Neuropathic pain treatment expert groupChongqing Southwest Hospital pain medicine Qin Xiang Wan (Reprint)Definition and classificationThe in
Neuropathic pain treatment expert group
Chongqing Southwest Hospital pain medicine Qin Xiang Wan (Reprint)
Definition and classification
The international society of pain (International Association for the Study ofPain, rASP) in 1994 (Neuropathic Pain, NP neuropathic pain) is defined as: "by the nervous system primary damage or dysfunction caused by or causing pain (Pain initiated or caused by a primary lesion or dysfunction in the nervous system). In 2008, neuropathic pain IASP special interest group (NeuPSIG) the definition updates: "caused by somatosensory system damage or disease pain" (neuropathic pain is defined as pain caused by a lesion or disease of The somatosensory system).
The following important changes have taken place in the new definition: using "damage" or "disease" instead of "dysfunction"". Using the "body feeling system" instead of the "nervous system" to make the position more clear. The name of Chinese neuropathic pain, neuropathic pain, neuropathic pain, in order to reflect the above definition and taking into account the Chinese language habits, it should be called the "unity of neuropathic pain". Neuropathic pain is divided into two types of peripheral and central, different types of pain with similar or common pathogenesis. Common types of neuropathic pain are shown in table 1.
Table 1 common types of neuropathic pain
Peripheral neuropathic pain central neuropathic pain
Post herpetic neuralgia pain after stroke
Diabetic peripheral neuropathy with pain
Glossopharyngeal neuralgia, spinal cord disease (such as spinal cord
Radicular neuropathy (cervical, thoracic or lumbosacral) cervical spondylosis, tumor pain
Pain in the spinal cord after entrapment neuropathy (such as carpal tunnel syndrome)
Posttraumatic neuropathic pain
Multiple sclerosis pain after surgery
Neuropathic pain after chemotherapy Parkinson disease
Neuropathy of phantom limb pain after radiotherapy
Stump pain pain myelitis
Neuropathy caused by tumor compression or infiltration
Alcoholic multiple neuropathy
Toxic contact neuropathy
The above table definition and classification of disease was not without controversy. For example, sympathetic related pain such as complex regional pain syndrome type I (CRPS - I), fibromyalgia (FMS), visceral pain, according to the new definition does not belong to the category of neuropathic pain, but is still in clinical reference to treat neuropathic pain.
Two, epidemiology and disease burden
NeuPSIG believes that neuropathic pain prevalence rate is about 3.3% ~ 8.2%. Another research data from Europe showed neuropathic pain in the general population prevalence rate of 8%. This data is calculated, at present in our country about 90 million of patients with neuropathic pain. Although there is no systematic research data for the quality of life of patients with neuropathic pain, but the effects of neuropathic pain on the patients' quality of life is obviously. Long term pain will not only affect the patient's sleep, work and life ability, but also increase the incidence of depression, anxiety and other affective disorders. Studies have shown that the quality of life of patients with postherpetic neuralgia is about 1/2.
There were many causes of neuropathic pain, including physical and chemical damage to the composite metabolic neuropathy. Although the patient's clinical symptoms are similar, but the causes are different. Trauma, metabolic disorder, infection, poisoning, vascular disease, nutritional disorders, tumor, nerve compression, immune and genetic and other causes can lead to nerve damage. Common causes include: diabetes, herpes zoster, spinal cord injury, stroke, multiple sclerosis, cancer, HIV infection, lumbar or cervical nerve root lesions and trauma or postoperative neurological damage, etc..
The mechanism of neuropathic pain is complex, including anatomical changes and functional damage, often caused by a variety of mechanisms. Including peripheral sensitization, central sensitization, the loss of descending inhibitory system, activation of spinal glial cells, ion channel changes, etc.. The pathological changes may involve: nerve injury, neurogenic inflammation, peripheral nerve excitability, sympathetic nervous system abnormalities and neural plasticity.
1 peripheral sensitization and central sensitization
Peripheral sensitization refers to the increased sensitivity of nociceptive neurons to afferent signals. After peripheral nerve injury, inflammatory cells and damaged cells (mast cells, lymphocytes) will release chemical substances, such as norepinephrine, bradykinin, histamine, prostaglandins, potassium, cytokines, neuropeptides and serotonin 5. These cells can sensitize the nociceptive receptors and amplify the afferent nerve signals.
Central sensitization refers to the excitability of spinal cord and spinal pain related neurons more elevated or abnormal enhancement of synaptic transmission, including spontaneous discharge activity of neurons increased, receptive field expansion, to the stimulus threshold and suprathreshold stimulus response enhancement of pathological changes and thus enlarge the pain signal transmission. The clinical manifestations of the spontaneous pain, hyperalgesia (spontaneous pain) (hyperalgesia), allodynia (allodynia, or for allodynia). Central sensitization is an important pathogenesis of neuropathic pain, maintain neuropathic pain mainly lies in the central sensitization.
2 abnormal changes of ion channels
Many ion channels may be involved in the mechanism of neuropathic pain, including calcium channel, sodium channel, chloride channel, potassium channel etc.. The current research on calcium channels show that after nerve injury, spinal cord (mainly presynaptic) expression of 2- alpha Delta Based on calcium channel, calcium ion channel abnormalities, increased calcium influx, resulting in the increase of excitatory neurotransmitter release and neuronal hyperexcitability, resulting in hyperalgesia and pain super sensitive.
Five, clinical manifestation
The clinical manifestations of neuropathic pain are complex and diverse, has its own unique properties and characteristics, including symptoms and symptoms induced by. Mainly for the long course of disease, the majority of more than 3 months. The pain is usually the same as the damaged area. Most of the original cause of pain has been eliminated or controlled but still remain pain, seriously affect the patient's work and life, often accompanied by emotional disorders. The characteristics of the pain are as follows:
1 spontaneous pain: without any trauma, injury of stimulus conditions, local or regional pain can occur.
2 pain can be caused by slight touch, such as exposure to clothing or bed sheets, or a slight change in temperature, which may cause pain and pain caused by non noxious stimulation.
3 hyperalgesia: refers to the pain caused by normal stimulation of the pain response.
4 the nature of pain: pain in patients with the same nature, to involve the kind of pain, electric shock like pain, needle like pain, tearing like pain, burning like pain, weight pain, swelling like pain and numbness like pain more.
5 abnormal feeling: can have abnormal feeling (paraesthesias), dysesthesias, itching or some other discomfort feeling.
The diagnosis of neuropathic pain mainly depends on the detailed history (including the cause, location, nature, and evoked pain alleviating factors), a comprehensive and detailed physical examination, especially the sensory system inspection and necessary auxiliary examinations, sometimes according to the patient's response to treatment.
The pain of neuropathic diagnostic criteria recommended by IASP 2008 as follows: clear nerve pain is in the range of. History suggests that peripheral or central sensory systems are associated with injury or disease. At least l auxiliary examinations showed that the pain was in accordance with the range of neuroanatomy. The at least 1 auxiliary examination confirmed the presence of related damage or disease.
Neuropathic pain is certain: 1 to meet the above 4 criteria; neuropathic pain is likely to comply with the above article: l, 2, 3 or 4 criteria; neuropathic pain may: meet the above first and 2 standards, but the lack of evidence of auxiliary examination.
Neuropathic pain pain and abnormal sensory area should be consistent with the anatomical distribution of sensory nerves, consistent with the lesion identified. For suspected neuropathic pain, neurological examination should include a detailed examination of sensory, motor and autonomic nerve function, the evaluation of sensory nerve function is very important, recommend the best quantitative analysis. Recommend the use of ID in patients with Pain self rating scale was used for screening diagnosis of neuropathic pain. DN4 and LANSS scales to identify neuropathic pain and nociceptive pain. By "in neuropathic pain associated with depression, anxiety and sleep," social function, quality of life damage, should choose the corresponding scale, such as SF-36, Nottingham (Nottingham Health Profile health, NHP) or the quality of life index (QOL) were examined. The use of the visual analogue scale (VAS) and the digital Rating Scale (NRS) was used to measure the intensity of pain. The McGill pain questionnaire (MPQ) and the simplified McGill pain questionnaire (SF-MPQ) can also be used to evaluate the intensity of pain.
Should be targeted to carry out related laboratory examinations to determine the causes, such as blood, urine, stool, cerebrospinal fluid routine and biochemistry, blood glucose, liver and kidney function tests, microbiology, immunology examination, possible poison detection etc.. A variety of examinations should be performed, such as electrophysiological examination, neuroimaging, fMRI, and skin nerve biopsy. The electrophysiological examination in the diagnosis of neuropathic pain is particularly important. Nerve conduction velocity and somatosensory evoked potential, such as conventional electrophysiological examination, are helpful to confirm, locate and quantify central and peripheral sensory conduction damage. Such as electrical stimulation of the trigeminal nerve reflex (blink reflex and masseter inhibitory reflex) is helpful in the differential diagnosis of primary trigeminal neuralgia and secondary trigeminal neuralgia (e.g., secondary to cerebellopontine angle tumor
Tumor and multiple sclerosis). When the laser evoked potential (LEP) examination especially of the sensory system damage assessment delayed LEP reliable peripheral neuropathy, primary and secondary trigeminal neuralgia, syringomyelia, multiple sclerosis, Wallenberg syndrome and cerebral infarction and other diseases in the injury. Positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) to deeply understand the mechanism of neuropathic pain may have certain significance.
Neuropathic pain is a continuous process, the disease may occur, need long-term treatment. The disease status of the current treatment is not satisfactory, not patients with neuropathic pain about half full of pain relief, which may be related to our lack of understanding of the mechanism of neuropathic pain. The treatment of neuropathic pain should be safe and effective, economic principles, the general treatment of the drug of choice for analgesia, minimally invasive treatment or neruomodulation treatment timely. The principle of treatment for neuropathic pain: early intervention, positive for treatment. Effectively relieve pain and accompanying symptoms, promote nerve repair. With appropriate rehabilitation, psychological, physical and other comprehensive treatment. The recovery of body function, reduce the recurrence rate and improve the quality of life.
(a) drug treatment
Early drug intervention, to ensure that patients sleep rest, can promote the body's self repair and may achieve the purpose of preventing disease progression, is the main treatment. Drug treatment should be based on the guarantee of sleep, stable mood, and to assess the nature of pain, the symptoms and signs before and after treatment and treatment response. The purpose of drug therapy is not only to alleviate the pain, but also to treat depression, anxiety, sleep disorders and other co morbidities. Drug withdrawal should be based on the effective and stable treatment effect and the method of reducing the dosage gradually.
In 2010, IASP and the European Academy of Neurology (European Federation of Neurological Societies alliance, EFNS) a first-line treatment of neuropathic pain in the latest version of the guidelines include calcium ion channel modulators (such as pregabalin, Gaba Martin), tricyclic antidepressants, and 5 serotonin norepinephrine reuptake inhibitors (Serotonin, Norepinephrine Reuptake Inhibitor, SNRI). In addition, local lidocaine can be used as first-line treatment of herpes zoster neuralgia (Postherpetic neuralgia, PHN), carbamazepine can be used as first-line treatment of trigeminal neuralgia. Second-line drugs including opioid analgesics and tramadol. Other drugs including other antiepileptic drugs (such as lamotrigine, topiramate), NMDA receptor antagonist and topical capsaicin etc..
Drugs for the treatment of neuropathic pain should be considered the choice of drug efficacy, safety and clinical situation of patients (e.g., complications and contraindications, combined drugs etc.). Drug selection should be individualized. For intractable neuropathic pain can be considered in combination, should be considered: the drug combination mechanism is different; the additive or synergistic effect of drugs; drug side effects are not additive. The consensus is based on the clinical evidence of different drugs.
L. first-line therapy:
(1) calcium channel modulators (Gaba Martin and Puri Balin)
Calcium channel modulators including Gaba Martin and pregabalin, is a first-line drug for neuropathic pain. The mechanism for the regulation of voltage-gated calcium channel 26 subunit IX, reduce glutamate, norepinephrine and release of substance P. In addition to reducing pain may also improve sleep and mood. The absorption of the drug is less affected by the food, not with the plasma protein binding, the basic metabolism of the liver, there is no important clinical drug interactions. The side effects were dose-dependent drowsiness and dizziness, and patients with renal insufficiency should be reduced. Gaba Martin usually starts with a dose of 300 mg per day, three times a day
Effective dose, the daily dose of 900 to 1800 mg. Puri Balin is in the development of gabapentin on the basis of a new generation of drugs and the pharmacokinetics of linear. The starting dose of the drug is 150 mg per day, divided into two times, the usual dose of 150 ~ 600 mg. In order to avoid dizziness and drowsiness, we should follow the principle of starting in the evening, using small amount, gradually increasing the amount and slowly decreasing.
Tricyclic antidepressants (TCAs)
The most commonly used for amitriptyline. Can play a role in the pain conduction pathway of multiple links: blocking a variety of ion channels, inhibit 5. The reuptake of serotonin and norepinephrine, which plays a major role in the downstream pathway of the pain pathway. Is currently the first-line drug in the treatment of neuropathic pain. In the first dose should be given before bedtime, each 12.5 to 25 mg, according to the patient's reaction gradually increase the dose, maximum daily dose of 150 mg. The use of amitriptyline should pay attention to the cardiac toxicity, sinus tachycardia, orthostatic hypotension, ventricular ectopic beats, increase myocardial ischemia and sudden cardiac death. TCAs should be avoided in patients with ischemic heart disease or sudden cardiac death. In addition, the drug may cause or exacerbate cognitive impairment and gait abnormalities.
Serotonin reuptake inhibitor (5-), norepinephrine (SNRIs)
Commonly used drugs were venlafaxine and duloxetine etc.. The drugs selectively inhibited the reuptake of serotonin and norepinephrine, and increased the concentration of two in the synaptic gap, and played an important role in the pathway of the pain pathway. The effective dose of venlafaxine for daily 150 ~ 225 mg, each at a time. The initial dose of duloxetine was 30 mg per day, adjusted to a daily dose of mg at a dose of 60 a day, once or twice. The common adverse reactions are nausea, dry mouth, sweating, fatigue, anxiety, tremor, etc..
(3) local lidocaine
Often used as first-line therapy for herpes zoster associated neuralgia. There are common formulations of lidocaine gel agent and patch. Side effects include skin erythema or rash.
C Masi Bing (4), oxcarbazepine
C Masi Bing and oxcarbazepine is sodium channel blockers, can be used as first-line treatment of trigeminal neuralgia. C Masi Bing initial dose: 200 to 400 mg per day, the effective dose for each eye of 200 ~ 1200 mg. Side effects were more common, including sedation, dizziness, abnormal gait, elevated liver enzymes, hyponatremia, and bone marrow suppression. There is a risk of exfoliative dermatitis
Life-threatening Stenens--Johnson syndrome and septic shock. Oxcarbazepine effective dose of ~ 1800 mg per 600. Drug dosage should be increased according to patient's clinical response. Oxcarbazepine can produce liver enzyme induction, skin allergic reaction than C Masi Bing and C Masi Bing are rare, 25% ~ 30% cross allergy, can also lead to hyponatremia.
2 second-line drugs
Tramadol has a dual mechanism, can also act on opioid receptor and norepinephrine / 5- serotonin receptor to achieve analgesic effect. The side effects were related to the dose, and the common side effects were nausea, vomiting, dizziness and so on. The starting dose was 25 to 50mg per day, daily for 1 to 2 times, the maximum amount of daily 400mg. Care should be taken not to use 5 of the serotonergic drugs (including SNRIs) in order to avoid the risk of the 5 serotonin syndrome. The drug abuse rate is low, but also physical dependence, the need for gradual withdrawal.
(2) opioid analgesics
Often used as second-line drugs can be used alone, or with a combination of drugs, drugs commonly used morphine, oxycodone and fentanyl. Sustained release dosage form for the treatment of chronic pain in chronic pain. The initial dose of patients who had not used opioids should start at a small dose and the individual should be quantified. The side effects of opioids are nausea and vomiting, excessive sedation, respiratory depression, after 1 ~ 2 weeks may occur within the tolerance, but life does not need to be tolerant of constipation, prevention, long-term use may lead to dependence. Once the cause of the removal or treatment of neuropathic pain control effectively relieve pain, reduce the dosage of medication should slow to remove.
3 other drugs
In addition to the drugs, some drugs have been widely used in clinical practice, including vaccinia vaccination rabbit skin inflammation, extract of bulleyaconitine A, topical capsaicin, intravenous lidocaine, Mei Jingang, mexiletine and some antiepileptic drugs (sodium valproate, lamotrigine, topiramate etc.).
(two) neural regulation technique
Neural control technology mainly includes electric (magnetic) stimulation technique and intrathecal drug injection technology is lost, the neuropathic pain treatment recommendation technology.
1 nerve electrical stimulation
The route of action and the purpose of treatment are different. Are commonly used in clinical Han's acupoint nerve stimulation (HANS), transcutaneous electrical nerve stimulation (TENS), spinal cord stimulation (SCS), transcranial magnetic stimulation (rTMS) method. HANS is to stimulate the brain and spinal cord opioid peptides and other neurotransmitters through the nerve stimulation of acupoints, and play a role in analgesia. The effect of different stimulation frequency produced by different, such as low frequency (2Hz) stimulation can cause enkephalin and the release of endorphins, 100 Hz (100 Hz) electrical stimulation can induce the release of dynorphin, and 2 Hz and 100Hz alternate dilatational wave appeared (D-D frequency), the enkephalin, endorphins these 3 kinds of peptide and dynorphin opioid peptides also released, in order to achieve maximum analgesic effect, fully play a role in treatment. In addition, low frequency (2 Hz) electrical stimulation can also cause long-term inhibition (L1D) in the spinal dorsal horn, which can prevent the damage information from being uploaded. However, high frequency stimulation can cause long-term potentiation (LTP) of the dorsal horn neurons.
Transcutaneous electrical nerve stimulation (TENS) is a kind of electrical stimulation of different nerves related to the conduction of pain information, which can reduce the transmission and reception of pain information, thus relieving pain. The possible mechanism of TENS is as follows: weak high frequency electric stimulation stimulates the nerve fiber, activates the pain gate control system, closes the gate, and prevents the pain from transmitting to the central nervous system. For the adjuvant treatment of neuropathic pain after peripheral nerve injury in clinical.
Deep nerve stimulation can be divided into motor cortex electrical stimulation, deep brain stimulation, spinal cord stimulation. Spinal cord stimulation is widely used in the field of nerve electrical stimulation. The failure of spinal cord stimulation is mainly applied to the standard drug therapy is invalid or cannot tolerate the drug back surgery syndrome, complex regional pain syndrome, adhesive arachnoiditis, neuropathic pain, pain, and not immediately around the stump of surgery such as angina pectoris.
2 intrathecal drug infusion therapy
Intrathecal drug infusion therapy is buried by infusion pump in drug patients, the drug pump infusion to patients with subarachnoid, acting on spinal cord or corresponding central sites, blocking pain signals to the CNS, which can not reach the cortical pain signals, so as to achieve the purpose of controlling the pain. The common drugs intrathecal pump preparation including opioids, local anesthetics, calcium channel blockers, alpha -2 receptor agonists and NMOA receptor antagonists, the clinical application of morphine most widely, is also regarded as the first-line drug. Pre test dose of morphine used in the continuous injection of (dose titration), the usual first dose from parenteral doses of 1%, according to the analgesic effect and the general condition of the patients gradually adjusted, in order to achieve the best analgesic effect and minimal adverse reaction.
(three) minimally invasive treatment
The main purpose of minimally invasive treatment is to remove the causes of sensory nerve injury, increase the blood flow, and promote nerve recovery. Mainly including nerve block, radio frequency treatment and nerve damage and other technology, minimally invasive treatment is also a new trauma to the patient, so we need to weigh the pros and cons of patients for. The principle of minimally invasive treatment of modern medicine is the first clear reason of neuropathic pain sensory nerve injury, the minimally invasive treatment. Efforts to promote the process of sensory nerve recovery, as far as possible to avoid nerve damage treatment.
1 nerve block
Nerve block is commonly used in treatment of neuropathic pain, nerve block drug selection must consider the following issues. The mechanism of action and therapeutic purpose of drugs; adverse reactions; the advantages and disadvantages of combined use of drugs. At present, it is widely recognized that the treatment of nerve block is mainly composed of local anesthetics, glucocorticoids, opioids, nerve damage drugs and so on.
Nerve block should do adequate assessment of the patient's condition, grasp the nerve block the indications, mechanism of drug block anatomical structure, familiar with the site of block, puncture and operation technical specification, the effect of nerve block and accurate assessment, and to evaluate the possible complications and prevention.
2 radiofrequency therapy
Radio frequency therapy, including radiofrequency thermocoagulation and pulsed radio frequency, is the most characteristic of the nerve can be close to the nature of the nerve, such as motor or sensory nerve, and can evaluate the distance between the tip and the nerve. It was initially thought that the temperature in the process of radiofrequency induced nerve fiber degeneration, thereby blocking the conduction of pain. However, only a short period of time after the radiofrequency ablation of the corresponding skin sensation, pain relief time is often longer than its apparent persistence. Therefore, temperature may not be the only mechanism to change the conduction of pain. Radio frequency can be used to determine the damaged area by stimulation and impedance monitoring, and can adjust the range and degree of damage by adjusting the radio frequency parameters (temperature and time), avoiding the side effects such as carbonization and adhesion. Pulsed radiofrequency (RF) is a kind of neuromodulation therapy, the mechanism of which is to stimulate the pain of the signal transduction pathway and induce the inhibition of pain. Pulsed RF current of 2 Hz and 20 ms, the temperature is lower than 42 DEG C, the nerve fiber anatomy no damage, and have certain effect to relieve neuropathic pain.
3 nerve damage
Destructive treatment including chemical damage, physical (RF, freezing, radiation damage and damage) surgical treatment, is irreversible, it may have dominated the numbness and muscle weakness of complications, indications should be strictly controlled, and obtain informed consent of patients.