Paul J Christo and Peter S Staats

The Peripheral Neuropathy Solution

Neuropathy Solution Program

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When did the pain start? Where does it hurt? What sort of pain is it? How much does it hurt? The answers to these questions provide important clues to why a person is in pain. Unfortunately, we must rely on the patient's information about the when, where, what, and how of pain to shed light on the biological basis of most pain conditions. On the other hand, we understand the interaction of various aspects of pain sufficiently to reveal when a patient may be malingering for financial or emotional gain or to decide which tests may allow us to diagnose an underlying pain-generating condition or disease.

A multidisciplinary diagnostic effort by a trained team best serves patients suffering from chronic pain. After reaching a diagnosis, the team can determine the best strategy to treat the underlying disease and the pain.

Determining the source of spinal pain can be extremely challenging because of the vast number of structures that can generate pain. Pain can arise from bones, muscles, ligaments, nerve structures, and/or alterations in vascular supply. In addition, pain has numerous etiologies, ranging from structural malalignment to somatoform disorders.

The first step in determining the source of pain is to perform a thorough history and physical exam, to be supplemented with appropriate diagnostic tests to make an accurate diagnosis. Only then can we take the second step—determining which tool to use to help the patient with pain.

General contractors can build houses because they understand the jobs of the many specialists involved (e.g., electricians and plumbers). Pain physicians must also understand the tools in their toolbox and know when to apply them. These tools include medical management, physical medicine techniques, radiation and chemotherapeutic options, neuromodulation techniques (electrical stimulation and intraspinal infusion therapy), therapeutic neural blockade, anatomical procedures to fix structural abnormalities, and, of course, ablative techniques (Figure 3.1).

If physicians offer only interventional techniques, patients will not receive the most comprehensive care. On the other hand, if physicians

Epidurals _L-a—Pathways

Intrathecal ; Brainstem/; Opioids

Infusions I Spinal Cord! TCAs

Pain ; _ ] Pain transmission ----ts inhibition i!_-J—I

Figure 3.1. Targets for pain treatment: TCAs, tricyclicanti-depressants; NMDA, N-methyl-D-aspartate. (Adapted by Peter S. Staats.)

Inhibit Prostaglandin Synthesis

NMDA receptor antagonists Prostaglandin synthesis inhibitors Dorsal root ganglionectomy

Epidurals _L-a—Pathways

Intrathecal ; Brainstem/; Opioids

Infusions I Spinal Cord! TCAs

Pain ; _ ] Pain transmission ----ts inhibition i!_-J—I

NMDA receptor antagonists Prostaglandin synthesis inhibitors Dorsal root ganglionectomy fail to offer interventional options, they are neglecting the most highly effective options. To minimize risk and discover the least invasive/ most successful treatment for a patient, we generally begin with the most conservative approaches (medical management, rehabilitation strategies, lifestyle changes, psychological approaches, and alternative strategies) and work our way up the continuum of complexity and risk to interventions like spinal cord stimulation and intrathecal drug delivery with an implanted pump. Conservative therapies can offer pain control without the risks associated with invasive techniques. Conservative therapies, however, do not always work and are not permanent. When conservative therapies fail or the side effects of these therapies become intolerable, a physician should consider use of an interven-tional technique (Figures 3.2 to 3.4).

This text concentrates on the importance of interventional techniques in the management of pain. Although each chapter highlights indications, techniques, outcomes, and complications, it is important to recognize that interventional therapies are not the only options for patients with pain. Before considering interventional techniques, an accurate diagnosis must be made, and conservative therapies should be considered, if not exhausted.

This chapter begins by reviewing the diagnostic tools that are invaluable in evaluating patients and identifying appropriate candidates for various therapeutic and palliative procedures: review of the patient's medical history, a thorough physical examination, imaging studies, elec-trodiagnostic tests, laboratory tests, and diagnostic nerve blocks. Finally, we discuss the appropriate role of interventional therapies.

History and Physical Examination

Reviewing a patient's medical history and conducting a thorough physical examination provide healthcare practitioners with vital informa-

Figure 3.2. The WHO ladder (revised by Peter S. Staats) for treatment of pain of terminal diseases.

Neuroablation

Interventional strategies

Non-opioid

Weak opioid ± adjuvant + non-opioid

Strong opioid + non-opioid

Figure 3.3. Neuropathic pain treatment algorithm.

Neuropathic Pain Algorithm

Consider adjuvant pharmaceutical (NM DA antagonists alpha-2 agonists)

Investigative Approaches t

Electrical Stimulation/IT Therapy t ^

Consider Opiate Therapy

Begin physical medicine •« approaches •Acupuncture •TENS

Nerve blocks

Evaluate and treat , comorbid disorders (i.e., depression)

Figure 3.4. Neuropathic pain treatment algorithm. TENS, transcuta-neous electrical nerve stimulation.

Chronic Pain t

Treat Underlying Cause t

Neuropathic Pain t

Diagnose Pain

Interventional strategies

Avoid dysfunction •Rehabilitation •Cognitive Therapy

Oral and IV local anesthetics

Topical analgesics i.e., capsaicin, lidocaine

Shooting or lancinating: anticonvulsants

Constant burning or concomitant depression: TCA's

Nonsteroidals, physical medicine approaches (heat, cold massage, rest), alternative therapies tion for making diagnostic and treatment decisions. We glean most of our information about a patient's medical history simply by asking the patient and/or the patient's family members pertinent questions. The asking part is easy. Knowing what to ask is harder and, of course, crucial. We can augment or confirm some aspects of the patient's medical history by asking the patient to bring a completed questionnaire to the initial appointment.

Recording and reviewing the patient's medical history highlights what we should expect and check for during the physical examination. This activity also helps establish a productive patient-physician relationship by assuring the patient of the physician's interest, which helps the physician gain the patient's trust and confidence. By providing a clear picture of the patient's functional status prior to the onset of pain, the history will also help define the treatment goal.

History Gathering

To obtain a patient's medical history, the physician must be a good listener and must direct the questioning appropriately to reveal and/or confirm vital information. Asking patients in pain the right questions will provide a clear picture of the onset and progression of the pain as well as the effect of the pain on each patient's daily life. These questions must elicit the chronology of events leading up to the consultation and must cover psychosocial and behavioral factors that affect the pain and interfere with the achievement of treatment goals. Thus, it is important to find out whether the patient likes his or her job, especially if the person is on disability leave and/or is receiving worker's compensation. It is also important to note the existence of pending litigation or other sources of secondary gain related to a patient's condition. Questions about the biological aspects of the pain should reveal:

Its location Its quality

Its intensity (measured on a scale) Its time course and whether it is constant What exacerbates it What alleviates it

Its effect, if any, on functional status

The clinician should review the results of any diagnostic tests or treatments for the pain (especially the efficacy, dose, frequency, and any side effect of pain medications and any psychological interventions) and gather information about the patient's general state of health, current medications, allergies (distinguishing between true drug allergies and transient adverse effects), sleep patterns (as a sign of possible emotional depression), and consumption of tobacco, alcoholic beverages, illegal drugs, drugs prescribed to another person, and over-the-counter medications. The history should also include information on any of the patient's childhood illnesses, physical and psychiatric adult illnesses, surgical procedures, major injuries, and hospitalizations that could affect the current pain problem.

Physical Examination

The patient's history and presenting complaint will indicate what needs to be assessed during the physical examination. In patients with unilateral limb pain, physicians should first examine the unaffected contralateral limb for comparison. The physician should inspect all areas where the patient feels pain for the presence of erythema, discoloration, abnormal nail growth, masses, induration, or scars. Light palpation of the painful area will reveal the presence of hyperalgesia. If the patient has symptoms of neuropathic pain, a thermal stimulus applied to the painful area will uncover thermal hyperalgesia.

If the patient has a lesion, palpation will indicate the presence of a mass and palpation-induced pain. Testing for sensory and motor function and deep tendon reflexes will uncover any involvement of peripheral nerves or nerve roots. In patients with neck or low back pain, it is important to examine the spine and determine range of motion. We may be able to determine where the pain originates (e.g., in such areas as the hip, sacroiliac joint, or lumbar spine) by performing appropriate procedures and maneuvers. Physicians can test for the presence of three or more of Waddell's signs (tenderness, simulation, distraction, regional disturbances, and overreaction) to determine whether low back pain is psychological in origin. The physical examination also provides an important opportunity to gauge the patient's mood, affect, and degree of pain behavior.

Imaging Studies

Imaging studies are crucial for identifying anatomical abnormalities that corroborate physical findings.

Conventional Radiographs

Because they can indicate whether a bone is healing and aligning properly or whether a patient has osteomyelitis or osteoporosis and can even reveal the coexistence of a pathological fracture and a destructive bond lesion, as well as size and shape of primary bone tumors, conventional radiographs are particularly helpful in diagnosing the cause of musculoskeletal pain in the back, neck pain, and pain in the limbs and/or joints.

Radiography is an extremely precise way to diagnose various arthritic disorders. Rheumatoid arthritis of the hands usually involves the meta-carpophalangeal joints, and a radiograph can reveal an incriminating narrowing of the joint space as well as articular surface erosions. Radiographs also reveal arthritic osteophytes (bony outgrowths) and sclerosis (scarring). Additional reasons for spine pain exposed by radiography include spondylolisthesis (when one vertebra has slipped over another), narrowing of disc space, kyphosis ("widow's hump"), scolio-sis (abnormal curvature of the spine), osteoporosis, hypertrophic spurs, failed spinal fusions, spondylosis (degeneration of one or more vertebrae), pars interarticularis defects (a break in the posterior elements of the spine), and zygapophyseal (facet) joint abnormalities. We can also use oblique x-rays to expose the neural foramina and flexion/extension views to assess spinal stability. Because this diagnostic tool is noninva-sive, most people with chronic pain accept it readily.

Myelography

Myelography may be used to confirm a diagnosis of a surgically correctable lesion, such as a herniated disk, and to pinpoint its exact location. It is less commonly used today but still helpful when primary screening with magnetic resonance imaging fails or cannot be used (as is the case when a pacemaker is present).

Computed Tomography Scanning (CT)

We use CT scans to evaluate the bony structures and soft tissues of the spine. Laterally placed fragments of herniated disc, for example, may be visible on a CT scan but missed on a myelogram. A CT scan provides important additional information when a herniated disc causes radicular pain by compressing a nerve root exiting through its neural foramen. Images of facet joints obtained by CT will reveal the degenerative and/or hypertrophic origin of chronic spinal pain, and axial CT scans provide three-dimensional images of spinal ligaments and discs.

Magnetic Resonance Imaging (MRI)

Presently, the single most important imaging tool for spine pathology, MRI provides a detailed image of the spinal cord, cerebrospinal fluid, extradural structures (intervertebral discs), and the patency of neural foramina. An MRI reveals disc degeneration, herniated discs, facet joint arthropathy, vertebra or disc infection, subluxation, stenosis, fracture, neoplasm, and vascular abnormalities.

Ultrasound

Although virtually useless for evaluating musculoskeletal pain, ultrasound is the best way to evaluate suspected gallbladder disease in patients with abdominal pain.

Bone Scanning

Bone scanning permits detection of the early stages and the course of bone metastasis, osteomyelitis, bone trauma, arthritis, hairline fractures, and all other diseases that involve bone turnover and can easily be missed by conventional radiography. Because bone scanning is nonspecific, however, diagnoses based on bone scans must generally be supported by appropriate clinical information and other imaging studies.

Thermography

Thermography may help diagnose neuromuscular and soft tissue disorders, especially in patients whose abnormalities elude detection during a physical examination. Some clinicians use thermography to evaluate:

Neuropathic syndromes (e.g., complex regional pain syndrome, radicular syndromes, peripheral neuropathies, carpal tunnel syndrome and other nerve entrapments, postherpetic neuralgia, thoracic outlet syndrome, and trigeminal neuralgia) Myofascial syndromes (e.g., fibromyalgia and lumbosacral strain) Circulatory disorders (e.g., peripheral vascular occlusive disease, va-

sospastic disease, and venous insufficiency) Skeletal disorders (e.g., osteomyelitis, lumbar facet syndrome, rheumatoid arthritis, scoliosis, and postfracture extremity pain)

Clinicians have not yet agreed upon the clinical applicability of ther-mography, and its use remains controversial and limited.

Electrodiagnostics

Electrodiagnostic studies provide information on how well nerve roots, peripheral nerves, and muscles are functioning. These diagnostic tools thus provide important information in suspected cases of nerve entrapment, radiculopathy, and peripheral neuropathy, to name a few. Specially trained physicians generally perform and interpret electro-diagnostic studies.

Electromyography (EMG)

Electrical potentials become abnormal in the presence of a diseased muscle or nerve serving a muscle. To discern the presence of abnormal potentials, one can record changes in intermuscular voltage on an electromyelograph. An oscilloscope displays activity measured by a monopolar needle electrode inserted in the muscle and by a surface electrode. A loudspeaker simultaneously amplifies the distinctive sounds of the muscle activity. We check for abnormal potentials during needle insertion and when the muscle is resting and contracting.

In a resting muscle, abnormal potentials can appear as fibrillation in a single muscle fiber with a disrupted nerve supply, positive sharp waves (a sudden move to the positive potential followed by a slow move to the negative), and/or fasciculation (spontaneous depolarization in a group of muscle fibers innervated by a single nerve fiber). Fibrillation potentials and positive sharp waves often occur simultaneously in the presence of radiculopathy and peripheral neuropathies, such as a diseased nerve plexus or degeneration of nerve axons, which cause muscle fibers to lose their normal innervation and undergo spontaneous depolarization. Because it can occur in healthy individuals, fas-ciculation must accompany fibrillation potentials and positive sharp waves to contribute to a diagnosis of neuropathic disease.

A normally active muscle, contracted minimally, will involve a single motor unit potential with four phases. A polyphasic potential, with five or more phases, may indicate neuropathic disease or myopathy. In the early stages of neural injury, however, neural conduction ve locity testing is more sensitive than EMG because EMG changes occur slowly over a period of weeks.

Nerve Conduction Studies (NCSs)

Nerve conduction studies, which use surface electrodes to stimulate a peripheral nerve and evaluate how well it is functioning, expose the abnormal nerve conduction that occurs during neuropathy as well as the location of a nerve lesion and/or nerve entrapment.

To perform motor NCSs, we stimulate a nerve to record a target distal muscle's evoked response (impulse velocity, amplitude, and latency—the interval after the stimulus and before the muscle contracts) and display these data on a monitor. To determine the velocity of a particular segment of a nerve, we stimulate the nerve at each end point of the segment and measure the latency from each point in an appropriate muscle. If we are examining the median nerve segment between elbow and wrist, for example, we can calculate conduction velocity by subtracting the distal latency (wrist to hand muscle) from the proximal latency (elbow to hand muscle) and then dividing the result into the distance between elbow and wrist.

To perform sensory NCSs, we place both a stimulating and a recording electrode over the target sensory nerve. We measure antidromic conduction (movement of impulses in the opposite direction to normal) by placing the stimulating electrode proximal to the recording electrode. We measure orthodromic conduction (movement of an impulse in the normal direction) by placing the stimulating electrode distal to the recording electrode. To calculate conduction velocity, we divide the distance between the electrodes by the latency time. Sensory NCSs may reveal peripheral neuropathies before a patient experiences significant sensory loss.

We can perform sensory and motor studies on the median, ulnar, radial, and tibial nerves. Additional sensory studies involve the lateral femoral cutaneous, sural, and superficial peroneal nerves, and we can conduct motor studies on the peroneal, sciatic, and other nerves.

Laboratory Tests

Laboratory tests can uncover abnormalities associated with many of the neurological diseases that present with pain. Obvious uses of laboratory tests include screening for diabetes, malnutrition, toxins, dys-proteinemia, cancer, and the thyroid disorders that can cause compression neuropathies. We can also detect abnormal inflammatory states or autoimmune dysfunction by checking a patient's erythrocyte sedimentation rate or levels of antinuclear antibodies.

Diagnostic Nerve Blocks

To perform a diagnostic nerve block, we inject a local anesthetic around a nerve proximal to a presumed pain-generating lesion. Our diagnosis depends upon whether this leads to pain relief. There are many variables to consider in the interpretation of the results of nerve blocks.

False positive results, for example, can be due to a placebo response or to the effect of systemically administered analgesics or a systemic uptake of local anesthetics. Other nonspecific effects may result from the needle placement or the effect of saline during a placebo test. It is also inappropriate to decide that just because a patient has responded to a placebo injection, the person's pain is psychogenic.

Peripheral Nerve Blocks

To determine whether peripheral nerves are the source of the pain, we inject local anesthetics around a nerve and assess the response. A report of a marked reduction in pain indicates that the pain is coming from a location distal to that nerve. (We must be mindful that the test can produce false positive results.) To block a sympathic nerve, we inject the local anesthetic onto the sympathetic chain at various sites. The primary sympathetic ganglia involved in pain include the stellate ganglion, the celiac plexus, the lumbar sympathetic ganglion, the superior hypogastric plexus, and the ganglion impar.

We use the stellate ganglion block to diagnose sympathetically mediated pain of the upper thorax, arm, head, or face and to treat postherpetic neuralgia, sympathetically maintained pain, or vaso-occlusive disease.

Celiac plexus blocks indicate whether pain is arising from the abdominal viscera and relieve pain caused by upper abdominal malignancies, including pancreatic cancer. A positive response to a celiac plexus diagnostic block is prognostic of several months of pain relief from celiac plexus neurolysis.

Lumbar sympathetic ganglion blocks allow us to diagnose sympathetically mediated pain of the lower extremities. Superior hypogastric plexus blocks uncover any visceral cause of pelvic pain, and ganglion impar blocks shed light on the cause of perineal (rectal, anal, vaginal) pain.

The patient's response to a nerve block helps us diagnose cervical or lumbar facet joint syndrome. Pain arising from the C2-C3 facet joints generally radiates to the occiput and that arising from C5-C6 radiates to the shoulder. We can reproduce this pain with ipsilateral rotation and extension of the cervical spine. Lumbar facet joint syndrome causes constant pain in the lumbar region that may radiate to the hips or even below the knee and can be elicited by hyperextending the spine ipsi-laterally.

Facet joint syndrome is difficult to diagnose because it arises from the same types of degenerative change that show up in x-ray images of asymptomatic joints. The diagnosis is further obfuscated because similar symptoms can arise from discopathy, nerve root impingement, and/or myofascial disease. We can differentiate facet joint syndrome by the response to radiographically guided injections of local anesthetics into the zygapophyseal joints or around the dorsal medial branches of the posterior primary rami.

Central Nerve Blocks

To determine whether a sensory nerve root is generating pain, we block central nerves by injecting local anesthetic under fluoroscopic guidance into the epidural space or onto selected dorsal roots. The use of a contrast medium helps ensure proper needle placement and spread of the local anesthetic. If the block results in pain relief, we presume that the pain generator is distal to the anesthetized site. If the block results in numbness but no pain relief, we presume the pain generator is proximal or collateral to the anesthetized site.

Differential epidural blocks can reveal whether pain is arising from the somatic nerves, the sympathetic nervous system, or the central nervous system. The first injection in a differential epidural is a placebo (saline). If this leads to pain relief, the clinicians halt the injections. If the placebo relief is long lasting, it is possible that the pain is centrally maintained or psychogenic. If the placebo provides no pain relief, we administer three injections of successively higher concentrations of local anesthetic. If the lowest concentration of anesthetic provides pain relief, we consider the pain to be sympathetically maintained. If the next level of anesthetic provides relief, we presume that the pain is somatosensory. If the pain persists, we inject the highest concentration, which usually causes a temporary loss of motor function. If this fails to provide relief, we presume the pain is centrally maintained or psychogenic.

Psychological Evaluation

Pain is, by definition, a sensory and emotional experience of actual or perceived tissue damage.1 The biologically oriented clinician may not recognize the impact of depression, anxiety, or other negative affective states on the experience of pain. The experience of pain always involves emotional dysfunction (Figure 3.5). The challenge for the pain practitioner is to differentiate between the component that is biologically driven and the component that is magnified by emotions.2 Patients with severe depression or anxiety should be evaluated to determine the impact of these comorbid psychological states on their pain. This evaluation is an important part of a medical approach to their pain and is essential before they receive interventional therapies.

Figure 3.5. Pain treatment strategy.

Patients with major depressed mood, anxiety, or other negative affective states report more pain with noxious stimuli than do controls with positive affective states. We believe that emotionally depressed patients can be appropriate candidates for interventional therapies; it is simply necessary to be especially careful when offering them therapies that carry significant risks. While it may be obvious that patients with severe pain caused by a peripheral pain generator will also experience depression or anxiety, it is less obvious that the same negative affective states actually increase the experience of pain itself. Depressed affective states can also maintain pain and cause it to take on a life of its own by dramatically amplifying what would otherwise be a relatively minor pain generator.

Frequently, a physician can determine the severity of emotional dysfunction during an initial encounter. If the patient reports anhedonia, depressed or increased appetite, a history of major depression, or difficulty sleeping, a physician should be alert to the possibility that depressed mood is an exacerbating component of the pain. When a major depression is suspected, it should be treated prior to initiating interventional techniques, directly or by referral to a competent physician who can help with this aspect of pain.

Pain Management

To reiterate: in order to determine the most appropriate therapeutic strategy, it is vital to begin by making an accurate and comprehensive pain diagnosis. The treatment of neuropathic pain might be very different from that of nociceptive pain. Likewise, the treatment of myo-fascial pain is very different from that of discogenic pain, and so forth. Frequently, the tools just discussed are sufficient to establish the diagnosis, the severity of symptoms, and the prognosis of the patient with pain. Once the diagnosis has been established, it is important to design the most appropriate strategy. This involves choosing the best strategy for the patient and selecting the appropriate patient for a given procedure. In other words, certain conditions may call for certain therapies, but for a specific patient suffering from one such condition, the usual therapies may be inappropriate. In addition, some therapies may fail in some patients and succeed in others with the same condition. Thus, most pain physicians offer a spectrum of options for patients with pain.

It is, thus, important that the physician involved in interventional pain medicine be familiar with the full spectrum of diagnostic and therapeutic care and with ways to determine appropriate patient selection for any given procedure.

Medical Therapies

Several classes of analgesics are effective in chronic pain. They should be considered as tools in a toolbox, however, not as a list of medications that must be tried prior to initiating interventional therapies.

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