 and S1 levels of the lumbar spine.18,19 Pathologic changes in nerve roots can best be visualized by size and placement in the axial view of a contrast MRI.18 Figure 3 includes diagrams of the cauda equina nerve roots in their normal size and location. Inflamed nerve roots on an axial view appear as enlarged (edema), displaced from their normal position, and glued or clumped together (Figure 4). These MRI images show the 3 key signs of nerve root inflammation: (1) displacement; (2) enlargement; and (3) clumping. Some, but not all, radiologists will issue a diagnosis of arachnoiditis when these 3 signs are present. Technically, however, when adhesions to the arachnoid lining are not observed a more specific diagnosis might be cauda equina neuroinflammation.14

Figure 5, shows typical examples of clumped nerve roots within the spinal canal as well as adherence to the arachnoid lining. A major message I wish to convey is to not ask a radiologist to interpret an MRI without the clinical history. The radiologist should be sent a short clinical summary that states the situation such as: “This patient has urinary hesitancy, lower extremity pain, weakness, and has signs and symptoms that are compatible with adhesive arachnoiditis.” In summary, the MRI should confirm the diagnosis of AA and not be relied upon as the sole determinant. For example, some patients may show clumping with few or no clinical symptoms while others may have severe symptoms with questionable or marginal clumping.


My clinic has developed treatment protocols for both acute and chronic cases. The protocol comprises 4 components: (1) control and suppression of neuroinflammation; (2) exercises to prevent adhesions; (3) pain relief; and (4) neuroprotection and neurogenesis (nerve growth) (Table 2).33-63 The most critical component of treatment is suppression and control of neuroinflammation; otherwise, AA may progress and worsen.  

It is my personal observation that stable pain relief is difficult to attain in AA patients until a potent and aggressive neuroinflammation regimen is in place. The neuroinflammation regimen recommended here may first appear to have undue risks, but less potent attempts by my team have not been successful. For example, only 2 traditional anti-inflammatory agents have shown effect in our hands: ketorolac and indomethacin.40,41 Ketorolac cannot be used for over 5 consecutive days or on a daily basis with pentoxifylline. This regimen was developed, in part, by finding very low serum cortisol levels late in the day and evening in AA patients and the presence of inflammatory markers that did not decrease with most anti-inflammatory agents.31

Studies in rats have shown that the corticosteroid, methylprednisolone, and the anti-inflammatory agent indomethacin suppress cauda equina inflammation and adhesion formation.40,41 Microglial activation and neuroinflammation formation has, in rats, been shown to be suppressed by: acetazolamide; minocycline; and pentoxifylline.42-63 Acetazolamide may also lower spinal fluid pressure as an added benefit. Due to the well-known side effects of indomethacin, ketorolac, and corticosteroid drugs, we do not recommend daily but intermittent administration in an effort to avoid side effects while keeping nerve roots from forming additional adhesions and scars which may cause neurologic impairments. Periodic assessment of renal function is essential with ketorolac administration, and it will have to be discontinued if renal function is adversely affected as indicated by elevated levels of creatinine or blood urea nitrogen, or reduced glomerular filtration rate.    

Pain control in AA is essentially the same as for any patient with severe, intractable pain. Practitioners have a number of neuropathic and opioid agents from which to choose. At this juncture the author has seen success with a number of pain control regimens and agents. The goal of pain relief, particularly opioids, is to provide enough pain relief for the patient to exercise and walk daily, carry out activities of daily living, and escape a bed-couch bound state. Severe cases may require high-dose opioid therapy.  

In cases where opioids have not been needed, low-dose naltrexone (1 to 5 mg a day) has been effective in my hands. To enhance pain relief and minimize opioids, the use of ketamine, adrenergic agents, and topical anesthetics have been helpful.37-39 A sleep aid may be necessary to not only induce sleep but to assist CNS lymphatic drainage.36

Exercises are essential to prevent spinal nerve roots from clumping, scarring, and forming adhesions that can lead to lower extremity paraparesis and/or paralysis. The message is simple, keep exercising or become paralyzed. We teach patients to stretch both upper and lower extremities several times a day. Straight leg raising and foot flexing will put some stretch on nerve roots. Knee bending and raising the leg toward the abdomen while either lying down or standing is necessary. Walking outside the house each day is mandatory. Water immersion is highly recommended, as it allows better stretching and pain relief.  Gently bouncing on a trampoline or rocking in a chair provides comfort and hopefully increases spinal fluid flow.

A number of measures are recommended to hopefully promote neuroprotection and neurogenesis (nerve growth) of damaged nerve roots: replacement of deficient hormones; use of the neurohormones, human chorionic gonadotropin and oxytocin; high-protein/anti-inflammatory diet; vitamin B12; and pentoxifylline with tocopherol (vitamin E).

As noted, the dual concepts of neuroprotection and neurogenesis are essential for the management of AA. Unfortunately, the nerve roots in the cauda equina are anatomical strings that are freely suspended in fluid. Their lining is fragile. Once inflammation involves some of the nerve roots, it clinically appears to be capable of spread as AA patients recurrently claim that they may worsen following additional trauma, medical procedures (including physical manipulation and paraspinal injections), and even infections.  

Given this clinical observation, neuroprotection seems as equally important as is neurogenic efforts to repair and regrow damaged and inflamed nerve roots. The combination of pentoxifylline and vitamin E has been reported to dissolve fibrotic scars and adhesions when given over a period of several months.64-66 Pentoxifylline is not only a microglial cell inhibitor but it is theorized to alter the shape of red cells and carry vitamin E into the scarred or fibrotic tissue and eventually dissolve it. The use of pentoxifylline was initiated by French physicians, and I have also found this treatment to be remarkably effective in select cases.  

Emergency Treatment for Acute AA

Arachnoiditis may acutely appear after a single spinal tap, epidural anesthesia, epidural corticosteroid injection, surgery, trauma, or viral infection. Pain practitioners need to be aware of this possibility and be prepared to provide emergency treatment to prevent severe disability and impairment. Patients who develop acute arachnoiditis complain of severe back pain, leg weakness or radiculopathy, and possibly bladder impairment within 24 hours (sometimes within minutes to an hour) after the inciting event (Figure 6). If the patient presents within the first 90 days after the event, emergency treatment is recommended (Table 3). To illustrate, a case report is given here with the patient’s chronic management program included.

Case Report

A 23-year-old Hispanic woman in good health except for scoliosis had epidural anesthesia during childbirth.  Within a few hours after delivery of the baby, the patient developed severe lumbar back pain, headache, and great difficulty with ambulation. Symptoms progressed over the next 30 days to the point of frequent leg tremors, increased difficulty with walking and standing, and difficulty urinating.  

An MRI showed arachnoiditis and she was referred to my clinic. Physical examination revealed labored gait, hypoactive leg reflexes, and inability to perform straight leg raise. She was started on a 6-day methylprednisolone dose pack and a ketorolac injection (60 mg) for 3 consecutive days. She was prescribed hydrocodone/acetaminophen 10 mg every 4 to 6 hours, and acetazolamide 125 mg a day and minocycline 100 mg twice a day. Within a week she was markedly improved. Within 90 days she was put on the medical regimen shown in Table 2. After 9 months her gait appears normal.  

The patient has some residual, intermittent pain and her ability to perform straight leg raises still shows minor impairment. Her specific regimen at the time of this writing includes: methylprednisolone 4 mg at 3:00 pm 5 days a week; ketorolac 30 mg IM every Monday; pentoxifylline 400 mg BID; oxycodone/acetaminophen 10 mg only as needed; ketamine 25 mg sublingual as needed for pain; and human chorionic gonadotropin 250 to 500 units taken 3 times a week. Her MRI (Figure 5, C) is still abnormal. She is able to hold a full-time job and care for her children. She will be followed indefinitely.  


Nerve roots in the cauda equina can become inflamed if they are irritated for any reason, including toxins, infections, trauma, or friction between roots. The most common initiating causes are probably herniated discs that compress nerve roots. Degenerated arthritic joints, trauma, or scoliosis that cause friction or compression between some of the nerve roots also may cause AA. Medical procedures required to treat spinal pathologic abnormalities may accelerate or possibly initiate a neuroinflammatory process in cauda equina nerve roots.  

AA appears to be increasing in prevalence and cases are now being seen throughout the United States. Patients who are labeled “failed back surgery syndrome” undoubtedly have a very high prevalence of AA. Pain produced by AA may be profound, and any back pain patient who voices severe pain complaints, requires analgesia above the norm, and complains of paraparesis, inability to stand, blurred vision, burning feet, or bowel/bladder dysfunction should be suspected of having AA. The diagnosis of AA is made by history, physical, and a confirmatory MRI. Medical protocols for acute and chronic AA have been developed and are published here for utilization in ambulatory care settings. Aggressive treatment should be started as soon as arachnoiditis is suspected to stop or slow its progressive, debilitating nature. Further research will be done to follow these patients and report on their progress.

Last updated on: September 28, 2017
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