Jacksonville Medicine, October, 1998
Duval County Medical Society, Jacksonville, FL 32204
Nerve destruction using chemicals to promote analgesia had been extensively used in the early part of the 20th century for management of pain. With the advent of newer analgesics and the development of safer techniques for pain management, its use has markedly diminished. However, recent neurodestructive techniques for pain management such as cryoablation and the use of radiofrequency lesioning resulted in a surge of interest in this method of pain relief. Unfortunately, there are no clear cut guidelines for indications, report of long term outcome, and uniformity in techniques for this type of therapeutic modality. Presently, these procedures are available as part of the management option for chronic pain and its use is usually based on the expertise of the pain specialist and the felt need of a selected group of patients. There are four methods of neurolysis:
This technique requires the administration of an agent that is capable of destroying neural structures involved in the perception of pain to promote long lasting analgesia. In the 1920's, these agents were used to treat severe pain due to cancer and other inoperable chronic conditions and whose life expectancy is relatively short (less than one year). The agents used for chemical neurolysis include phenol, ethyl alcohol, hypertonic saline, and other miscellaneous agents.
Phenol is a chemical composite containing carbolic acid, phenic acid, phenylic acid, phenyl hydroxide, hydroxybenzene, and oxybenzene. It is available as a sterile, analytical grade phenol and can be prepared to a maximum concentration of 6.7 percent solution in water. This substance is highly soluble in organic solvents such as alcohol and glycerol. The addition of small amounts of glycerol or water soluble radio-opaque contrast material may increase the concentration to 15 percent. The solution can be diluted with saline and is compatible when mixed with radiocontrast dye to allow fluoroscopic guidance during injection of the agent and to monitor spread of the solution. When mixed with glycerol, it slowly diffuses from the solution and is an advantage when injected intrathecally because it allows for limited spread and is localized in the area that needed to be destroyed. When mixed with water, it has a wider spread, causing a bigger area of nerve destruction. Aqueous solution of phenol is more potent than the glycerine solution. The choice of diluent is dependent upon the extent of neurolysis desired. The use of higher concentrations of phenol might predispose to a higher incidence of vascular injury.
Shelf life exceeds one year when the solution is refrigerated and not exposed to light. Phenol turns red on exposure to sunlight and air because of oxidation. It is metabolized in the liver by conjugation to glucuronides and oxidation to equinol compounds or to carbon dioxide and water. Excretion of metabolites is via the kidneys. Phenol has systemic side effects including central nervous system stimulation, cardiovascular depression, nausea, and vomiting. Systemic doses of more than 5 grams can cause convulsive seizures and central nervous system depression. Doses less than 100 mg are less likely to cause serious side effects.
It was first used as a neurolytic agent in 1936 by Putnam and Hampton. Phenol causes nerve destruction by inducing protein precipitation. There is loss of cellular fatty elements, separation of the myelin sheath from the axon, and axonal edema. However, phenol is not as effective as alcohol at destroying the nerve cell body and its blocking effect tends to be less profound and of shorter duration than alcohol. At a concentration of 2-3 percent in saline, phenol seems to spare motor function. The efficacy of 3 percent phenol in saline is comparable to that of 40 percent alcohol. It has an immediate local anesthetic effect due to its immediate selective effect on smaller nerve fibers. This differential blocking ability is believed to be the result of small vessel destruction that initially spares large fibers. However, the effects of the block cannot be evaluated until after 24-48 hours, to allow time for the local anesthetic effect to dissipate. The neurolytic effect may be clinically evident only after 3 to 7 days. If inadequate pain relief is obtained after two weeks, this may indicate incomplete neurolysis and requires repetition of the procedure.
The subsequent fibrosis that occurs following phenol injection makes nerve regeneration more difficult, but not impossible. Nerve regeneration can occur as long as the nerve cell body is intact, at a rate of 1 to 3 mm per day. Nerve arborization and neuroma formation can occur at the site of nerve disruption and can be a focus of a neuropathic type of pain. Phenol can be injected intrathecally and epidurally. Phenol in glycerol is hyperbaric compared to the CSF. It can be used also for paravertebral somatic block, peripheral nerve blocks, and sympathetic blocks.
Ethyl alcohol has similar destructive effect as phenol and is more efficient in destroying nerve cell bodies. Labat and Greene reported in 1933 that an injection of 33.3 percent alcohol produced satisfactory analgesia in the treatment of painful disorders. It is generally available as a 95 percent solution. Its mechanism of nerve destruction is similar to phenol. Alcohol extracts phospholipids, cholesterol and cerebroside from neural tissues and precipitates mucoprotein and lipoprotein. Although 50 to 100 percent alcohol is used as a neurolytic agent, the minimum concentration required for neurolysis has not been established. A local anesthetic is more commonly used as a diluent. Following its injection, the patient complains of severe burning pain along the nerve's distribution which may last for a minute and is subsequently replaced by a warm, numb sensation.
Alcohol is primarily used in patients with intrathecal neurolysis, sympathetic blockade, celiac plexus block and chemical hypophysectomy for patients with diffuse pain secondary to metastatic breast or prostatic malignancy. It is hypobaric to the CSF, is readily soluble in body tissues, and produces severe burning pain on injection. It spreads quite rapidly from the injection site and requires 12 to 24 hours before the effects of the injection can be assessed. Similar to phenol, if inadequate pain relief is achieved after two weeks, the block should be repeated. A concentration of 95 percent will reliably lyze sympathetic, sensory, and motor components of the nerve.Ninety to ninety-eight percent of the injected alcohol is rapidly metabolized by oxidation in the liver principally by the enzyme alcohol dehydrogenase.
The use of hypertonic saline by intrathecal injection to treat intractable pain was first reported by Hitchcock in 1967. The most commonly used solution is the 10 percent aqueous solution and is available as a pharmaceutical preparation. Its mechanism of neurolysis is not well elaborated. It causes severe pain on injection and local anesthetic is first injected before the saline solution. When administered intrathecally, hypertonic saline can cause an increase in the intracranial pressure, increase in blood pressure, heart rate and respiratory rate.
Other agents had been utilized in the past to promote neurolysis including ammonium salt solutions, chlorocresol, and distilled water. However, their neurolytic effect is unpredictable and their use is now relegated to history. Butyl aminobenzoate (Butamben) is a substance that has been reported to cause neurolysis and is under investigation.
Skin and other non-target tissue necrosis and sloughing: This is due to damage of the vascular supply to the skin, causing ischemia, and chronic trauma to denervated tissue. Necrosis of muscles, blood vessels, and other soft tissues has also been reported.
Neuritis: The reported incidence of neuritis is up to 10 percent. It is caused by partial destruction of somatic nerve and subsequent regeneration. Neuritis would occur only if the nerve cell body is not destroyed. It is less likely to occur with a subarachnoid or ganglion neurolytic block. It is clinically manifested as hyperesthesia and dysesthesia that may be worse than the original pain problem. It is one of the limiting factors in the use of chemical neurolysis.
Anesthesia Dolorosa: This is a poorly understood manifestation whereby the patient complains of distressing numbness caused by an imbalance in afferent input. It is caused by long term loss of afferent input and the resultant CNS changes.A local anesthetic block done a few hours prior to the performance of the neurolytic block seems to prevent the development of this complication. Management of this problem is pharmacotherapy with the use of tricyclic antidepressants, major antipsychotic tranquilizers, and anticonvulsants.
Prolonged motor paralysis: This can be a major complication and is greatly feared by physicians, patients and family. It occurs infrequently and is usually temporary.
Perineal and sexual dysfunction: This is another fearsome complication that can occur temporarily. About 1.4 percent and 0.2 percent of patients will have bowel or bladder dysfunction at one week and one month, respectively.
Systemic complications: These include hypotension secondary to sympathetic block and systemic toxic reactions, heart rate and rhythm disturbances, blood pressure changes, and CNS excitation and depression.
Careful patient selection is the key to a successful block. Prior to the performance of neurolysis, it should be established that the patient has a pain problem that responds to other forms of treatment. Pain should be localized and does not require multiple segmental blocks. Psychologic evaluation is also important in completely evaluating the patient before neurolysis is considered. Extensive communication with the patient is necessary and the risks and benefits of the procedure should be explained before proceeding. Understanding and acceptance of complications by the patient and the family is essential.
This modality of treatment should be used in conjunction with other therapeutic regimen including pharmacotherapy, psychologic counselling, and physical therapy. Several diagnostic local anesthetic blocks should be performed to predict a successful outcome of neurolysis. One of the blocks should be a placebo to determine placebo responders. The duration and extent of analgesia should correspond to the agent used. The purposes of the local anesthetic block are to confirm the anatomic nature of the pain and to allow the patient to experience the effects of the neurolytic block with minimal side effects. If short term pain relief is achieved and the patient is willing to accept the risks, a written informed consent must be obtained in front of a witness and the block can be performed by the specialist experienced in the planned procedure.
The success and duration of the block may vary anywhere from partial to excellent pain relief lasting from weeks to months depending upon the type of block and the skill of the physician. The most common cause of an unsuccessful block is incorrect placement of the neurolytic agent.
The different types of chemical neurolytic techniques include:
Pain relief from the destruction of nerves following exposure to extreme cold is called cryoanalgesia. Cryoablation was utilized in 1938 by Fay and Smith to promote tumor regression. The term cryoanalgesia was coined in 1976. The major advantage of this procedure is the absence of neuritis or neuroma formation, and prolonged analgesia with reversible effect unlike chemical neurolysis and to a certain extent, radiofrequency lesioning. It has no systemic side effects and produces minimal tissue damage. It is performed as an outpatient procedure. See Dr. Florete's article on cryoablation for a complete discussion of its uses and technique.
Radiofrequency lesioning is the application of electrical current to promote thermocoagulation and nerve destruction. It is used to ablate pain pathways in the trigeminal ganglion, spinal cord, dorsal root entry zone, dorsal root ganglion, sympathetic chain, facet joints, and peripheral nerves. Since it causes nerve destruction, this technique is utilized only as end of the line therapeutic modality when other measures have failed. Fluoroscopic guidance is a requirement for proper needle placement. Patients must be free from substance abuse or drug addiction, and be involved in a multidisciplinary approach to pain management including psychological counseling, behavioral management program, physical therapy, and other therapeutic modalities. The patient is also informed of the risks and benefits of the procedure and a written informed consent must be signed in front of a witness.
Frictional heat is generated by molecular movement in a field of alternating electrical current at radiofrequency. An electromagnetic field is created around an active electrode when the frequency is set above 250 kHz. The active electrode is placed at the site for lesioning and an indifferent electrode is placed to minimize passage of current through the myocardium. Heat is generated in the tissues, which conducts to the active electrode. Heat is generated as current flows through a probe with a built in thermocouple needle. The heat is not emitted from the probe itself but from the current movement which generates the heat as it passes through the tissues.
The lesion is formed once the neural temperature exceeds 45 degrees centigrade. Temperature above ninety degrees centigrade can cause boiling and tissue tearing with electrode removal. the temperature is monitored and wattage is adjusted to the desired level, which in turn determines the size of the lesion. Lesion plateaus with time. After sixty seconds at a certain temperature, lesion growth is minimal. The lesion is spheroidal and may extend several millimeters beyond the active electrode tip, but the majority of the lesion volume surrounds the axis of the active electrode. The cross sectional diameter of the lesion is generally 5-6 cm. Prior to lesioning, pain is first replicated using higher frequencies and lower voltages. Once the target tissue is localized, thermocoagulation is instituted.
See Dr. Hall's article on Radiofrequency Lesioning for a discussion of its use in managing chronic low back pain.
There are neurosurgical procedures designed to promote neurolysis. The basic principle is to interrupt sensory pathways to the brain or in the brain and brain stem. Interruption of nerve pathways results in alteration in transmission or perception of pain. Effectiveness of these techniques in promoting analgesia is variable and in some instances, wrought with side effects. These invasive treatment modalities include:
- Cranial neurectomy
- Peripheral neurectomy
Interventional pain management has taken a front seat in patient care. Old methods are modified and polished, and new techniques are being developed to produce effective prolonged analgesia for chronic pain syndromes. Neurolysis, or destruction of nerves either by the application of chemicals, heat, cold, or surgical disruption gain renewed interest and are now commonly used as one of our armamentarium in the management of previously recalcitrant chronic pain conditions. However, these techniques require specialized training, in depth knowledge of neural anatomy and understanding of chronic pain physiology. Their application should be reserved only in painful conditions where conventional conservative management fails.