Neuropathic pain is pain caused by damage or disease affecting the somatosensory nervous system. Neuropathic pain may be associated with abnormal sensations called dysesthesia or pain from normally non-painful stimuli (allodynia). It may have continuous and/or episodic (paroxysmal) components. The latter resemble stabbings or electric shocks. Common qualities include burning or coldness, “pins and needles” sensations, numbness and itching.
Neuropathic pain develops as a result of lesions or disease affecting the somatosensory nervous system either in the periphery or centrally. Examples of neuropathic pain include painful polyneuropathy, postherpetic neuralgia, trigeminal neuralgia, and post-stroke pain. Clinically, neuropathic pain is characterized by spontaneous ongoing or shooting pain and evoked amplified pain responses after noxious or non-noxious stimuli. Methods such as questionnaires for screening and assessment focus on the presence and quality of neuropathic pain. Basic research is enabling the identification of different pathophysiological mechanisms, and clinical assessment of symptoms and signs can help to determine which mechanisms are involved in specific neuropathic pain disorders. Management of neuropathic pain requires an interdisciplinary approach, centered around pharmacological treatment. A better understanding of neuropathic pain and, in particular, of the translation of pathophysiological mechanisms into sensory signs will lead to a more effective and specific mechanism-based treatment approach.[rx]
Pathophysiology of Neuropathic Pain
Neuropathic pain has been described as “pain initiated or caused by a primary lesion, dysfunction, or transitory perturbation in the peripheral or central nervous system.” Several mechanisms have been identified in the pathogenesis of neuropathic pain, but it is a lesion to afferent pathways that must be present for the syndrome to even develop. These lesions may lead to spontaneous ectopic nerve impulse generation within damaged and neighboring nociceptive fibers (C-fibers and Alpha-delta-fibers); upregulation of voltage-gated sodium channels, which contributes to changes in membrane excitability; central sensitization development as a consequence of ectopic activity; or constant release of excitatory amino acids and neuropeptides throughout the peripheral afferent fibers that leads to excitation of several receptors, such as N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic.
These varying mechanisms contribute to the development of several different types of neuropathy and result in diverse signs and symptoms. These varying mechanisms can be used to our advantage when selecting monotherapy or rational polypharmacy. Symptoms may manifest in patients as burning, pins and needles, electrical-type pain that radiates from a central locus, paresthesias, numbness, tingling, or hypersensitivity to temperature or touch. Potential causes of such neuropathies include, but are not limited to, diabetes, traumatic nerve injuries, autoimmune disorders, genetic disorders, and medications. A multitude of treatments, differing vastly in mechanisms, have been identified and proven to provide relief from these kinds of neuropathies.
Peripheral Mechanisms
Regeneration after nerve injury results in the formation of neuromas[rx]and sprouting of new nerve projections among uninjured neighboring neurons.[rx] Collateral sprouting then leads to altered sensory properties that may be realized as expanded receptive fields. Uncontrolled neuronal firing after experimental nerve injury is largely attributed to increased expression of sodium channels. This mechanism is supported by several lines of evidence, including the blockade of neuropathic pain with sodium-channel–blocking local anesthetics.[rx] Demyelination of diseased nerves may be another cause of increased neuronal excitability.[rx]
In addition to sodium channels, the expression of voltage-gated calcium channels is also increased following nerve injury.[rx] Calcium entry through voltage-gated calcium channels is necessary for the release of substance P[rx] as well as glutamate from injured peripheral nerves. Within the dorsal root ganglion, increased expression of the α-2-delta subunit of voltage-gated calcium channels correlates with onset and duration of allodynia.[rx] Clinical support of the role of this protein in neuropathic pain arises from the analgesic efficacy of α-2-delta voltage-gated calcium-channel antagonists, gabapentin and pregabalin.[rx]
Central Mechanisms
Sustained painful stimuli result in spinal sensitization,[rx] which is defined as heightened sensitivity of spinal neurons, reduced activation thresholds and enhanced responsiveness to synaptic inputs (i.e., more likely to transmit pain to the brain).[rx] This can manifest in the expansion of the affected area, increased response to painful inputs and transmission of pain following nonpainful stimuli.[rx] Central sensitization is largely mediated by the N-methyl-D-aspartate (NMDA) receptor. Although experimental NMDA-receptor blockade clearly suppresses central sensitization,[rx] analgesic efficacy of NMDA antagonists has been disappointing, likely because of the narrow therapeutic window of available agents.[rx]
Activation of descending pathways (the periaqueductal grey-rostral ventromedial medulla)[rx] has been shown to reduce pain transmission in animals[rx] and humansrx] and is thought to contribute to the analgesic effect of opioids and antidepressants. Paradoxically, this system can also facilitate pain transmission[rx] and may contribute to some chronic pain states.[rx]
Antidepressants: Pharmacology in Neuropathic Pain and Differences
The mechanism by which antidepressants relieve neuropathic pain has been identified as their ability to inhibit the reuptake of serotonin and norepinephrine (NE), with the primary mediator being NE. There are 2 classes of antidepressants whose pharmacology involve the aforementioned mechanism: tricyclic antidepressants (TCAs) and selective serotonin-NE reuptake inhibitors (SNRIs). Specific serotonin inhibitors lack quality evidence for efficacy to treat neuropathic pain.
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Available pharmacotherapy for neuropathic pain
| Drug | Mechanisms of action | NNT*(range) | Adverse effects | Precautions and contraindications |
|---|---|---|---|---|
| Tricyclic antidepressants | ||||
| Nortriptyline, desipramine, amitriptyline, clomipramine and imipramine | Monoamine reuptake inhibition, sodium channel blockade and anticholinergic effects | 3.6 (3–4.4) | Somnolence, anticholinergic effects and weight gain | • Cardiac disease, glaucoma, prostatic adenoma and seizure • High doses should be avoided in adults >65 years of age and in those with amyloidosis |
| Serotonin-noradrenaline reuptake inhibitors | ||||
| Duloxetine | Serotonin and noradrenaline reuptake inhibition | 6.4 (5.2–8.2) | Nausea, abdominal pain, and constipation | • Hepatic disorder and hypertension • Use of tramadol |
| Venlafaxine | Serotonin and noradrenaline reuptake inhibition | 6.4 (5.2–8.2) | Nausea and hypertension at high doses | • Cardiac disease and hypertension • Use of tramadol |
| Calcium channel α2δ ligands | ||||
| Gabapentin, extended-release gabapentin and enacarbil, and pregabalin | Act on the α2δ subunit of voltage-gated calcium channels, which decrease central sensitization | • 6.3 (5–8.4 for gabapentin) • 8.3 (6.2–13 for extended-release gabapentin and enacarbil) • 7.7 (6.5–9.4 for pregabalin) |
Sedation, dizziness, peripheral edema and weight gain | Reduce dose in patients with renal insufficiency |
| Topical lidocaine | ||||
| Lidocaine 5% plaster | Sodium channel blockade | Not reported | Local erythema, itching and rash | None |
| Capsaicin high-concentration patch (8%) | Transient receptor potential cation channel subfamily V member 1 agonist | 10.6 (7.4–19) | Pain, erythema, itching and rare cases of high blood pressure (initial increase in pain) | No overall impairment of sensory evaluation after repeated applications and caution should be taken in progressive neuropathy |
| Opioids | ||||
| Tramadol | μ-Receptor agonist and monoamine reuptake inhibition | 4.7 (3.6–6.7) | Nausea, vomiting, constipation, dizziness, and somnolence | History of substance abuse, suicide risk and use of the antidepressant in elderly patients |
| Morphine and oxycodone | μ-Opioid receptor agonists; oxycodone might also cause κ-opioid receptor antagonism | 4.3 (3.4–5.8) | Nausea, vomiting, constipation, dizziness, and somnolence | History of substance abuse, suicide risk, and risk of misuse in the long term |
| Neurotoxin | ||||
| Botulinum toxin A | Acetylcholine release inhibitor and neuromuscular-blocking agent; potential effects on mechanotransduction and central effects in neuropathic pain | 1.9 (1.5–2.4) | Pain at the injection site | Known hypersensitivity and infection of the painful area |
*Number needed to treat (NNT) for 50% pain relief represents the number of patients necessary to treat to obtain one responder more than the comparison treatment, typically placebo[rx].
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Summary of recommendations for pharmacological management of neuropathic pain
Duloxetine
Gabapentin
Pregabalin
TCA
Venlafaxine
Gabapentin
Pregabalin
TCA
Venlafaxine
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| EFNS [rx] | NICE [rx] | CPS [rx] | NeuPSIG [4] | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Diabetic neuropathy | Post-herpetic neuralgia | Trigeminal neuralgia | Central neuropathic pain | All neuropathic pain | Trigeminal neuralgia | All neuropathic pain | Trigeminal neuralgia | All neuropathic pain | |
| First-line therapy | Gabapentin Pregabalin TCA Lidocaine plaVenlafaxinea |
Carbamazepine Oxcarbazepine |
Gabapentin Pregabalin TCA |
Amitriptyline Duloxetine Gabapentin Pregabalin Capsaicin creamb(localized pain in patients who wish to avoid or who cannot tolerate oral treatments) |
Carbamazepine | Gabapentin Pregabalin Duloxetine Venlafaxine TCA |
Carbamazepine | Gapabentin Gabapentin ER/enacarbil Pregabalin Duloxetine Venlafaxined TCAs |
|
| Second-line therapy | Tramadol | Strong opioids Capsaicin cream |
Tramadol Strong opioids |
One of the remaining 3 oral drugs of the First-line therapy | Tramadol Strong opioids Lidocaine creamc Lidocaine patchesc |
Capsaicin patchesb Lidocaine patchesb Tramadol |
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| Third-line therapy | Strong opioids | Strong opioids | One of the remaining 3 oral drugs of the First-line therapy | Cannabinoids | Botulinum toxin type A Strong opioids |
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| Fourth-line therapy | Lamotrigine (in central post-stroke pain) Cannabinoids (in multiple sclerosis) |
Other opioids Lacosamide Lamotrigine Botulinum toxin Lidocaine cream Lidocaine patches |
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CPS Canadian Pain Society, EFNS European Federation of Neurological Societies, ER extended-release, NeuPSIGNeuropathic Pain Special Interest Group, NICE National Institute for Health and Care Excellence
aFor use in the elderly; bfor use in localized pain; cfor use in post-herpetic neuralgia; din most European countries, including Italy, venlafaxine is not approved for the indication of “neuropathic pain”, and therefore any such use should be considered off-label
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Common TCAs used in the treatment of neuropathic pain include amitriptyline, desipramine, doxepin, imipramine, nortriptyline, and trimipramine. Despite none having FDA-approved neuropathic pain management indications, this class of agents is among those preferred as first-line treatment by the IASP evidence-based guidelines for pharmacological management of neuropathic pain. Their history is quite extensive, and their role in the treatment of neuropathic pain has been highlighted by an assortment of randomized controlled trials. A meta-analysis published by Finnerup et al in 2015 found that the number needed to treat for TCAs was 3.6 (95% CI, 03.0-04.4) and the number needed to harm was 13.4 (95% CI, 9.3-24.4). A major limitation, however, is associated with the relative “sloppiness” of these medications: their tricyclic structure allows them to bind to and inhibit histaminergic-1, alpha-adrenergic, and muscarinic receptors. This haphazard capability of inhibiting numerous receptors can lead to a profusion of adverse effects (AEs) including cardiac conduction abnormalities, orthostatic hypotension, fatigue, dry mouth, constipation, sweating, or dizziness. These AEs greatly diminish the use of TCAs, making them poor choices for the vast majority of patient populations.
- Although they primarily inhibit the reuptake of serotonin and NE, SNRIs – have nontricyclic structures. These agents include venlafaxine, desvenlafaxine, duloxetine, milnacipran, and levomilnacipran. The relative selectiveness of these therapies allows them to bind only to serotonin and NE reuptake transporters while avoiding the other somatosensory receptors.
- This selectiveness remarkably reduces the risk of AEs compared with TCAs – nevertheless, SNRI is still susceptible to their own degree of adverse reactions. Common AEs include nausea, vomiting, headache, dry mouth, sweating, and an increased risk of serotonin syndrome and cardiovascular effects, such as hypertension, with minimal influence on cardiac conduction.
- The differences within this class of medications – lie in the fact that not all are FDA-approved for pain management due to their notable varied pharmacokinetic profiles. Currently, only duloxetine and milnacipran carry this indication; however, duloxetine and venlafaxine are recommended as first-line treatment for neuropathic pain by the IASP.
- As shown in the Table – the many pharmacokinetic differences exhibited between these agents may play a role in selection. Duloxetine and venlafaxine are almost entirely metabolized through CYP2D6, whereas milnacipran is almost equally eliminated through renal excretion and hepatic metabolism.
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| Drug Name (Brand) | FDA-approved Pain Management Indication | Mechanism of Inducing Neuropathic Pain | Metabolism/Elimination | Other Metabolism/Transport Effects | Common Adverse Effects |
| Tricyclic Antidepressants | |||||
| Amitriptyline (Elavil) |
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| Desipramine (Norpramin) |
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| Doxepin (Silenor) |
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| Imipramine (Tofranil) |
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| Nortriptyline (Pamelor) |
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| Trimipramine (Surmontil) |
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| Selective Serotonin-Norepinephrine Reuptake Inhibitors | |||||
| Venlafaxine (Effexor) |
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| Desvenlafaxine (Pristiq) |
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| Duloxetine (Cymbalta) |
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| Milnacipran (Savella) |
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| Levomilnacipran (Fetzima) |
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| Anticonvulsants | |||||
| Gabapentin (Neurontin) | Postherpetic neuralgia | Inhibits the alpha 2 delta subunit on voltage-gated calcium channels presynaptically, thus inhibiting the release of excitatory neurotransmitters | 100% renally excreted | None | Dizziness, somnolence, confusion, and peripheral edema. |
| Pregabalin (Lyrica) |
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| Carbamazepine (Tegretol) |
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| Oxcarbazepine (Trileptal) |
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| Topiramate (Topamax) |
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| Lamotrigine (Lamictal) |
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| Opioids | |||||
| Tramadol (Ultram) |
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| Tapentadol (Nucynta) |
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| Methadone (Dolophine) |
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| Levorphanol |
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Anticonvulsants: Pharmacology in Neuropathic Pain
- Many anticonvulsants are used to manage neuropathic pain, each varying significantly in its pharmacodynamic mechanism. Commonly used agents include gabapentin, pregabalin, carbamazepine, oxcarbazepine, topiramate, and lamotrigine. Only gabapentin, pregabalin, and carbamazepine have FDA-approved labels for the treatment of specific types of neuropathic pain. Furthermore, gabapentin and pregabalin are recommended as first-line treatment for specific neuropathies, whereas lamotrigine and carbamazepine are recommended as second-line choices by the IASP.
- As stated previously, the mechanisms associated with the anticonvulsant activity to diminish neuropathic pain are quite diverse, and truly range between different agents. Gabapentin and pregabalin primarily exert their activity by inhibiting the alpha 2 delta subunit receptors on voltage-gated calcium channels presynaptically, thereby reducing the release of stimulatory neurotransmitters. Carbamazepine and oxcarbazepine both act by inhibiting voltage-dependent sodium channels, resulting in a reduction of ectopic nerve discharges and stabilization of neural membranes. Lamotrigine also blocks the activation of voltage-sensitive sodium channels stabilizing neural membranes and inhibits the pre-synaptic release of glutamate. Topiramate has many pharmacologic properties that may help attenuate certain neuropathies, including prolonging the voltage-sensitive sodium channel inactivation state, agonizing GABAA receptors, and antagonizing NMDA receptors.
- There are also several unique pharmacokinetic properties associated with these anticonvulsants. Neither gabapentin nor pregabalin is hepatically metabolized; however, both are primarily renally excreted and thus require dosage adjustments in patients with renal insufficiency. Carbamazepine is primarily metabolized through CYP3A4 and is also a strong inducer of several enzymes, including 3A4 itself. Not only does this create the potential for many drug-drug interactions, but this auto-inducing ability increases carbamazepine’s own blood levels at or around 3 weeks from initiation or dosage adjustment. Oxcarbazepine avoids these CYP issues. Topiramate and lamotrigine are both metabolized to some degree through phase II metabolism; however, topiramate is over 70% eliminated really, consequently requiring dose adjustments in renal impairment.
Opioids: Pharmacology in Neuropathic Pain and Pharmacokinetics
- Opioids primarily relieve pain by agonizing mu-opioid receptors in both the central and peripheral nervous systems. Although this action induces analgesia to a great extent, it can also lead to significant and life-threatening AEs. These include euphoria, which may cause addiction, abuse, and misuse, and a diminished chemoreceptor response to carbon dioxide, which may result in accumulation of carbon dioxide, increasing the risk of lethal respiratory depression. Outside of this overarching ability to bind and agonize mu-receptors for their primary efficacy, certain opioids have additional actions that can specifically reduce neuropathic pain.
- Many opioids, including morphine, oxycodone, fentanyl, tramadol, tapentadol, methadone, and levorphanol, have shown efficacy in peripheral neuropathic pain; however, only tramadol, tapentadol, methadone, and levorphanol have well-established mechanisms that substantially reduce neuropathic pain. Furthermore, tapentadol is the only opioid that has FDA-labeling in regard to its treatment of neuropathies. To note, the mechanism proposed for morphine, oxycodone, and fentanyl relieving neuropathic pain is associated with their ability to inhibit voltage-gated sodium channels (similar to many anticonvulsants).
- Tramadol is a relatively weak opioid agonist, with 6000 times less binding affinity to the mu-opioid receptor than that of morphine; however, it potently inhibits the reuptake of serotonin and NE, thus providing an effect similar to that of the antidepressants used to treat neuropathic pain. Tapentadol is similar to tramadol in that it only inhibits the reuptake of NE, but differs in that it agonizes the mu-receptor to a greater extent. Methadone is an extremely potent and strong mu-agonist that also functions as a noncompetitive inhibitor of NMDA receptors and inhibits the reuptake of serotonin and NE. Levorphanol, another potent mu-receptor agonist, is a noncompetitive antagonist of NMDA receptors and an inhibitor of serotonin and NE reuptake transporters.
- Besides the differences in pharmacology, these opioids have diverse pharmacokinetic profiles. Tramadol is essentially a prodrug that requires metabolism, via CYP2D6, into its active metabolite O-desmethyl tramadol to provide adequate analgesia. Methadone is primarily metabolized through CYP3A4, 2B6, and 2C19, which makes it extremely susceptible to drug-drug interactions and elevates the risk of TdP in with a higher predisposition to poor CYP 2D6 genetic phenotypes. Both tapentadol and levorphanol are metabolized through phase 2 glucuronidation into inactive metabolites that are really excreted, making them viable options in certain patient populations. Cebranopadol and other similar opioids with unique pharmacology, including affecting NE reuptake and enkephalinase-inhibiting properties, are currently under development, all of which should prove to be superior agent opioids for treating neuropathic pain.
Treatments of Neuropathic Pain
- Neuropathic pain can be very difficult to treat with only some 40-60% of people achieving partial relief. Favored treatments are certain antidepressants (tricyclic antidepressants and serotonin-norepinephrine reuptake inhibitors), anticonvulsants (pregabalin and gabapentin), and topical lidocaine. Opioid analgesics are recognized as useful agents but are not recommended as first-line treatments.
Anticonvulsants
- Pregabalin and gabapentin may reduce pain associated with diabetic neuropathy. The anticonvulsants carbamazepine and oxcarbazepine are especially effective in trigeminal neuralgia. Gabapentin may reduce symptoms associated with neuropathic pain or fibromyalgia in some people. There is no predictor test to determine if it will be effective for a particular person. A short trial period of gabapentin therapy is recommended, to determine the effectiveness of that person. 62% of people taking gabapentin may have at least one adverse event, however, the incidence of serious adverse events was found to below.
Lamotrigine does not appear to be effective for neuropathic pain.
Antidepressants
- Dual serotonin-norepinephrine reuptake inhibitors such as duloxetine, venlafaxine, and milnacipran, as well as tricyclic antidepressants such as amitriptyline, nortriptyline, and desipramine, are considered first-line medications for this condition. While amitriptyline and desipramine have been used as first-line treatments, the quality of evidence to support their use is poor.
- Bupropion has been found to have efficacy in the treatment of neuropathic pain.
Botulinum toxin type A
- Local intradermal injection of botulinum toxin is helpful in chronic focal painful neuropathies.
Cannabinoids
- Cannabis and a number of cannabinoid receptor agonists appear to be effective for neuropathic pain.
- The predominant adverse effects are CNS depression and cardiovascular effects—which are mild and well-tolerated, but psychoactive side effects limit their use. Long-term studies are needed to assess the probability of weight gain and possible harmful psychological effects.
Dietary supplements
- A 2007 review of studies found that injected (parenteral) administration of alpha-lipoic acid (ALA) was found to reduce the various symptoms of peripheral diabetic neuropathy. While some studies on orally administered ALA had suggested a reduction in both the positive symptoms of diabetic neuropathy (dysesthesia including stabbing and burning pain) as well as neuropathic deficits (paresthesia), the meta-analysis showed “more conflicting data whether it improves sensory symptoms or just neuropathic deficits alone”.
- There is some limited evidence that ALA is also helpful in some other non-diabetic neuropathies. Benfotiamine is an oral prodrug of Vitamin B1 that has several placebo-controlled double-blind trials proving efficacy in treating neuropathy and various other diabetic comorbidities.
Neuromodulators
- Neuromodulation is a field of science, medicine, and bioengineering that encompasses both implantable and non-implantable technologies (electrical and chemical) for treatment purposes.
- Implanted devices are expensive and carry the risk of complications. Available studies have focused on conditions having a different prevalence than neuropathic pain patients in general. More research is needed to define the range of conditions that they might benefit.
Deep brain stimulation
- The best long-term results with deep brain stimulation have been reported with targets in the periventricular/periaqueductal grey matter (79%), or the periventricular/periaqueductal grey matter plus thalamus and/or internal capsule (87%). There is a significant complication rate, which increases over time.
Motor cortex stimulation
- Stimulation of the primary motor cortex through electrodes placed within the skull but outside the thick meningeal membrane (dura) has been used to treat pain. The level of stimulation is below that for motor stimulation. As compared with spinal stimulation, which is associated with noticeable tingling (paresthesia) at treatment levels, the only palpable effect is pain relief.
Spinal cord stimulators and implanted spinal pumps
- Spinal cord stimulators use electrodes placed adjacent to but outside the spinal cord. The overall complication rate is one-third, most commonly due to lead migration or breakage but advancements in the past decade have driven complication rates much lower. Lack of pain relief occasionally prompts device removal.
- Intrathecal pumps deliver medication directly to the fluid-filled (subarachnoid) space surrounding the spinal cord. Opioids alone or opioids with adjunctive medication (either a local anesthetic or clonidine) or more recently ziconotide are infused. Complications such as serious infection (meningitis), urinary retention, hormonal disturbance, and intrathecal granuloma formation have been noted with the intrathecal infusion.
- There are no randomized studies of infusion pumps. For selected patients 50% or greater pain relief is achieved in 38% to 56% at six months but declines with the passage of time. These results must be viewed skeptically since placebo effects cannot be evaluated.
NMDA antagonism
- The N-methyl-D-aspartate (NMDA) receptor seems to play a major role in neuropathic pain and in the development of opioid tolerance. Dextromethorphan is an NMDA antagonist at high doses. Experiments in both animals and humans have established that NMDA antagonists such as ketamine and dextromethorphan can alleviate neuropathic pain and reverse opioid tolerance. Unfortunately, only a few NMDA antagonists are clinically available and their use is limited by a very short half-life (ketamine), weak activity (memantine) or unacceptable side effects (dextromethorphan).
Opioids
- Opioids, while commonly used in chronic neuropathic pain, are not recommended a first or second-line treatment. In the short and long term, they are of unclear benefit. In the intermediate-term evidence of low quality supports utility.
- Several opioids, particularly levorphanol, methadone, and ketobemidone, possess NMDA antagonism in addition to their µ-opioid agonist properties. Methadone does so because it is a racemic mixture; only the l-isomer is a potent µ-opioid agonist. The d-isomer does not have opioid agonist action and acts as an NMDA antagonist; d-methadone is analgesic in experimental models of chronic pain.
- There is little evidence to indicate that one strong opioid is more effective than another. Expert opinion leans toward the use of methadone for neuropathic pain, in part because of its NMDA antagonism. It is reasonable to base the choice of the opioid on other factors. It is unclear if fentanyl gives pain relief to people with neuropathic pain.
Topical agents
- In some forms of neuropathy, especially post-herpetic neuralgia, the topical application of local anesthetics such as lidocaine is reported to provide relief. A transdermal patch containing lidocaine is available commercially in some countries.
- Repeated topical applications of capsaicin, are followed by a prolonged period of reduced skin sensibility referred to as desensitization, or nociceptor inactivation. Capsaicin not only depletes substance P but also results in a reversible degeneration of epidermal nerve fibers. Nevertheless, benefits appear modest with standard (low) strength preparations, and topical capsaicin can itself induce pain.
Surgical Interventions
In some cases, a nerve block can be used to treat.
- Carbamazepine acts by inhibiting voltage-gated sodium channels, thereby reducing the excitability of neural membranes. Carbamazepine has also been shown to potentiate gamma-aminobutyric acid (GABA) receptors made up of alpha1, beta2, and gamma2 subunits. This may be relevant to its efficacy in neuropathic pain. Carbamazepine is commonly used to help with pain attacks during the night.
- Conclusion
Neuropathic pain is connected to many diverse mechanisms and is associated with multiple disease states and medications. A wide range of therapeutic options exists for the management of neuropathic pain that differs pharmacologically and pharmacokinetically, as well as in their AE profiles. This allows providers to individualize therapy and create the most optimal pharmaceutical regimen that directly attenuates neuropathic pain.
References
