Postherpetic neuralgia is the most frequent comorbidity of herpes zoster, with some residual pain (10-15%) remaining 1 month after the onset of herpes zoster. Patients with postherpetic neuralgia are not in the minority in terms of social inactivity due to pain. As people age and the incidence of herpes zoster increases, the prevention and treatment of postherpetic neuralgia has become an important issue facing our country today.
To date, there is still no decisive and long-term cure for PHN. The main goals of PHN at present are (3): (i) to relieve pain; (ii) to improve sleep; and (iii) to improve quality of life. And the main focus is on comprehensive treatment. Yan Longtao, National Pain Treatment Center, China-Japan Friendship Hospital
1.Pharmacological treatment is the main method of treating PHN at present, mainly including: antidepressants, anticonvulsants, analgesics, sedatives, NMDA receptor antagonists, lidocaine, etc.
1.1 Antidepressants Currently, tricyclic drugs are used for the standardized treatment of PHN, especially for the relief of persistent burning pain. The possible mechanism is that blocking neurons that can enhance nerve conduction has an analgesic effect, and it can also close α-adrenergic receptors and sodium channels, which act against PHN. Tricyclic drugs mainly include amitriptyline, desipramine, and nortriptyline. Amitriptyline is the most effective for herpes zoster. The optimal dose varies from case to case, starting with 25mg and 10mg for young and elderly patients respectively, and always observing whether pain relief is received, and increasing to the maximum dose before side effects appear if ineffective. The drug also has a good sleep effect. To prevent drowsiness during the day, the drug should be used daily before going to bed. Side effects of amitriptyline include sleepiness, dizziness, fatigue, dry mouth, constipation, tremor, and upright hypotension. These side effects should be explained to the patient in advance in order to continue the medication. Drowsiness and fatigue can often be reduced with continued use of the drug. Recent results based on a comparison of amitriptyline and nortriptyline suggest that they are equally effective in reducing postherpetic neuralgia, but that the latter has a lower incidence of side effects. Other tricyclic drugs such as mipramine, desipramine, doxepin, and liptirine are also effective in treating PHN, and have been used to treat PHN because selective 5-HT reuptake inhibitors have fewer side effects than tricyclic drugs, including chlorpromazine, chlorobenzotriazolone, fluoxaprofen, flutemetamol, and sertraline. Unfortunately, most published studies have failed to confirm their therapeutic effects, and perhaps only drugs that inhibit both 5-HT and norepinephrine reuptake are effective.
1.2 Anticonvulsants Anticonvulsants have been used successfully in the treatment of PHN and they seem to be the most effective drugs for the treatment of pins and needles pain in PHN. They mainly inhibit the production and afferentation of damaged primary sensory neurons and their axonal ectopic impulses through a variety of different pathways. The most commonly used drug is carbamazepine, which is effective in reducing tear-like pain and stabbing pain, but ineffective in persistent pain. Recent data suggest that gabapentin, a new drug with good analgesic effects, is now used in the treatment of PHN. It is a GABA analogue whose main mechanism is to reduce glutamatergic nerve conduction, improve GABAergic nerve conduction, and bind to voltage-dependent calcium channels to block the inward flow of calcium ions. Its main side effects are dizziness, drowsiness and ataxia, which usually disappear gradually after 2-3 weeks. Dosage: 200-600mg per dose, orally, three times a day, the maximum dose can be increased to 3200mg/d.
1.3 Analgesics ① Narcotic analgesics, represented by morphine, can selectively eliminate or relieve various pains by agonizing central opioid-like receptors. However, such drugs are significantly less effective than injurious pain in the treatment of neurogenic pain, including PHN. The available drugs are morphine (mescaline), oxycodone (oxycontin), dihydromorphone, methadone, levomorphan, fentanyl (doregine), hydroxymorphone, codeine, and the compounded formulation of Lucozade. Adverse effects include dizziness, drowsiness, excessive sweating, constricted pupils, dry mouth, nausea and vomiting, constipation, biliary colic, etc. Excessive doses or prolonged use also tend to produce respiratory depression, tolerance, euphoria and addiction. Clinical use shows that the incidence and extent of adverse reactions to opioids are related to the route of administration, and injectable drugs are prone to these adverse reactions. Therefore, non-invasive routes of administration should be chosen for the treatment of chronic pain, including PHN, such as oral, transdermal absorption, sublingual, nasal and tracheal spray inhalation, rectal suppositories, etc. Non-narcotic analgesics, including NSAIDs, tramadol, alkaloids, etc. NSAIDs are not effective in the treatment of PHN. Tramadol is a centrally acting opioid analgesic, suitable for the treatment of moderate to severe pain, and its analgesic effect is related to the effects of opioids (u agonists) and monoaminergic (inhibiting both norepinephrine and 5-HT reabsorption). Tramadol significantly reduces neurogenic pain without improving sleep abnormalities, physical weakness, psychiatric disorders, or general functional status. Its dose should be increased gradually according to the following schedule, requiring at least 48h to move from stage 1 (100mg) to stage 2 (200mg), and at least 72h to move from stage 2 to stage 3 (300mg), or from stage 3 to stage 4 (400mg) in patients under 75 years of age. For patients over 75 years of age, it takes at least 72h to move from stage 1 to stage 2 and at least 120h to move from stage 2 to stage 3.
1.4 Sedatives Phenothiazines and benzodiazepines are not effective in treating PHN by themselves, but they can be used in concert with tricyclics and analgesics because of their anxiolytic and antiemetic effects.
1.5 NMDA receptor antagonists Ketamine, as a non-competitive antagonist of NMDA receptors, has a definite analgesic effect and can be applied not only systemically but also locally, which has been adopted clinically. There is a report that long-term oral ketamine has been used for PHN analgesia for as long as 4 years and good results have been received. Some people have applied ketamine for continuous subcutaneous injection in the corresponding skin area of PHN and received good results. This method can be applied as patient-controlled pain relief. The main side effects are itching and local skin hardening at the injection site, and other side effects can include nausea, fatigue and dizziness, but it is still a feasible method (24).
1.6 Lidocaine Intravenous infusion of lidocaine for PHN, specific usage: 0.5 mg/kg, used within 2 hours, can significantly reduce pain and nociceptive hypersensitivity. Higher doses of lidocaine improve the therapeutic effect insignificantly, while systemic toxicity increases significantly. Outpatients can be given oral Meclizine, which is considered a revolutionary new drug, and it is considered, together with gabapentin, as a promising star for the future treatment of PHN.
2 .Physical therapy
2.1 Microwave therapy: Microwave has the effect of increasing local blood circulation, accelerating metabolism and reducing excitability of sensory nerves, thus reducing patients’ pain. This therapy is painless, easy to use, and the patient is highly compliant.
2.2 Laser therapy: helium-neon sublaser therapy is commonly used. Early application of low-energy laser irradiation can prevent the occurrence of PHN. The mechanism of helium-neon sublaser treatment for neuralgia is to enhance the cellular and humoral immune functions of the body, activate the mononuclear macrophage system, enhance the phagocytosis of leukocytes, and have anti-inflammatory and anti-swelling effects. The signal plays an analgesic role.
3.Local treatment
3.1 Local anesthetics Lidocaine, bupivacaine, etc. plus antipyretic analgesics (such as aspirin, etc.) are made into patches, which are used in the affected area and have received good results. The highest level of lidocaine in blood was 0.1mg/ml, indicating low systemic absorption. Its mechanism of action is to block sodium channels and reduce the sensitivity of peripheral injurious receptors and the excitability of the central nervous system. The side effect is local burning sensation.
3.2 Capsaicin Capsaicin selectively excites C-fibers causing the release of substance P. Long-term application can deplete substance P or other stored substances in nerve endings, thereby reducing or eliminating stimulus transmission from peripheral nerves to higher centers. Topical capsaicin has a transient local heat and burning sensation, and the recommended concentration varies from 0.025% to 0.10%.
3.3 Intradermal injection therapy Intradermal injection is to block sympathetic nerve endings to treat herpes zoster and herpes zoster neuralgia, which blocks the efferent impulses of sympathetic nerves, causes vasodilation, relieves local vasospasm, blocks the vicious cycle of pain, achieves rapid analgesia, and remains pain-free for a longer period of time. Intradermal injection of analgesic solution, containing 5ml of 0.5% bupivacaine, 500ug of Micropol and 10ml of 0.9% saline, totaling 16ml, is injected by dotted encirclement method or sheet encirclement method. Inject 0.2-0.4ml of analgesic solution into each spot, inject once a day for 3 consecutive days, 3 times as a course of treatment, usually 4-6 times, at least 3 times, at most 10 times.
4 .Nerve block treatment
4.1 Intrathecal injection of methylprednisolone First used by Japanese scholar Kotani: subarachnoid injection of methylprednisolone acetate 60mg and 3% lidocaine 3ml once a week for a maximum of four times, with a follow-up of two years, it was found that the patient’s pain sensation was significantly reduced and the dosage of analgesics was significantly reduced. Although there are various theoretical complications, it provides a new means of treatment for refractory cases.
4.2 Sympathetic nerve block The appropriate choice is currently considered to be a stellate ganglion block for PHN above the level of the thoracic spinal nerve distribution, and a sympathetic plexus block at the same stage for PHN in the thoracic and lumbar spinal nerve distribution. The operation of sympathetic nerve block in the thoracolumbar segment is more complicated, and care should be taken to avoid damage to the surrounding important structures.
5.Long-acting spinal nerve block and destruction
5.1 Spinal nerve root block or destruction is an important means of treating refractory PHN by using nerve root injection to degenerate the nerve root, thus achieving the purpose of long-term block. Commonly used drugs Domestic research has studied that the antitumor drug mitomycin can cause reversible degeneration of nerve roots, and methylene blue has been used in clinical practice for similar effects. Another report used the antitumor drug mitomycin, intrathecal nerve injection, according to the different sites, the dose is 10-60ml, the concentration is 1%-2%, after 21.5 months of follow-up after treatment found that in 12 cases of PHN neuralgia patients, 2 cases had better results, 6 cases were very good, the total effective rate was 66.7%, and all patients did not have complications.
5.2 Nerve pulsed radiofrequency or disruption is the most direct and effective method for the treatment of PHN. Although its indications are not clearly defined, the efficacy is definite. In our opinion, pulsed radiofrequency or destruction of sensory nerve trunks, nerve roots or ganglia can be considered if the above treatments are ineffective or if the duration of blockade is very short (less than 3 days). For treatment standardization and safety reasons, radiofrequency temperature-controlled thermocoagulation is generally used to perform nerve destruction. The device is a radiofrequency ablation therapy instrument with a controlled temperature of 45°C and a timing of 300-600 seconds. The impedance value of the nerve tissue is significantly lower than the surrounding non-nerve tissue, so the electrode position and direction can be slightly moved to lower the impedance value, which can ensure that the electrode is close to the nerve trunk or nerve root; also pay attention to the stimulation response to ensure that the needle tip is not at the motor nerve root. Then fix the electrode to implement radiofrequency treatment, so as to achieve the best treatment effect and avoid unnecessary injury.
6 .Psychological treatment Because of the long history of PHN, severe pain and extremely low quality of life, the psychological impact is very prominent, so the psychological treatment of PHN patients should be given great attention. While enhancing the treatment of pathological factors, psychological interventions should be actively carried out to interrupt the vicious cycle of pain-depression-exacerbation of pain-severe depression and to prevent suicidal tendencies. This includes placebo therapy and behavioral-cognitive therapy.
7.Other treatments Other optional applications include spinal cord electrical stimulation therapy, brain electrical stimulation therapy, and surgical therapy. Spinal cord electrical stimulation therapy is performed by percutaneous puncture under local anesthesia to determine access to the epidural cavity, then electrodes are placed in the segment involved in the lesion and electrical stimulation is given. The electrode position is adjusted according to the extent of the torso producing numbness, and when the painful area is completely covered, the electrode is then connected to a portable stimulation generator outside the body through a wire, and then the therapeutic effect of electrical stimulation on pain is observed for 1 week, and if effective, a permanent electrode is implanted. It is suitable for patients with pain that has not been treated by other means. Electrical brain stimulation methods have been reported in the literature for analgesia by stimulation of the conduction duct and periventricular gray matter, head of the caudate nucleus, amygdala and limbic system. Surgery may be considered for patients with intractable pain that is persistent and ineffective with non-surgical treatment. Surgical options include subdural spinal cord dorsal root disruption, posterior rhizotomy, open anterolateral spinal cord bundle dissection, stereotactic thalamotomy, and cingulate gyrus dissection for treatment. For PHN characterized by intractable burning pain, sympathetic trunk ganglion disruption can also be done. However, these surgical methods are highly invasive and have relatively more complications.
3 Conclusion
In conclusion, early recognition of PHN is very important, and once PHN is diagnosed and is more than 1 month old, it becomes a refractory disease, and we must set realistic rather than excessive treatment goals and gain the understanding of the patient and his family. It is very difficult to completely eliminate pain, but it is possible to combine different treatments to reduce pain to a tolerable level, and only then can the patient’s quality of life be improved.