Karl E. Misulis, MD, PhD
CHAPTER CONTENTS
◦Localization and Diagnosis of Pain Syndromes
◦Management of Neuropathic Pain
OVERVIEW
Pain can be classified into different types that have anatomic, physiologic, and symptomatic distinctions:
FEATURES: Shooting, stabbing, or burning; abnormal perception of temperature
Cause: Neuropathy from any cause, tumor infiltration, ischemia
FEATURES: Deep steady pain especially abdominal or pelvic, often with intermittent paroxysms
Cause: Distortion or distension, ischemia, infiltration
FEATURES: Deep muscular-area pain that may be crampy and movement-related
Cause: Trauma, inflammation, ischemia
FEATURES: Bone-area pain, often deep and with activity-dependent exacerbations
Cause: Trauma, arthritis, ischemia, tumor
FEATURES: Aching pain with tenderness
Cause: Ischemia from occlusive disease, inflammation
Neuropathic pain has a character that depends on the involved nerves but also on the nerve types:
•Large-fiber neuropathic pain is typically shooting or stabbing. Large-fiber pain may be associated with cutaneous sensory loss, but may be less noticeable than the sensory deficit of small-fiber neuropathy.
•Small-fiber pain is more steady, dull, aching or burning. Small-fiber neuropathic pain is often accompanied by impaired sensation of pain and temperature.
Neuropathic pain syndromes encountered in hospital practice can include:
•Peripheral neuropathy: Diabetic peripheral neuropathy is the most common cause and is usually characterized by distal burning pain and sensory loss.
•Mononeuropathy: Compression or infarction of single nerves can cause both small- and large-fiber pain in the distribution of the nerve.
•Plexopathy: Compression, section, infiltration, or inflammation of either the lumbosacral or brachial plexus can cause prominent pain and often weakness.
•Cranial nerve pain: Trigeminal neuralgia is the most common cranial nerve pain. Glossopharyngeal neuralgia is occasionally seen.
Muscular pain can be generated in the muscle fibers, associated nerves, or surrounding tissues. Some of the most common syndromes of muscle pain are:
•Muscle cramp: Often this is precipitated by a specific movement. There is often palpable muscle contraction with the cramp. Causes are many, from local muscle and innervating nerve damage to inflammation. Generalized or multifocal cramps often have a metabolic cause.
•Muscle pain with exertion: Muscle pain and cramp is common after exertion, even in athletes. This can be exacerbated by coexistent fluid or electrolyte disturbance.
Pain may bridge some of the subdivisions; for example, limb injury may result in a combination of muscular, skeletal, and neuropathic pain.
Localization and Diagnosis of Pain Syndromes
Localization and characterization of the pain are essential to diagnosis; for example, headache can have vascular or inflammatory features, but within those categories there are multiple etiologies. Some important classifications are presented in Table 10.1.
Table 10.1 Localization of pain syndromes
| Disorder | Type | Features | Etiologies |
| Headache | Vascular | Migrainous headache with throbbing of steady headache, often associated with nausea and/or photophobia | |
| Inflammatory | Steady pain, often severe, with pain with motion of the neck | Infectious meningitis, encephalitis, neoplastic meningitis | |
| Increased intracranial pressure | Holocephalic pain sometimes with visual disturbance | Tumor, infection, pseudotumor cerebri | |
| Limb pain | Bone origin | Aching pain centered in bony elements often worse with weight-bearing or change in position | Trauma, tumor |
| Muscle origin | Aching and/or cramping pain in muscular area often worse with activation of affected muscle(s) | Trauma, inflammation, | |
| Nerve origin | Lancinating and/or steady pain, usually over a defined cutaneous distribution | Neuropathy from any cause, trauma | |
| Spine pain | Bone origin | Aching or crushing pain worse with weight-bearing and torsion | Arthritis, trauma, tumor |
| Nerve origin | Local pain with radiation in the segmental distribution | Cord or cauda equina compression Nerve root compression | |
| Muscle origin | Steady paraspinal pain worse with standing and movement | Strain, trauma |
Psychology of Pain
Acute and chronic pain have distinct effects on the psychological makeup of patients.
Chronic pain: Chronic pain often produces affective disturbance, anxiety, and/or depression. Psychological response to chronic pain can be an impediment to effective pain management.
Pain without identified pathology: Limitations in diagnostic capabilities may result in misattribution of pain as being of nonorganic origin, but pain in the absence of detectable disease or pain exceeding expected symptoms raises the possibility of a psychological component to the pain.
HEADACHE
Overview
While most headache patients will present in an outpatient setting, headache remains a frequent reason for ED visits. Many times, ED physicians will manage the work-up and treatment of headache, but the neurologist may be consulted for patients with refractory headache, sudden severe headache, atypical features of headache, or those associated with abnormal neuroimaging, focal signs, or seizure.
Evaluation
Primary versus secondary headache: Primary headaches, such as migraine, cluster, and tension headache, are not related to underlying pathology. Secondary headaches are a manifestation of an underlying pathology, such as a tumor, stroke, infection, or other etiology. Features suggestive of secondary headaches should be red flags:
•Headache associated with positional changes
•New headache over the age of 50
•Abnormal neurological examination
Headache Scenarios
Select scenarios seen in the ED or hospital setting include:
First severe headache without deficit: Usually migraine in younger patients. With severe headache, imaging with computed tomography (CT) is often needed and if subarachnoid hemorrhage (SAH) or meningitis is suspected then lumbar puncture (LP) is often needed.
Recurrent severe headache without deficit: If the patient has a history of migraine, cluster, or other recurrent headache and has a typical headache, then management is the focus. Not every headache needs imaging.
Headache with cognitive change: Stroke, SAH, hydrocephalus, encephalitis, or meningitis can be causes. Evaluation starts with brain imaging. LP should be considered even in the absence of fever.
Headache with focal deficit: Stroke is of principal concern, although migraine can also produce focal deficits. Imaging must be performed.
Headache with fever: Headache can be a component of many systemic illnesses, particularly viral syndromes. LP usually has to be done to look for meningitis.
Headache with rhinorrhea: A history of head trauma associated with rhinorrhea might point toward intracranial hypotension due to a CSF leak.
New-onset headache over the age of 50: Mass lesions or temporal arteritis (giant cell arteritis) should be considered.
Headache with cough or exertion: Often a sign of primary exertional headache; however, magnetic resonance imaging (MRI) of the brain along with imaging of the vascular structures is often needed.
When to Obtain Neuroimaging
Not all patients with headache need neuroimaging. Those with episodic headache without any atypical features and with a normal neurological examination usually do not need neuroimaging.
Neuroimaging is usually indicated when the diagnosis is not known, and especially if the features suggest a serious etiology. Some of these features include:
•Sudden onset of severe headache (thunderclap)
•Headache associated with fever and/or systemic illness
•Headache associated with seizure
•Headache associated with a focal neurological examination finding
•Headache exacerbated with positional changes
•New onset headache over the age of 50
Neuroimaging modality depends on the overall clinical presentation. Those with acute neurological change should usually start with an urgent noncontrast CT of the head. Those with more subacute/chronic presentation or nondiagnostic CT will likely need MRI.
Laboratory Testing
Complete blood count (CBC) should be done in those patients with fever or possible immunocompromised state looking for any leukocytosis or anemia. Thrombocytosis can cause a hypercoagulable state, which can lead to venous occlusions and thus headache.
Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) should be obtained on every patient over the age of 50 presenting with headache. While these tests are not specific, significant elevations can point to possible temporal arteritis.
Arterial blood gases (ABG) can be obtained in those patients with respiratory issues. Hypoxia and/or hypercapnia can cause headache.
Lumbar Puncture
LP should be considered in patients who present these headache scenarios:
•Mental status changes with headache
•Signs of a systemic process, such as inflammation
•Thunderclap headache if CT is negative for SAH or other structural etiology
LP should usually be performed after neuroimaging has been performed and no mass lesions have been identified.
Differential Diagnosis
Specific conditions are discussed in Chapter 20 unless otherwise indicated.
Migraine with or without aura produces pain that can be unilateral or bilateral, regional or global. Character is often throbbing with scalp tenderness. Associated symptoms are often nausea, vomiting, photophobia, or phonophobia. Visual changes such as flashing lights, kaleidoscope effects, or heat wave sensations are often described in migraine. Migraine often has a crescendo worsening of pain over the 20- to 30-minute period. Patients usually prefer a quiet dark environment during the headache.
Cluster headache is often seen in middle-aged males. Headaches are often unilateral and associated with severe stabbing-type pain in conjunction with conjunctival injection, unilateral tearing, or rhinorrhea. In contrast to migraine patients, cluster patients are often very anxious and seek activity as an ameliorating intervention. Alcohol can often exacerbate cluster-type headaches.
Primary stabbing headache is a rare form of headache that is characterized by sudden sharp (stabbing) pain often in a consistent location, typically in the distribution of the first division of the trigeminal nerve. Although the pain is intense, the duration is often just a few seconds.
Primary exertional/sexual headache is a rare headache that will often present to the ED due to the circumstances surrounding the headache and the severe/intense nature of the headache. Exertional headache occurs most often with strenuous activity and seems to be more common in hot and/or high-altitude environments. Sexual headache often becomes most intense near or at the time of orgasm. Both headaches are described as intense throbbing headache that is often the worst the patient has ever experienced. Patients warrant neuroimaging of the brain and cerebrovasculature. Indomethacin can be effective in these headaches.
Other presentations include:
Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT): Unilateral headache is characterized by severe, short-lasting (seconds) headache that is associated with tearing and conjunctival injection. Lidocaine or phenytoin have been helpful for some patients. Select anticonvulsants are helpful. Indomethacin does not help.
Paroxysmal hemicrania: Similar presentation as SUNCT; however, headaches are longer lasting and often occur consistently on the same side of the head. Tearing, conjunctival injection, and rhinorrhea are often associated. Headaches are typically responsive to indomethacin.
Occipital neuralgia: Pain originating from the posterior portion of the head with radiation over the convexity. Typically exacerbated by palpitation of the greater and/or lesser occipital grooves. Pain is often improved with occipital nerve blocks.
Temporal arteritis: This should be considered and ruled out in any patient over 50 presenting with a headache. Headache is often unilateral, temporal, or periorbital but may be more extensive. Associated symptoms can include jaw claudication, visual changes, weight loss, malaise, ischemic optic neuropathy, and joint pains/polymyalgia rheumatica.
Pseudotumor cerebri: Most commonly seen in obese female of childbearing age. Diagnosis is made based on findings of optic nerve swelling on funduscopic examination, normal neuroimaging, and evidence of increased intracranial pressure over 25 cm H2O during LP. Symptoms include severe headaches, blurred vision, and possibly CN 6 nerve palsy.
Cerebral venous thrombosis (CVT): This should be considered in patients presenting with a possible hypercoagulable state with new-onset headache, seizure, focal weakness, or other signs of increased intracranial pressure. Pregnancy and the postpartum state predispose to CVT. (Chapter 16)
Intracranial hemorrhage: Any patient with an acute headache with mental status changes, focal weakness, and/or seizure activity should undergo immediate CT imaging of the head to rule out any intracranial hemorrhagic process. Those patients with a posterior fossa hemorrhage will often present with nausea, vomiting, and ataxia. (Chapter 16)
Cerebral ischemia/Transient ischemic attack (TIA): A small percentage of ischemic stroke patients experience headache along with a focal neurological deficit. Headache along with neck or facial pain should also raise a concern for a possible cervicocephalic arterial dissection. (Chapter 16)
Meningitis: Central nervous system infections should be considered in patients with headaches associated with mental status changes, fever, neck stiffness, cranial neuropathy, or seizure activity. (Chapter 17)
Intracranial hypotension: Patients presenting with marked positional nature to the headache and resolution in a supine position, should be evaluated for low-pressure headache, often from a CSF leak. (Chapter 26)
Acute glaucoma: Can present acutely as orbital headache, often exacerbated by eye movement, blurred vision, pupil changes. Glaucoma should be considered in patients with acute headache who are taking topiramate.1
Cerebral mass lesion: Headache from a mass lesion, either tumor or abscess, will likely present in a subacute manner. However, patients are often seen in the ED due to associated focal weakness, cranial nerve abnormality, severe worsening of the headache due to hemorrhage, and/or seizure activity. (Chapter 25)
NEUROPATHIC PAIN
Neuropathic pain rarely necessitates hospitalization, but patients may have symptoms while in the hospital for unrelated issues. Some of the painful scenarios of neuropathic pain that we are asked to consult include:
•Peripheral nerve or plexus injury
•Trigeminal neuralgia (Chapter 20)
•Glossopharyngeal neuralgia (Chapter 33)
•Herpes zoster and postherpetic neuralgia (Chapter 17)
Clinical Scenarios
Acute neural injury: Neuropathic pain from injury can be from trauma precipitating admission or hospital-related injury. Inpatients are particularly susceptible to compressive neuropathies, needle-stick injuries, plexus injuries from direct exploration, or bleeding into the region of the plexus. Bleeding into the region of the nerves or plexus can occur from extravasation of blood around the site of an arterial stick, such as for angiography.
Cancer-related neuropathic pain: Cancer patients can develop multifocal radicular pain from neoplastic meningitis. Tumors can also directly infiltrate peripheral nerves or plexus, often causing severe neuropathic pain. Bone metastases can result in collapse, indirectly producing neuropathic pain. These are discussed in Chapter 25.
Spine disease: Painful radiculopathy from spinal degenerative disease can precipitate admission to facilitate rapid diagnosis and for pain control. Radiculopathy is most likely in the lumbar region, followed by the cervical region and, more rarely, by the thoracic region.
Idiopathic: Neuropathic pain in the absence of injury can be one of the painful idiopathic cranial nerve syndromes. These are discussed in Chapter 33.
Diabetic neuropathy: The distal burning pain of diabetic neuropathy is seldom a reason for inpatient consultation, but it is important to differentiate chronic neuropathy from a superimposed developing syndrome such as acute inflammatory demyelinating polyneuropathy (AIDP) or toxic neuropathy (e.g., chemotherapy- or antibiotic-related).
Trigeminal neuralgia: Lancinating pain in the distribution of the trigeminal nerve; this condition is discussed in Chapter 20.
Postherpetic neuralgia: This neuropathic pain in the distribution of a nerve root previously affected by herpes zoster is discussed in Chapter 17.
Management of Neuropathic Pain
MANAGEMENT of neuropathic pain usually consists of medications plus physical therapy.2 Agents usually used for neuropathic pain include:
•Antiepileptic drugs (AEDs): especially gabapentin, pregabalin, carbamazepine, oxcarbazepine
•Antidepressants: especially tricyclic antidepressants (TCAs) and serotonin norepinephrine reuptake inhibitors (SNRIs)
Muscle relaxants are used for neuropathic pain even in the absence of muscle spasm or rigidity.
Analgesics used should be nonopiate if possible. If opiates are used, transition to sustained-release preparations may be appropriate.
Antidepressants are used because some have a specific effect on neuropathic pain in addition to a benefit for patients who have depression along with their pain. TCAs are often effective at doses that are subtherapeutic for depression.
Compressive Neuropathies
Compressive neuropathies in the hospital can be of almost any type, but there is a particular propensity to peroneal (fibular) and ulnar compression when patients are bed-bound. In addition, nutritional deficiencies in hospitalized patients exacerbate a number of conditions including neuropathies.
PRESENTATION is usually with decreased sensation and often pain in the affected distribution. Weakness may occur with more severe compression but might not be noted initially.
Surgical Injuries
Direct surgical injuries to peripheral nerves are uncommon. Neuropathic pain can be an associated problem, although the duration is usually limited. Medical and possibly surgical therapy may be needed, but these conditions often improve spontaneously. These are discussed in more detail in Chapter 12.
Needle and Catheter Injuries
Needle stick can directly impale a nerve or cause bleeding in the region of the nerve. Unless the patient is sedated, direct needle stick injuries of nerves are exquisitely painful from the onset. If pain begins some hours or days later, then direct stick was not the cause. Hematoma or blood extravasation produces pain that develops some minutes or hours after the event. Some of the more common needle stick neural injuries are:
•Gluteal IM injection: Sciatic nerve injury; this should be largely avoidable with attention to technique.
•Arterial line placement in the wrist: Medial or radial nerve injury
•Phlebotomy in the antecubital fossa: Medial or lateral antebrachial cutaneous nerves
•Phlebotomy at the wrist: Superficial radial nerve
SPINE PAIN
Spine pain is usually in the cervical or lumbar region, occasionally in the thoracic region. Differential diagnosis is discussed here, and specific disorders are discussed predominately in Chapter 24.
General Principles of Spine Pain
Generators of pain in the spine region are bone, paraspinal muscles, and nerves. Neural elements include spinal cord, nerve roots, and surrounding nerves. Relative contributions to the pain depend on the localization, and localization can depend on the character of pain:
•Bone pain: Poorly localized steady pain
•Muscular pain: Regional, steady, often cramping pain
•Neural pain: Usually well-localized burning, shooting, or stabbing pain
Spine Pain Syndromes
Musculoskeletal spine pain: Pathology in the vertebral body elements can be associated with tightness and cramping pain of the paraspinal muscles. Radicular symptoms and signs are absent unless accompanied by neural compression or destruction. Causes can include degenerative, traumatic, neoplastic, or inflammatory etiologies.
Cervical radiculopathy: Pain from the neck radiating into the arm, sometimes with weakness. Pain and deficit often do not have a simultaneous onset.
Lumbar radiculopathy: Pain from the low back radiating into the leg, sometimes with weakness. Pain and deficit often do not have a simultaneous onset.
Thoracic radiculopathy: Pain and sensory disturbance in a thoracic dermatome; common etiologies include herpes zoster (shingles), diabetes, thoracic disc, bony compression, and tumor. Degenerative causes are less likely than in the cervical and lumbar spine.
Conus medullaris syndrome: Compression or infiltration of the conus medullaris usually presents with back pain, leg weakness, and incontinence.
Cauda equina syndrome: Compression of the nerve roots below the conus medullaris commonly produces back and leg pain, ultimately progressing to weakness of the legs and incontinence.
Infectious meningitis: Inflammatory involvement affects the meninges and nerve roots. Chronic meningitis is especially likely to produce cranial nerve and nerve root symptoms and signs.
Neoplastic meningitis: Tumor involvement of the CSF with involvement of the meninges can cause nerve root pain and motor and/or sensory deficits.
CHRONIC PAIN SYNDROMES
Chronic pain management is beyond the scope of this book and usually is not the province of the hospital neurologist. The care given during hospitalization should be sufficient to control pain enough to make discharge possible, and the patient should be set up with a comprehensive pain management program.
MANAGEMENT of chronic pain is usually multimodal, using a combination of medications, therapy, and psychological counseling. Patients must have realistic expectations.
Sources of information on comprehensive pain management can be found in the notes to this chapter.3 , 4 Some brief guidelines include:
•Antidepressants are often used for their effect especially on neuropathic pain but also to treat the depression that accompanies chronic pain in many patients.5 Patients with depression tend to have poorer outcomes and higher disability scores. For patients with neuropathic pain, TCAs are particularly helpful for pain from small-fiber neuropathy (e.g., diabetic neuropathy).
•Analgesics are almost always used. In general, these are used in a controlled fashion, and, if narcotics are used, a contract should be established with close monitoring of use. Sustained-release formulations should be considered where appropriate.
•Antiepileptic drugs (AEDs) are often used for neuropathic pain. Large-fiber neuropathic pain is often treated with AEDs, including carbamazepine, oxcarbazepine, gabapentin, or pregabalin.
•Smoking cessation is recommended for almost all patients with nonmalignant pain. There is evidence that smoking makes pain more likely to be chronic, and smoking cessation may reduce the chronicity of pain.6 , 7
Cancer pain is treated differently than nonmalignant pain. Since many of these patients are expected to have progressive disease and have a limited life expectancy, we are more liberal about our use of analgesics. However, the non-narcotic options should be considered also since they may allow the patient to be more alert and thereby enjoy a better quality of life.
NONORGANIC PAIN
Pain is a subjective sensation, so proving that a report of pain is unreal is almost impossible. With nonorganic pain, neurologic workup usually reveals no likely source of pain that would be expected to produce the reported symptoms. Neuropsychological testing is performed on many patients with chronic pain and can help identify individuals who have psychological factors at least as a component of their pain.
ROLE OF THE HOSPITAL NEUROLOGIST
The role of the hospital neurologist in pain management depends on the capabilities and interests of the neurologist. Many pain specialists do not keep an active hospital practice, so pain management falls on the hospital attending, with assistance from neurology and anesthesiology. Our role is usually twofold: to identify the source of the pain and to advise on effective treatment.
