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Only for medical professionals to read and reference Quick Collection! Neuropathic pain (NP) is pain caused by injury or disease of the somatosensory system.
Based on the anatomical location of the injury or disease, it can be divided into peripheral neuropathic pain and central neuropathic pain
.
NP is not a single disease, but a syndrome caused by many different diseases and damages, manifested as a series of symptoms and signs, covering more than 100 clinical diseases, the more common clinical are painful diabetic peripheral neuropathy, post-herpetic zoster Neuralgia, trigeminal neuralgia, chemotherapy-induced peripheral neuropathy, postoperative chronic pain,
etc.
Table 1.
Common etiologies of NP and pathogenesis of syndrome NP The pathogenesis of NP is complex, including tissue, cellular structural changes, and functional abnormalities
.
Some current studies suggest that the possible mechanisms include changes in ion channels, peripheral sensitization, central sensitization, decreased function of the descending inhibitory system, and activation of glial cells
.
Clinical manifestations of NP After peripheral nerve damage and lesions lead to NP, the course of the disease lasts for a long time and the clinical manifestations are complex, such as sensory impairment, movement disorders, autonomic nerve dysfunction, and pain symptoms in the corresponding innervated areas.
The pain can be spontaneous, Persistent or paroxysmal pain
.
In addition, patients may experience muscle cramps, stiffness, weakness, and atrophy
.
Physical examination showed decreased muscle tone, muscle atrophy, weakening, disappearance of tendon reflexes, and paresthesias
.
Even if the original cause is removed, the injury heals or is effectively controlled, the pain still persists, which seriously affects the quality of life of the patient and is accompanied by emotional disturbance
.
The common clinical features of NP are: ①Spontaneous pain refers to the pain symptoms that appear in the body without any external stimuli, which can occur within days or weeks after nerve injury.
When a peripheral nerve is injured, the pain site Consistent with the anatomical site of the nerve trunk
.
② allodynia refers to pain caused by non-painful stimuli (such as slight feather stimulation)
.
Nerve damage patients often show hyperalgesia (or allodynia), such as light touch or stroking of the skin, bed sheets, light touch of clothing, wind, vibration, etc.
can induce pain
.
③ Hyperalgesia refers to the increased pain sensation caused by normal pain stimuli, which is caused by the decrease of pain threshold after tissue damage, and the pain degree is exaggerated
.
④Paresthesia is an unpleasant abnormal feeling that is spontaneous or induced, such as ant walking, insect crawling, itching, numbness, shooting-like feeling, pulsation-like abnormality or tightness of local tissue,
etc.
Figure 1.
Schematic diagram of the related mechanism of hyperalgesia and hyperalgesia.
There is no unified diagnostic criteria for NP.
Currently, the International Association for the Study of Pain (IASP) grading diagnostic criteria for NP is mainly used
.
The diagnostic criteria are: (1) the pain area conforms to the anatomical distribution of somatosensory nerves; (2) the medical history suggests related damage or disease in the peripheral sensory system; (3) the neurological examination confirms that at least one sign in the pain distribution area is related to the nerve damage or disease; (4) at least 1 Auxiliary examination confirmed the existence of related damage or disease of the somatosensory system
.
At the same time, if the above criteria ① to ④ are met, the diagnosis of NP can be made; if the above criteria ①, ②, ③ or ①, ②, and ④ are met, it is likely to be neuropathic pain; Auxiliary examination evidence for possible NP
.
Drug treatment of NP▌ Principles of treatment ●Drug is the main treatment method for NP at present.
It should be established on the basis of ensuring sleep and emotional stability, and carefully evaluating the nature of pain, symptoms and signs before and after treatment, and treatment response
.
●The purpose of drug therapy is not only to relieve pain, but also to treat comorbidities such as depression, anxiety, and sleep disorders
.
The selection of drugs should be based on the diagnosis and the mechanism of action of the drug, while taking into account the efficacy and safety of the drug (such as drug metabolism pathways and effects on liver and kidney function, etc.
) and the patient's clinical conditions (such as complications, contraindications, Drug interactions in concomitant medications, etc.
), and individualized treatment
.
●For the pathological characteristics of NP, it is often necessary to combine medication in clinical practice
.
●The drug withdrawal should be based on an effective and stable treatment effect and a gradual reduction method should be adopted
.
Table 2.
Recommended commonly used therapeutic drugs for different types of NP Pain relief can also improve sleep and mood
.
The absorption of the drug is less affected by food, is not bound to plasma proteins, is basically not metabolized by the liver, and has no important clinical drug interactions
.
Pregabalin is a second-generation calcium channel modulator.
Compared with gabapentin, it has enhanced affinity for α2-δ subunits, has faster titration and onset of action, has linear pharmacokinetic characteristics, and has a bioavailability of ≥90% and regardless of dose
.
Gabapentin requires slow titration to effective doses over several weeks and exhibits a nonlinear pharmacokinetic profile, with bioavailability decreasing with increasing dose
.
②Sodium channel blockers: mainly including carbamazepine and oxcarbazepine, which are the first-line drugs for the treatment of trigeminal neuralgia
.
Not recommended as first-line because of uncertain efficacy in other types of NP
.
(2) Antidepressants: ① Tricyclic antidepressants (TCAs): the most commonly used are amitriptyline and nortriptyline, which can act on multiple links in the pain transmission pathway: block a variety of ion channels, Inhibits the reuptake of serotonin and norepinephrine, mainly in the descending inhibitory pathway of pain transmission
.
Cardiotoxicity should be noted when using amitriptyline
.
②Serotonin and norepinephrine reuptake inhibitors (SNRIs): commonly used drugs include venlafaxine and duloxetine
.
These drugs selectively inhibit the reuptake of serotonin and norepinephrine, increase their concentrations in the synaptic cleft, and play a role in the descending pathway of pain transmission
.
(3) Topical medication: ① Lidocaine: Lidocaine is a voltage-gated sodium channel blocker, which reduces the abnormal discharge of peripheral nerves by blocking the abnormally expressed sodium ion channels Nav1.
8 and Nav1.
7 after nerve injury , reduces peripheral sensitization, is the first-line drug for herpes zoster-related neuralgia, and is also used to treat diabetic NP and AIDS-related NP
.
② Capsaicin: Capsaicin acts by binding to TRPV1 receptors located on Aδ fibers and C fibers.
After binding to the receptors, it causes the release of substance P, and causes short-term depolarization through the influx of sodium ions and calcium ions.
change
.
Prolonged exposure to capsaicin overstimulates and desensitizes its receptors, thereby inactivating its function
.
The analgesic effect of topical capsaicin can be explained by reversible neurodegeneration
.
High-concentration capsaicin (8%) is often used as a first-line drug for topical NP
.
(4) Tramadol: Tramadol has a dual mechanism of action, which can simultaneously act on μ opioid receptors and norepinephrine/serotonin receptors to achieve analgesic effect
.
Adverse reactions are dose-related.
Although the abuse rate is low, physical dependence can also occur, and the drug needs to be discontinued gradually
.
(5) Opioid analgesics: can be used alone or in combination with first-line drugs.
Commonly used drugs include morphine, oxycodone, and fentanyl
.
Immediate-release dosage forms are used for burst pain, and sustained-release dosage forms are used for long-term treatment of chronic pain
.
The initial dose of opioid-naïve patients should start with a small dose and be quantified individually
.
The adverse reactions of opioids may be tolerated within 1 to 2 weeks after administration, but constipation is lifelong intolerance and needs to be prevented
.
Once the cause of NP has been removed or the pain has been effectively relieved by modulating therapy, the dose should be slowly reduced until the drug is withdrawn
.
(6) Other drugs: vaccinia vaccinated rabbit skin inflammation extract, 10% ketamine patch, 0.
1% clonidine patch, 5% baclofen patch, buprenorphine transdermal patch, botulinum toxin type A, Condensine, memantine, mexiletine and some anticonvulsants (lamotrigine, sodium valproate, topiramate, etc.
) can also be used in the treatment of NP in clinical practice
.
Table 3.
Dosage, adverse reactions and precautions of commonly used drugs for NP after reading this article, how do you feel? Welcome to leave a message and share in the comment area~ References: [1] Chinese expert consensus on the diagnosis and treatment of peripheral neuropathic pain [J].
Chinese Journal of Pain Medicine, 2020, 26(05): 321-328.
[2] Neuropathic pain diagnosis and treatment expert group.
Expert consensus on diagnosis and treatment of neuropathic pain[J].
Chinese Journal of Pain Medicine,2013,19(12):705-710.
[3]Andersen Hjalte Holm,Akiyama Tasuku,Nattkemper Leigh Ann et al.
Alloknesis and hyperknesis-mechanisms,assessment methodology , and clinical implications of itch sensitization.
[J].
Pain, 2018, 159: 1185-1197.
"Heart-Leading "Shen" Gathering-2021 Annual Review of Neurology" [Preview] January 15, 2022, by "Medical Society" "The "Heart Leading "God" Gathering - Annual Inventory of Neurology in 2021" organized by the media is coming.
Professor Wang Yongjun is the chairman, and Academician Lu Lin leads the sharing.
The experts in Shennei jointly take stock of the latest research progress in 2021, covering cerebrovascular diseases.
, AD, PD, epilepsy, neuroimmunity and other 8 disease areas, transmit the strongest voice in the neurological field, create a new academic trend, and conclude the neurological research at home and abroad in 2021, looking forward to a new chapter in the research in the neurological field in 2022
.
Scan the QR code of the poster below to join the group to get the viewing link↓↓↓
Based on the anatomical location of the injury or disease, it can be divided into peripheral neuropathic pain and central neuropathic pain
.
NP is not a single disease, but a syndrome caused by many different diseases and damages, manifested as a series of symptoms and signs, covering more than 100 clinical diseases, the more common clinical are painful diabetic peripheral neuropathy, post-herpetic zoster Neuralgia, trigeminal neuralgia, chemotherapy-induced peripheral neuropathy, postoperative chronic pain,
etc.
Table 1.
Common etiologies of NP and pathogenesis of syndrome NP The pathogenesis of NP is complex, including tissue, cellular structural changes, and functional abnormalities
.
Some current studies suggest that the possible mechanisms include changes in ion channels, peripheral sensitization, central sensitization, decreased function of the descending inhibitory system, and activation of glial cells
.
Clinical manifestations of NP After peripheral nerve damage and lesions lead to NP, the course of the disease lasts for a long time and the clinical manifestations are complex, such as sensory impairment, movement disorders, autonomic nerve dysfunction, and pain symptoms in the corresponding innervated areas.
The pain can be spontaneous, Persistent or paroxysmal pain
.
In addition, patients may experience muscle cramps, stiffness, weakness, and atrophy
.
Physical examination showed decreased muscle tone, muscle atrophy, weakening, disappearance of tendon reflexes, and paresthesias
.
Even if the original cause is removed, the injury heals or is effectively controlled, the pain still persists, which seriously affects the quality of life of the patient and is accompanied by emotional disturbance
.
The common clinical features of NP are: ①Spontaneous pain refers to the pain symptoms that appear in the body without any external stimuli, which can occur within days or weeks after nerve injury.
When a peripheral nerve is injured, the pain site Consistent with the anatomical site of the nerve trunk
.
② allodynia refers to pain caused by non-painful stimuli (such as slight feather stimulation)
.
Nerve damage patients often show hyperalgesia (or allodynia), such as light touch or stroking of the skin, bed sheets, light touch of clothing, wind, vibration, etc.
can induce pain
.
③ Hyperalgesia refers to the increased pain sensation caused by normal pain stimuli, which is caused by the decrease of pain threshold after tissue damage, and the pain degree is exaggerated
.
④Paresthesia is an unpleasant abnormal feeling that is spontaneous or induced, such as ant walking, insect crawling, itching, numbness, shooting-like feeling, pulsation-like abnormality or tightness of local tissue,
etc.
Figure 1.
Schematic diagram of the related mechanism of hyperalgesia and hyperalgesia.
There is no unified diagnostic criteria for NP.
Currently, the International Association for the Study of Pain (IASP) grading diagnostic criteria for NP is mainly used
.
The diagnostic criteria are: (1) the pain area conforms to the anatomical distribution of somatosensory nerves; (2) the medical history suggests related damage or disease in the peripheral sensory system; (3) the neurological examination confirms that at least one sign in the pain distribution area is related to the nerve damage or disease; (4) at least 1 Auxiliary examination confirmed the existence of related damage or disease of the somatosensory system
.
At the same time, if the above criteria ① to ④ are met, the diagnosis of NP can be made; if the above criteria ①, ②, ③ or ①, ②, and ④ are met, it is likely to be neuropathic pain; Auxiliary examination evidence for possible NP
.
Drug treatment of NP▌ Principles of treatment ●Drug is the main treatment method for NP at present.
It should be established on the basis of ensuring sleep and emotional stability, and carefully evaluating the nature of pain, symptoms and signs before and after treatment, and treatment response
.
●The purpose of drug therapy is not only to relieve pain, but also to treat comorbidities such as depression, anxiety, and sleep disorders
.
The selection of drugs should be based on the diagnosis and the mechanism of action of the drug, while taking into account the efficacy and safety of the drug (such as drug metabolism pathways and effects on liver and kidney function, etc.
) and the patient's clinical conditions (such as complications, contraindications, Drug interactions in concomitant medications, etc.
), and individualized treatment
.
●For the pathological characteristics of NP, it is often necessary to combine medication in clinical practice
.
●The drug withdrawal should be based on an effective and stable treatment effect and a gradual reduction method should be adopted
.
Table 2.
Recommended commonly used therapeutic drugs for different types of NP Pain relief can also improve sleep and mood
.
The absorption of the drug is less affected by food, is not bound to plasma proteins, is basically not metabolized by the liver, and has no important clinical drug interactions
.
Pregabalin is a second-generation calcium channel modulator.
Compared with gabapentin, it has enhanced affinity for α2-δ subunits, has faster titration and onset of action, has linear pharmacokinetic characteristics, and has a bioavailability of ≥90% and regardless of dose
.
Gabapentin requires slow titration to effective doses over several weeks and exhibits a nonlinear pharmacokinetic profile, with bioavailability decreasing with increasing dose
.
②Sodium channel blockers: mainly including carbamazepine and oxcarbazepine, which are the first-line drugs for the treatment of trigeminal neuralgia
.
Not recommended as first-line because of uncertain efficacy in other types of NP
.
(2) Antidepressants: ① Tricyclic antidepressants (TCAs): the most commonly used are amitriptyline and nortriptyline, which can act on multiple links in the pain transmission pathway: block a variety of ion channels, Inhibits the reuptake of serotonin and norepinephrine, mainly in the descending inhibitory pathway of pain transmission
.
Cardiotoxicity should be noted when using amitriptyline
.
②Serotonin and norepinephrine reuptake inhibitors (SNRIs): commonly used drugs include venlafaxine and duloxetine
.
These drugs selectively inhibit the reuptake of serotonin and norepinephrine, increase their concentrations in the synaptic cleft, and play a role in the descending pathway of pain transmission
.
(3) Topical medication: ① Lidocaine: Lidocaine is a voltage-gated sodium channel blocker, which reduces the abnormal discharge of peripheral nerves by blocking the abnormally expressed sodium ion channels Nav1.
8 and Nav1.
7 after nerve injury , reduces peripheral sensitization, is the first-line drug for herpes zoster-related neuralgia, and is also used to treat diabetic NP and AIDS-related NP
.
② Capsaicin: Capsaicin acts by binding to TRPV1 receptors located on Aδ fibers and C fibers.
After binding to the receptors, it causes the release of substance P, and causes short-term depolarization through the influx of sodium ions and calcium ions.
change
.
Prolonged exposure to capsaicin overstimulates and desensitizes its receptors, thereby inactivating its function
.
The analgesic effect of topical capsaicin can be explained by reversible neurodegeneration
.
High-concentration capsaicin (8%) is often used as a first-line drug for topical NP
.
(4) Tramadol: Tramadol has a dual mechanism of action, which can simultaneously act on μ opioid receptors and norepinephrine/serotonin receptors to achieve analgesic effect
.
Adverse reactions are dose-related.
Although the abuse rate is low, physical dependence can also occur, and the drug needs to be discontinued gradually
.
(5) Opioid analgesics: can be used alone or in combination with first-line drugs.
Commonly used drugs include morphine, oxycodone, and fentanyl
.
Immediate-release dosage forms are used for burst pain, and sustained-release dosage forms are used for long-term treatment of chronic pain
.
The initial dose of opioid-naïve patients should start with a small dose and be quantified individually
.
The adverse reactions of opioids may be tolerated within 1 to 2 weeks after administration, but constipation is lifelong intolerance and needs to be prevented
.
Once the cause of NP has been removed or the pain has been effectively relieved by modulating therapy, the dose should be slowly reduced until the drug is withdrawn
.
(6) Other drugs: vaccinia vaccinated rabbit skin inflammation extract, 10% ketamine patch, 0.
1% clonidine patch, 5% baclofen patch, buprenorphine transdermal patch, botulinum toxin type A, Condensine, memantine, mexiletine and some anticonvulsants (lamotrigine, sodium valproate, topiramate, etc.
) can also be used in the treatment of NP in clinical practice
.
Table 3.
Dosage, adverse reactions and precautions of commonly used drugs for NP after reading this article, how do you feel? Welcome to leave a message and share in the comment area~ References: [1] Chinese expert consensus on the diagnosis and treatment of peripheral neuropathic pain [J].
Chinese Journal of Pain Medicine, 2020, 26(05): 321-328.
[2] Neuropathic pain diagnosis and treatment expert group.
Expert consensus on diagnosis and treatment of neuropathic pain[J].
Chinese Journal of Pain Medicine,2013,19(12):705-710.
[3]Andersen Hjalte Holm,Akiyama Tasuku,Nattkemper Leigh Ann et al.
Alloknesis and hyperknesis-mechanisms,assessment methodology , and clinical implications of itch sensitization.
[J].
Pain, 2018, 159: 1185-1197.
"Heart-Leading "Shen" Gathering-2021 Annual Review of Neurology" [Preview] January 15, 2022, by "Medical Society" "The "Heart Leading "God" Gathering - Annual Inventory of Neurology in 2021" organized by the media is coming.
Professor Wang Yongjun is the chairman, and Academician Lu Lin leads the sharing.
The experts in Shennei jointly take stock of the latest research progress in 2021, covering cerebrovascular diseases.
, AD, PD, epilepsy, neuroimmunity and other 8 disease areas, transmit the strongest voice in the neurological field, create a new academic trend, and conclude the neurological research at home and abroad in 2021, looking forward to a new chapter in the research in the neurological field in 2022
.
Scan the QR code of the poster below to join the group to get the viewing link↓↓↓
