Handbook of Clinical Anesthesia
Chronic Pain Management
- Anatomy, Physiology, and Neurochemistry of Somatosensory Pain Processing (Fig. 58-1)
- Primary Afferents and Peripheral Stimulation.A variety of mechanical, thermal, and chemical stimuli may result in the sensation and perception of pain (Benzon HT, Hurley R, Deer T: Chronic pain management. In Clinical Anesthesia. Edited by Barash PG, Cullen BF, Stoelting RK, Cahalan MK, Stock MC. Philadelphia: Lippincott Williams & Wilkins, 2009, pp 1505–1531). Information about these painful or noxious stimuli is carried to higher brain centers by receptors and neurons that are distinct from those that carry innocuous somatic sensory information (Table 58-1).
- Neurochemistry of Peripheral Nerve and the Dorsal Root Ganglion.The nociceptive primary afferents (the A and C fibers) represent the principal target of pharmacologic manipulation by physicians treating pain. Glutamate receptors, as well as opioid, substance P, somatostatin, and vanilloid receptors, have been identified on the peripheral endings of these nerve fibers.
- The cell bodies of primary afferents, regardless of the structure they innervate, make up the dorsal root ganglia located just outside the spinal cord within the bony foramen.
- Primary afferent activation results in a postsynaptic excitatory event in the spinal cord. Glutamate is the primary neurotransmitter serving this function.
- Neurobiology of the Spinal Cord and Spinal Trigeminal Nucleus.Primary afferent fibers enter the gray matter of the spinal cord through the dorsal root entry zone and innervate the spinal cord.
Figure 58-1. Anatomy and physiology of somatosensory and pain processing.
- The gray matter of the spinal cord is made up of synaptic terminations of primary afferents and the second-order neurons, which form the first stage of processing and integration of sensory information.
- The gray matter of the spinal cord is divided into 10 laminae based on histologic appearance.
- The dorsal horn includes laminae I–VI and represents the primary sensory component of the spinal cord.
- The ventral horn, including laminae VII–IX and X, is involved in somatic motor and autonomic function, respectively.
- Somatic C-fiber nociceptive afferents endings primarily terminate in the laminae I and II of the same or one or two adjacent spinal segments from which they entered from the periphery. The visceral C-fiber nociceptive afferents terminate in the dorsal horn more than five segments rostrally or caudally.
- The substantia gelatinosa or lamina II also contains excitatory and inhibitory interneurons but fewer projection neurons.
- Neurobiology of Ascending Pathways
- Dorsal Column Tracts.The dorsal column contains the axons of second-order spinal cord projection
neurons in addition to the ascending axons of primary afferent neurons relaying touch, pressure, and vibratory sensation.
Table 58-1 Primary Afferent Fibers and Their Characteristics
- Spinothalamic tract(STT) neurons are the primary relay cells that provide nociceptive input from the spinal cord to supraspinal levels. The axons of STT cells cross the midline of the spinal cord through the anterior white commissure and ascend primarily in the contralateral lateral and anterolateral tracts.
- Spinobulbar Pathways.Major ascending lateral axonal projections relaying information about noxious stimuli terminate in the reticular formation of the ventrolateral medulla.
- Neurobiology of Supraspinal Structures Involved in Higher Cortical Processing.Higher cortical centers play a role in the perception of painful stimuli as well as the integration of the sensory-discriminative and affective components of the noxious stimulation.
- Transition from Acute to Persistent Nociception
- Pain sensation is unique in that it does not rapidly adapt to prolonged stimulation as do the other sensory modalities, such as fine touch (allodynia, hyperalgesia).
- Persistent C fiber (but not Aβ fiber) primary afferent activation of lamina I and V, as occurs with tissue injury and inflammation, has been shown to enhance the response to subsequent stimulation and augment the size of the receptive field of the respective dorsal horn neuron. This general phenomenon has come to be termed wind-upor central sensitization.
- Although acute noxious stimuli are transmitted to the spinal cord via Aβ and C fibers, the presence of allodynia is thought to be mediated by the activation of large-diameter Aβ fibers through what has been termed a “phenotypic” switch.
- Management of Common Pain Syndromes
- Low Back Pain: Radicular Pain Syndromes(Table 58-2)
- Low back and radicular pain secondary to a herniated vertebral disc are caused by mechanical nerve root compression and the subsequent inflammatory process.
Table 58-2 Common Causes of Low Back Pain
- The presence of a herniated disc does not necessarily result in pain.
- Patients with a herniated disc may show spontaneous regression without treatment; absence of symptoms in the presence of more abnormalities; and partial or complete resolution with treatment that includes medications, bed rest, physical therapy, traction, or epidural steroids.
- If symptomatic, the patient usually presents with low back pain and radicular symptoms that include paresthesias and numbness and weakness in the distribution of the involved nerve root. Radicular pain typically travels along a narrow band and has a sharp, shooting, and lancinating quality. Gait disturbances, loss of sensation, reduced muscle strength, and diminished reflexes involve the appropriate affected dermatomal distribution.
- Inflammation in the spinal canal secondary to a herniated disc plays an important role in the causation of back and radicular pain. A herniated nucleus pulposus results in local release of cytokines and other inflammatory mediators that cause a chemical radiculitis.
- Epidural steroid injections (ESIs) may be useful to treat some forms of low back pain because of their anti-inflammatory, local anesthetic, and antinociceptive effect. At best, ESIs may provide transient relief (no longer than 3 months) from the injections (Table 58-3).
Table 58-3 Complications of Epidural Steroid Injections
- The transient relief provided by ESIs may minimize the need for potent anti-inflammatory medications or opioids and may reduce the incidence of drug-related side effects.
- ESIs should be a component, not the sole modality, of the conservative management of radicular pain.
- It is advisable that fluoroscopy be used in ESIs to ensure insertion of the needle at the affected vertebral level and document and follow the flow of the contrast medium (and the drug).
- If there is no response to an initial injection, it can be repeated once because some patients require a second injection before they respond. If there is partial response, up to three injections can be performed.
- It appears that surgery for a herniated disc produces only short-term relief. The long-term results are comparable to those seen with conservative management. For spinal stenosis, surgery is associated with greater improvements in most outcome measures.
- Facet Syndrome
- Patients with low back pain secondary to facet problems have pain in the low back that radiate to the ipsilateral posterior thigh and usually ends at the knee. On physical examination, paraspinal tenderness and reproduction of pain occur with extension–rotation maneuvers of the back.
- The diagnosis of facet syndrome is arrived at by a combination of the patient's history, physical examination findings, and a positive response to diagnostic medial branch blocks or facet joint injections.
- Buttock Pain: Sacroiliac Joint (SIJ) Syndrome and Piriformis Syndrome
- The pain of SIJ syndrome is located in the region of the affected SIJ and medial buttock.
- Physical examination usually reveals tenderness over the sacroiliac sulcus, reduction in the joint mobility, and reproduction of the pain when the affected SIJ is stressed.
- The treatments for SIJ syndrome include physical therapy, manipulation, intra-articular steroid injections, radiofrequency denervation, and surgical fusion of the joint.
- Piriformis syndromeis another pain syndrome that originates in the buttock and affects 5% to 6% of patients referred for the treatment of back and leg pain. The pain is aggravated by hip flexion, adduction, and internal rotation. Neurologic examination findings are usually negative. There may be leg numbness when the sciatic nerve is irritated; the straight leg test result may be normal or limited.
- The diagnosis of piriformis syndrome is made on clinical grounds.
- Treatment for piriformis syndrome includes physical therapy combined with medications including muscle relaxants, anti-inflammatory drugs, and analgesics to reduce the spasm, inflammation, and pain. Local anesthetic and steroid injections into the piriformis may break the pain/muscle spasm cycle.
- Myofascial pain syndrome and fibromyalgia (MFPS)is a painful regional syndrome characterized by the presence of an active trigger point in a skeletal muscle (Table 58-4).
- The management of MFPS includes repeated applications of a cold spray over the trigger point in line with the involved muscle fibers followed by gentle massage of the trigger point and stretching of the affected muscle.
- Another treatment is local anesthetic injection or dry needling of the trigger point.
- Fibromyalgia.The American College of Rheumatology criteria for classification of fibromyalgia requires only a history of widespread pain for at least 3 months and allodynia to digital pressure at 11 or more of 18 anatomically defined tender points.
Table 58-4 Criteria for the Diagnosis of Myofascial Pain Syndrome and Fibromyalgia
III. Neuropathic Pain Syndromes
- Herpes Zoster and Postherpetic Neuralgia
- The pain of acute herpes zoster is usually moderate in severity and can be managed with analgesics. The pain usually subsides with healing of the rash. Ten percent to 15% of the patients develop postherpetic neuralgia (PHN), or pain that persists more than 3 months after resolution of the rash; the incidence increases to 30% to 50% in elderly individuals.
- The risk factors for the development of PHN include increased pain during the acute stage, greater severity of the skin lesion, older age, and the presence of a prodrome.
- The use of antiviral drugs acyclovir, famciclovir, or valacyclovir has been shown to hasten the healing of the rash, reduce the duration of viral shedding, and decrease the increase of PHN.
- Studies on the efficacy of neuraxial and peripheral nerve blocks provide conflicting results. To be effective in preventing PHN, the blocks are preferably done within 2 to 4 weeks of the onset of rash.
- The mainstay of treatment for postherpetic neuralgia is pharmacologic management that includes anticonvulsants, opioids, and antidepressants.
- Based on efficacy (numbers needed to treat), antidepressants are the first choice for neuropathic pain syndromes, followed by opioids, tramadol, and gabapentin or pregabalin.
- If quality of life, side effects, prevention of addiction, and regulatory issues are to be considered
along with pain relief, then gabapentin and pregabalin are the first drugs of choice.
Table 58-5 Symptoms of Sensorimotor Distal Polyneuropathy
- For allodynia accompanying PHN, the lidocaine patch is recommended.
- Diabetic Painful Neuropathy (DPN).Neuropathies secondary to diabetes can be classified into generalized neuropathies and focal or multifocal neuropathies. Peripheral neuropathy may be present in approximately 65% of patients with insulin-dependent diabetes mellitus (IDDM), most commonly distal symmetric polyneuropathy followed by median nerve mononeuropathy at the wrist and visceral autonomic neuropathy.
- Chronic sensorimotor distal polyneuropathy is the most common type of diabetic neuropathy (Table 58-5). The lower limbs are usually involved with loss of sensation to vibration, pressure, pain, and temperature along with absent ankle reflexes.
- The management of DPN includes tight control of the patient's blood glucose and pharmacologic therapy.
- The anticonvulsants gabapentin and pregabalin appear to be effective in the management of DPN, with the efficacy of gabapentin enhanced by the addition of controlled-release morphine.
- The tricyclic antidepressants (TCAs) are also effective in patients with DPN; the selective serotonin reuptake inhibitors are not as effective.
- Opioids and tramadol are also effective in the treatment of DPN.
- Chronic Regional Pain Syndrome (CRPS)
- There are two types of CRPS. CRPS type I was originally called reflex sympathetic dystrophy, and CRPS type II represents causalgia (Table 58-6). A discrepancy is typically seen between the severity of the symptoms and severity of the inciting injury.
The clinical features of CRPS type II are the same as in CRPS type I except there is a preceding nerve injury in CRPS II.
Table 58-6 Signs and Symptoms of Chronic Regional Pain Syndrome
- The primary treatment for CRPS includes sympathetic blocks, physical therapy, and oral medications.
- Intravenous (IV) regional anesthesia with bretylium and lidocaine or ketorolac may also be used.
- Pharmacologic therapy for CRPS includes gabapentin and memantine, a neuromuscular blocking drug.
- If the patient does not respond to the above treatments, then spinal cord stimulation can be entertained.
- Human Immunodeficiency Virus (HIV) Neuropathy.Symptomatic neuropathy occurs in 10% to 35% of patients who are seropositive for HIV, and pathologic abnormalities exist in almost all patients with end-stage AIDS.
- The sensory neuropathies associated with HIV include distal sensory polyneuropathy, the more common neuropathy related to the viral infection, and antiretroviral toxic neuropathy secondary to treatment.
- The clinical features of HIV sensory neuropathy typically include painful allodynia and hyperalgesia. The onset is gradual and most commonly involves the lower extremities.
- The treatment of HIV sensory neuropathy is symptomatic and includes optimization of the patient's metabolic and nutritional status.
- Phantom Pain.Nearly all patients with amputated extremities experience nonpainful phantom sensations,
and phantom pain, or painful sensation referred to the phantom limb, occurs in as many as 80% of amputees. The onset of pain may be immediate but commonly occurs within the first few days after amputation. Approximately 50% of patients experience a decrease of their pain with time; the other 50% report no change or an increase in pain over time.
- Phantom pain is caused by both peripheral and central factors. Peripheral mechanisms include neuromas, an increase in C-fiber activity, and sodium channel activation. Central mechanisms include abnormal firing of spinal internuncial neurons and supraspinal involvement secondary to the development of new synaptic connections in the cerebral cortex.
- The treatment of phantom limb pain includes pharmacologic and nonpharmacologic measures. Pharmacologic treatments include the use of opioids and gabapentin and the empirical use of antidepressants. The nonpharmacologic measures include transcutaneous electrical nerve stimulation, spinal cord stimulators, and biofeedback.
- Cancer Pain
Significant pain is present in up to 25% of patients with cancer who are in active treatment and in up to 90% of patients with advanced cancer.
- Cancer pain can be somatic, visceral, or neuropathic (Table 58-7)
- Management of cancer pain should be multifaceted.
- Pharmacologic therapies include opioids, antidepressants, anticonvulsants, nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, oral local anesthetics, and topical analgesics. Continuous IV
opioid infusions can be infused during the later stages of life.
Table 58-7 Causes and Characteristics of Cancer Pain
Table 58-8 Neurolytic Blocks for Visceral Pain from Cancer
- Interventional treatments include neurolytic sympathetic blocks and intrathecal opioids.
- Opioids are the mainstay of treatment for cancer pain because approximately 70% to 95% of patients are responsive when appropriate guidelines are followed. Neurolytic blocks and intrathecal opioids should be considered when pharmacologic agents are not completely effective at maximum tolerated dosages.
- Neurolytic Blocks for Visceral Pain from Cancer(Table 58-8)
- Pharmacologic Management
- Morphine is the standard for opioid therapy of cancer pain.
- Hydromorphone, a mu-receptor agonist, is three to five times more potent than morphine when given orally and five to seven times more potent when given parenterally.
- Methadone has a 60% to 95% bioavailability, a high potency, and a long duration of action. It is ideal in patients with renal failure because it does not accumulate in these patients. In 2006, the Food and Drug Administration issued an alert advisory regarding the hazards of death, opioid overdose, and cardiac dysrhythmias associated with methadone. The cardiac rhythm abnormalities include QT prolongation and torsades de pointes.
- Oxycodone is mainly a prodrug that acts primarily by being converted by to oxymorphone. The controlled-release preparation (OxyContin) has good analgesic characteristics but has become a popular drug for abuse.
- The weak opioids include codeine, hydrocodone, propoxyphene, and tramadol.
- Codeine is transformed to morphine via the enzyme cytochrome P450 2D6 (approximately 9% of white people do not have the enzyme and do not experience analgesia from codeine). Children younger than 12 years of age lack maturity of the enzyme and cannot convert the drug to morphine, so they experience the drug's side effects with minimal analgesia.
- Propoxyphene is a synthetic opioid structurally related to methadone.
- Tramadol is an opioid agonist and a monoaminergic drug.
- There is considerable public concern regarding the effect of opioids on driving performance. Patients taking stable doses of opioids can probably drive, but those who are starting to take opioids and those who have had a recent dose increase should be warned about the hazards of driving.
- Opioids are mostly used for cancer pain, with long-acting opioids supplemented by short-acting ones for breakthrough pain.
- Because of controversial issues associated with the use of opioids, such as addiction, aberrant behaviors, and regulatory issues, opioids are often second-line drugs for neuropathic pain.
- The combination of gabapentin and an opioid has been shown to result in better analgesia, fewer side effects, and the need for lower doses of each drug. Combination therapy is now commonly practiced in the treatment of patients with neuropathic pain.
- When considering the use of opioids for treatment of low back pain, it should be noted that although individual studies show the efficacy of opioids in low back pain, a meta-analysis did not show reduced pain compared with a placebo or a non-opioid control group. In addition to NSAIDs and muscle relaxants, opioids may be efficacious for short-term relief of acute low back pain, but
the long-term efficacy of opioids (≥16 weeks) is unclear. Antidepressants are preferred for treatment of chronic low back pain.
- The TCAs exert analgesic effects via multiple mechanisms (serotonergic, noradrenergic, opioidergic, and anti-inflammatory effects).
- The side effects of antidepressants include cholinergic effects such as dry mouth, sedation, and urinary retention. Accidental or intentional overdose may lead to fatal dysrhythmias. TCAs impair driving ability during the first week of treatment and during dose escalation, but driving performance returns to baseline shortly thereafter.
- Anticonvulsants block sodium channels, explaining their efficacy in patients with neuropathic pain syndromes.
- Randomized, controlled studies demonstrate the efficacy of the anticonvulsants in patients with neuropathic pain syndromes, including trigeminal neuralgia, postherpetic neuralgia, DPN, phantom limb pain, spinal cord injury pain, and Guillain-Barré syndrome.
- Gabapentin is an effective drug in patients with neuropathic pain and has few side effects.
- Lamotrigine has been shown to be effective in HIV polyneuropathy, pain from spinal cord injury, and central poststroke pain.
- Lidocaine Patch, Mexiletine, and Intravenous Lidocaine
- The 5% lidocaine patch delivers drug locally at the site of neuropathic pain generation, limiting its systemic effects and reducing its interactions with other concomitantly administered medications. Analgesia is provided through local sodium channel blockade rather than through its systemic effects.
- Mexiletine is oral lidocaine. Its efficacy is similar to IV lidocaine, although a favorable response to IV lidocaine does not necessarily mean a similar response to mexiletine.
- A meta-analysis has shown IV lidocaine to be superior to placebo and equal to morphine, gabapentin, and amitriptyline for treatment of patients with neuropathic pain.
- Interventional Procedures
Anesthesiologists who have completed a pain management fellowship are well suited to perform invasive procedures for the treatment of chronic pain. Complications from some of these invasive procedures can be serious (discitis, worsening neuropathy, paraplegia).
- The symptoms of discogenic pain are nonspecific and include nonradicular back pain that is worse in the sitting position. The pain is provoked by bending and may involve the buttock, hip, groin, and thighs. The neurologic examination results, including results for the straight leg raise, are usually normal. Magnetic resonance imaging may show a high-intensity zone on the T2 sagittal images, indicating an annular tear.
- Treatments include stabilization, exercise training, education, activity modification, and ESIs.
- Functional discography involves the insertion of a catheter and injection of a local anesthetic followed by observation of the patient's response.
- Discitis is the most feared complication of discography. The incidence of discitis is considerably decreased with prophylactic antibiotic use.
- The diagnosis of discitis includes worsening back pain the week after discography and elevated erythrocyte sedimentation rate and C-reactive protein that usually peak 3 weeks after the procedure.
- The most common causative organism in discitis is Staphylococcus aureus.
- Intradiscal electrothermal therapy (IDET)is a procedure in which a thermal resistance catheter is placed percutaneously in the posterolateral portion of the disc. Heat causes the collagen of the annulus fibrosis to contract.
- The complications of IDET may include catheter kinking or breakage, nerve root injury, nondermatomal leg pain, dural puncture, infection, bleeding, cauda equina syndrome, and spinal cord damage.
- A review comparing IDET with surgical fusion in patients with intractable discogenic low back pain showed similar improvements in both groups.
- In percutaneous disc decompression (nucleoplasty), a portion of the nucleus pulposus is removed or coagulated using radiofrequency energy.
Table 58-9 Contraindications to Percutaneous Disc Decompression
- Discography may be performed before nucleoplasty to help determine which disc is involved.
- Contraindications to Percutaneous Disc Decompression (Table 58-9)
- Vertebroplasty and kyphoplastyare percutaneous interventional modalities to treat vertebral compression fractures, a condition that is usually secondary to osteoporosis in elderly patients.
- Vertebroplasty involves the injection of polymethylmethacrylate into the affected vertebral body; kyphoplasty involves the insertion of a balloon before injection of the cement.
- Vertebroplasty is usually performed under fluoroscopic guidance, although a combination of fluoroscopy and computed tomography guidance has been described.
- Pulmonary embolism may result from leakage of cement into the paravertebral veins and bone marrow or embolism of fat particles. Neurologic complications may include radiculopathy, spinal claudication, and paraplegia.
- Kyphoplasty is associated with a greater restoration of vertebral height compared with vertebroplasty.
- Spinal Cord Stimulation
- The analgesic effect of spinal cord stimulation (SCS) involves the gate control theory.It has been hypothesized that SCS increases the input of the large nerve fibers, thus closing the “gate” at the substantia gelatinosa of the dorsal horn of the spinal cord (Table 58-10).
Table 58-10 Indications for Spinal Cord Stimulator Implantation
- Placement of the permanent stimulator is preceded by a trial period of 5 to 7 days to confirm its efficacy (Fig. 58-2).
- Complications may include nerve and spinal cord injury, infection, hematoma, and lead breakage or migration.
- Intrathecal Pumps
- Intrathecal drug delivery systems (IDDS) are a valuable option in patients in whom oral or transdermal opioids are ineffective at reasonable doses or cause unacceptable side effects.
- The main indications for IDDS is cancer pain followed by pain of spinal origin, with the majority of pumps placed in the United States for failed back surgery syndrome.
- Several factors should be considered before instituting IDDS (Table 58-11).
Table 58-11 Questions to Consider Before Intrathecal Pump Placement
Figure 58-2. Anteroposterior (A) and lateral (B) views of a spinal cord stimulator placed over the T11–T12 vertebral levels. The stimulator was placed for peripheral ischemia.
Figure 58-3. Recommendations for the management of pain by intrathecal drug delivery.
Table 58-12 Complications of Intrathecal Drug Delivery Systems
- A treatment algorithm recommends morphine and hydromorphone as acceptable first-line agents. If either morphine or hydromorphone does not produce relief or causes side effects, then one drug is switched to the other first-line drug if the patient has primary nociceptive pain, or clonidine or bupivacaine is added for patients with primary neuropathic or mixed pain syndromes.
- In 2007, a panel of experts included ziconotide as a first-line drug (Fig. 58-3).
- Fentanyl was moved to a second-line agent because the more hydrophilic agents cause intractable side effects.
- Complications of Intrathecal Drug Delivery Systems(Table 58-12)
Editors: Barash, Paul G.; Cullen, Bruce F.; Stoelting, Robert K.; Cahalan, Michael K.; Stock, M. Christine
Title: Handbook of Clinical Anesthesia, 6th Edition
Copyright ©2009 Lippincott Williams & Wilkins
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