Varicella-zoster virus (VZV) is a herpesvirus with minimal double helix DNA that has a short growth cycle, spreads rapidly in a variety of cells and tissues, and causes cell-to-cell infection. ).
VZV is airborne, enters the body from the respiratory tract, spreads rapidly through the lymphatic tissues of the pharynx to the T lymphocytes of the circulatory system, and then invades the dorsal root ganglion or trigeminal ganglion along the sensory nerves of the injured skin and the bloodstream, where it is latent in the infected sensory neurons. It remains with the host for life.
The acute phase of HZ lasts for 3 weeks and is accompanied by severe spontaneous and touch-induced pain (Allodynia), from which most patients recover completely within a few months. However, 9% to 34% of patients with HZ develop persistent postherpetic neuralgia (PHN) after the skin injury has healed.
Decreased body resistance, malignancy, chronic kidney or lung disease, cellular immune dysregulation and aging are the main factors that induce activation of latent VZV. The activated virus first replicates in the cytosol of sensory neurons and then spreads along sensory nerves to the skin, causing herpes in the corresponding dermatomes innervated by sensory neurons. Depending on the infected peripheral sensory neuron fibers, herpes occurs in different parts of the body, with the highest incidence of 51.2% in the thoracic segment, followed by 18.9%, 18.3% and 11.6% in the cephalic, lumbosacral and cervical segments, respectively.
The main risk factors for the transformation of acute HZ into PHN include aging, acute pain, severe herpes and herpes of the eye, etc. PHN belongs to the category of neuropathic pain, and according to US statistics, the incidence of PHN is the highest among all types of neuropathic pain, second only to low back pain and diabetic neuralgia, with 500,000 cases per year. The incidence and duration of HZ are proportional to age: 3-4% for 30-49 years old, 29% for 70-79 years old, and 80 years old.
The pathology of HZ and PHN has been studied for more than 100 years. 1860 von Barensprung first examined the effect of herpes on sensory ganglia, and in 1990 Henry Head, a pioneer in sensory physiology, and his colleague A.W. Campbel began to systematically study the etiology of herpes zoster. The author searched PubMed for the term “Herpes Zoster” and as of November 2013, 13528 articles have been published, the majority of which are related to clinical treatment and only a few to mechanistic studies. Since the cause of HZ pain is still unclear, there are no ideal drugs and means of treatment.
I. Mechanistic studies
Due to the race specificity of human VZV, there has been no animal model of HZ for a long time in the past, which seriously hindered the study of the mechanism. It was not until the end of the 20th century that HZ models in rats and mice were successfully established, providing conditions for the study of HZ and PHN mechanisms. The process of herpes zoster production includes viral activation, expression of pro-cytolytic genes, viral spread within sensory ganglia and replication in adjacent cells, which eventually leads to tissue damage (local hemorrhage, demyelination, axonal degeneration, necrosis of sensory nerve fibers and supporting cells, etc.), triggering sensitization of peripheral and central pain-related neurons and causing intense pain.
1. Clinical observations and pathological examinations have provided important insights into the neural mechanisms of pain production through clinical manifestations, case studies and experimental studies of patients with HZ and PHN. According to a large amount of clinical data, the factors that produce PHN can be summarized as follows.
(i) Most drugs that impair cellular immunity (e.g., transient oral hormones), decreased immune function due to disease, and stress (e.g., death of a spouse or unemployment) can induce the resurgence of varicella-zoster virus.
(ii) Impairment of heat-sensitive afferent fibers in the infected skin of patients with acute HZ correlates with later production of PHN;
(iii) Diabetic patients are two times more likely to produce PHN than the non-diabetic population; there is a strong age dependence in the incidence of HZ.
(1) Pathological changes: In addition to activation of VZV in sensory neurons of the dorsal root ganglion or trigeminal ganglion, there is also replication of the virus in infected skin, blood mononuclear cells, and cerebrospinal fluid. Pathological changes are manifested by acute hemorrhagic necrosis and loss of dorsal root ganglion neurons, expression of eosinophilic inclusion bodies by satellite cells, thinning and localized demyelination of peripheral nerve fiber myelin and complete conversion to collagen. The damage to peripheral sensory nerves was bilateral and asymmetric, and motor nerves in the corresponding spinal cord segments were also damaged. In addition, autopsy of the HZ patient showed that damage occurred not only to the peripheral nerves but also to the ipsilateral spinal cord in several spinal cord segments, with significant wrinkling of the dorsal horn.
(i) Almost all nerves innervating the epidermis expressed the injury receptor marker, calcitonin gene-related peptide (CGRP).
(ii) The thick myelinated nerve fibers innervating the hair follicles and dermal papillae and the finer myelinated fibers innervating the epidermis without passing through the dermal papillae were significantly reduced, while the unmyelinated fibers expressing the capsaicin receptor TRPV1 were increased.
(iii) Markers of myelinated thick fibers innervating the dermal papillae were negative for NF, indicating the absence of thick fibers. However, there are many fine fibers in the epidermis that are positive for the coarse fiber marker NF when compared to normal skin. This abnormal innervation may be due to damage to large and small fibers, causing remnant neurons with long shoots of unmyelinated axons to re-innervate their target tissue.
These findings were confirmed in the intercostal neuropathology of patients with PHN, where there was a sustained decrease in the number of myelinated nerve fibers and an increase in the number of unmyelinated nerve fibers. Based on these observations, Noordenbos (1959) was the first to propose a hypothesis for the generation of PHN: the virus causes a massive loss of fast-conducting coarse nerve fibers, while injurious afferent fine fibers remain or even increase in number, making the coarse and fine nerve fibers disproportionate, and the imbalance of their afferent signals may be the root of the abnormal spontaneous activity of PHN. This is consistent with Melzack and Wall’s (1965) “gate control theory” of pain, in which damage to peripherally myelinated thick fibers relieves the inhibition of injurious afferents and turns on the pain.
Injury to peripheral myelinated thick fibers releases the inhibition of injurious afferents and opens the “gate” for injurious unmyelinated afferents in the dorsal horn of the spinal cord, sensitizing spinal pain-related neurons and causing pain. Further neurophysiological experiments supported this idea by examining the function of coarse and fine afferent fibers in patients with PHN, and some patients showed a significant reduction in vibrioception, indicating that the coarse fibers mediating vibrioception were impaired. In addition to nerves, pathological changes in HZ patients were also evidenced by the destruction of non-neural cells and blood vessels, forming collagen scarring in the skin with almost no cells present; the dendritic cell marker PGP, which plays a key role in the immune response, was positive in the damaged skin of PHN patients and negative in normal skin.
(2) Experimental study: In an early autopsy study, nerve morphology was compared between two groups of PHN patients “with severe pain” and “without pain”. The dorsal root ganglion neurons and their axons were significantly reduced in the “severe pain” patients, and the dorsal horn of the spinal cord was wrinkled [9]. fMRI observations showed abnormal spinal cord and brainstem function in half of the HZ patients. Human peroneal nerve biopsies showed that afferent nerve loss was positively correlated with advancing age, with an average of 8000/mm2 of myelinated nerve fibers in healthy young adults, compared to a significant decrease of 5000/mm2 in older adults, suggesting that nerve fiber reduction is a factor in the high incidence of PHN in the elderly population.
Further support was provided by electrophysiological studies in which electromyography (EMG) evoked by stimulation of cutaneous or muscular nerves was recorded in both “pain” and “no pain” groups of PHN patients, and the amplitude of sensory-related action potentials and motor-related H reflexes were significantly reduced in both groups. amplitude were significantly reduced in both groups, indicating damage to primary afferent and efferent thick myelinated fibers, but there were no statistical differences in electrophysiological indices between the two groups.
Neurophysiological studies have shown that different physiological functions are mediated by different nerve fibers, e.g., peripheral Aβ fibers innervate baroreceptors that mediate vibration perception, axonal-vasodilatory reflexes (skin flushing response) indicate the function of C fibers, and heart rate changes reflect the function of parasympathetic small fibers. The measurement of vibration sensitivity, histamine-induced skin flushing response and heart rate changes in PHN patients can help to reveal the role of Aβ, C and sympathetic fibers in the production of pain in HZ.
When comparing two groups of PHN patients with “pain” and “no pain”, some HZ patients showed significantly dulled vibration sensation in the lower extremities, indicating impairment of Aβ afferents, while there was no difference in C and parasympathetic fiber function between the two groups of PHN patients.
Therefore, acute HZ patients with high vibrogenic thresholds are more likely to develop PHN, and detection of vibrogenic sensation may serve as a predictor of PHN. Results are inconsistent regarding the role of myelinated Aδ and unmyelinated C fibers, which conduct injurious information, in PHN. Laser stimulation of the skin of damaged dermatomes in patients with PHN and extracranial recording of Aδ fiber-mediated laser evoked potentials (LEP) resulted in a significant decrease in LEP amplitude in the damaged side of the skin compared with stimulation of LEP in the contralateral normal skin, but no change in latency.
The change in evoked potential amplitude was positively correlated with the patient’s age, but not with the degree and nature of pain. Therefore, it is believed that the development of PHN is not directly caused by damage to the myelinated fine fibers (Aδ) of the peripheral nerve, but may be due to degeneration of the dorsal root ganglion neurons by viral invasion. Regarding the function of C-fibers, the
Local application of capsaicin induced neurogenic axonal flush reflexes as an indicator of primary afferent C-fiber activity, which were significantly reduced in PHN patients with touch-evoked pain compared with PHN patients without touch-evoked pain, suggesting that touch-evoked pain in PHN patients may be related to impaired primary afferent C-fiber function.
This seems to be inconsistent with the aforementioned finding that C-fibers with histamine-evoked axonal flush reflexes are not involved in PHN pain, a contradiction that may be related to the different amounts of stimulation of C-fibers by microelectrophoretic histamine and topically applied capsaicin, which directly excite a large number of TRPV 1 receptors present on C-fibers, closer to clinical conditions. No conclusive opinion can be reached regarding the peripheral mechanism of PHN pain. For this reason, Fields et al. proposed the concepts of “Irritablenociceptors” and “deafferentation” to explain PHN.
Irritablenociceptors are uninjured susceptible C dorsal root ganglion neurons with peripheral branches innervating the skin and central branches linked to spinal cord targets. Abnormal function and spontaneous activity of these C fibers innervating the skin provide sufficient afferent signals to the center to cause chronic central sensitization. Application of 0.075% capsaicin to PHN skin increased pain and expanded the area of touch-evoked pain, suggesting the presence of “susceptible injury receptors” expressing TRPV1 receptors in the dorsal root ganglion. In addition, removing the skin of the painful area or applying topical lidocaine cream could reduce PHN, which also supported the hypothesis of the involvement of “susceptible receptors”.
2. Animal experiments
(1) Model: In the 1990s, several laboratories successfully established the rat HZ model by inoculating VZV virus into rabbit skin cells (RSC), young hamster kidney cells (BHK-21) or African green monkey kidney fibroblasts (CV-1), and then subcutaneously injecting VZV-infected RSC, BHK21 or CV-1 cells into the soles of the hind limbs of rats. The animals developed HZ symptoms and formed a HZ model . The mouse HZ model was inoculated with HSV-1 virus intradermally. Due to the establishment of HZ animal model, the research of mechanism exploration gradually increased. Recently, an ex vivo cellular model of VZV infection has been developed, providing a new way to explore the mechanism of HZ in depth.
(2) Peripheral mechanism: PHN belongs to the category of neuropathic pain, and like other neuropathic pain, neuroplasticity is the basis of PHN production, and the alteration of gene expression in dorsal root ganglion neurons is one of the key factors affecting plasticity. In neuropathic pain conditions, damage to sensory nerves induces neurochemical, physiological, and anatomical changes in primary sensory neurons and central neurons, such as long buds in afferent terminals, loss of inhibitory neurons, accumulation of Na channels causing hyperexcitability, downregulation of TTX-insensitive sodium channels Nav 1.8, and upregulation of TTX-insensitive Nav1.3.
These plasticity changes in neuropathic pain conditions also occurred in the HZ model rats as well. Immunohistochemistry and protein blotting experiments showed that the neural injury markers ATF-3, calcium channel subunit α2δ1, sodium channel subunits Nav1.3 and Nav 1.8, neuropeptide Y (NPY) and galanin were significantly upregulated in VZV-infected rat dorsal root ganglion neurons.
The VZV immediate-early gene protein IE 62 was expressed in both A and C fibers, and immunohistochemistry showed that IE 62 was co-expressed with the A fiber marker NF-200 and the C fiber marker peripherin, respectively [26]. In the scarred skin of PHN mice, the number of C fibers and peripherin-positive C class dorsal root ganglion neurons expressing CGRP was reduced, whereas NF200-positive A fibers and dorsal root ganglion neurons were unchanged, thus suggesting that the development of PHN is associated with C fiber damage [27]. The morphological observations of these animals are not consistent with the previously described functional findings of nerve fibers in PHN patients and still need further experimental clarification. Genetic knockout of the prostaglandin E2 (PGE2) receptor EP3 or application of EP3 antagonists significantly attenuated acute herpes zoster pain and reduced the incidence of PHN. During acute episodes of herpes zoster pain, increased levels of PGE2 and immunopositive COX-2 on the nuclear membrane of dorsal root ganglion neurons were observed in virus-infected dorsal root ganglia.
COX inhibitors dose-dependently attenuated acute herpetic pain, but in the later PHN phase, PGE2 levels and COX-2 mRNA were similar to those of wild mice. These results suggest that COX-2 and EP3 are involved in the production of acute herpes zoster pain, but not in its maintenance and the development of late PHN. Knockdown or pharmacological blockade of the NMDA receptor for glutamate significantly slowed neuropathic pain, suggesting an important role for the NMDA receptor in neuropathic pain formation.
In addition the role of NMDA receptors has also received attention. The NR2B subunit of the NMDA receptor is the predominant tyrosine phosphorylated protein in the nervous system and is mainly expressed in peripheral unmyelinated fine nerve fibers, while Tyr1472 phosphorylation of the NR2B subunit plays an important role in peripheral nerve fiber injury. play an important role in injury.
In animal experiments, Tyr1472 knock-in Phe was used to interfere with the phosphorylation of NR2B receptor Tyr1472, and NR2B receptor phosphorylation was blocked in mutant mice bred by Phe knock-in (Y1472F-KI). The development of HZ was observed by inoculating the soles of the hind limbs of Y1472F-KI mutant and wild mice with herpes simplex virus type 1 (HSV-1). Both types of mice developed acute herpes zoster and touch-induced pain 7 days after inoculation. However, 45 days after inoculation, the intensity and incidence of touch-induced pain were significantly lower in Y1472F-KI mice compared with wild mice, but the nerve branching in the skin of Y1472F-KI mice was still more extensively preserved.
However, the nerve branching in the skin of Y1472F-KI mice was still more extensively preserved, suggesting that these changes in Y1472F-KI mice were caused by blocked phosphorylation of NR2B receptors expressed on nerve fibers. Moreover, dorsal root ganglion neurons of wild mice were more sensitive to glutamate toxicity than Y1472F-KI mice. In Y1472F-KI mice not only reduced viral damage to cutaneous nerves, but also accelerated regeneration of damaged nerve fibers. These results suggest that peripheral neurons NR2B are involved in the production of acute herpes zoster pain and post-herpetic neuralgia.
(3) Central mechanisms: The central mechanisms of neuropathic pain have been studied extensively, but the available data on PHN as a type of neuropathic pain suggest that VZV mainly affects peripheral afferents and that there are few reports of central effects. NMDA receptors for glutamate, the predominant central excitatory transmitter, mediate neuropathic pain. Early clinical studies noted that the NMDA receptor antagonist lorazepam relieved pain in patients with PHN. In a HZ rat model, spinal application of NMDA receptor-specific antagonists significantly attenuated herpes zoster-induced touch-evoked pain, further confirming that NMDA receptors also play an important role in PHN formation. Glycine is an important inhibitory transmitter of the nervous system and is also involved in the formation of neuropathic pain.
Recent studies on HZ and PHN in mice have shown that spinal administration of GlyT2 (neurogenic glycine transporter) inhibitors significantly attenuated touch-evoked pain in acute and chronic herpes zoster, whereas GlT1 (gliadin-derived glycine transporter) inhibitors were ineffective.GlyT2 is a glycine reuptake transporter that regulates the extracellular concentration of glycine, and GlyT2 inhibitors increase glycine accumulation at inhibitory GlyT2 inhibitors increase the accumulation of glycine at inhibitory synaptic sites, enhance inhibitory synaptic transmission, and attenuate spinal pain-sensitive neuronal activity. Therefore, GlyT2 could be a target for the treatment of HZ and PHN.
Galactose-binding lectin-3 (galectin-3), a member of the β-galactose-binding lectin family, is secreted by monocytes, phagocytes and epithelial cells and is involved in biological processes such as cellular interactions, cell cycle, cell growth regulation, mRNA precursor splicing and angiogenesis. Expression of mRNA and protein of galectin-3 was significantly increased in the dorsal horn of the spinal cord of mice after HSV-1 infection. galectin-3 gene deficient mice or intrathecal injection of galectin-3 antibody significantly reduced touch-induced pain, suggesting that galectin-3 is involved in the production of PHN pain. Pathological examination of patients with herpes zoster pain showed inflammatory changes in the spinal cord and angular segmental atrophy, suggesting viral expansion along the dorsal roots into the spinal cord.
Galectin-3 was co-labeled with the phagocytic marker F4/80 and the microglial cell marker Iba-1, but not with neurons and astrocytes. galectin-3 may mediate herpes zoster pain through phagocytes and microglia. These results suggest that galectin-3 may serve as a new target for the treatment of acute herpetic pain. In addition, significant increases in interleukin-8 and interleukin-6 levels in the cerebrospinal fluid of patients with PHN have been reported, and human histocompatibility leukocyte antigen (HLA) monomers are very closely associated with the development of PHN, and these changes may be useful as a clinical tool for predicting PHN.
II. Clinical treatment
There is no specific drug for the treatment of postherpetic neuralgia (PHN), and traditional analgesics are often ineffective. Since PHN belongs to the category of neuropathic pain, conventional treatments for neuropathic pain have some effect on it. At present, acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) are often used for mild pain in HZ patients. Severe pain is treated with opioids (morphine or tramadol), and if it is still not controlled, gabapentin or pregabalin, tricyclic antidepressants or steroids are added.
1.Anti-viral drugs
Acyclovir (aciclovir), valaciclovir (valaciclovir), famciclovir (famciclovir). For acute HZ, systemic administration within 72 hours of rash onset is required to reduce symptoms and pain. The mechanism of action is that the drug is phosphorylated to triphosphate by viral thymidine kinase and cellular kinase, thereby inhibiting the replication of the virus.
2. Tricyclic antidepressants (TCAs)
These drugs block the reuptake of norepinephrine and 5-hydroxytryptamine and enhance the inhibition of spinal cord injury neurons. In addition, TCAs also inhibit adrenergic sensitization and ectopic firing of peripheral nerves in patients with PHN by blocking adrenergic alpha receptors and sodium channels. Patients with PHN given desipramine, amitriptyline, or fluoxetine titrated over three consecutive weeks had an analgesic effect in 47%, 38%, and 35% of patients, respectively. The percentage of patients with significant analgesic effect was 80%, 53% and 33% for the three drugs respectively, with the best effect being desipramine. if used in combination with opioids, the analgesic effect should be better than that of a single drug.
3.Anti-convulsant drugs
Gabapentin and pregabalin are the first-line drugs for PHN. gabapentin targets the α2δ subunit of voltage-gated calcium channels, which binds to α2δ at presynaptic terminals and reduces calcium influx, thereby inhibiting the release of substance P and glutamate, which mediate peripheral injurious messages. The drug is slowly absorbed and its peak effect is 3-4 hours after administration. It does not bind to plasma proteins, so it does not interact with other drugs. The daily dose of pregabalin is an analogue of γ-aminobutyric acid, which is absorbed quickly, and the dose is 150-600 mg per day.
4.Opioids
Commonly used drugs are tramadol (Tramadol), morphine, oxycodone (oxycodone) and methadone (Methadone). Due to the side effects of opioids, they are included as second or third line drugs in the treatment of PHN. Tramadol inhibits norepinephrine reuptake and enhances 5-hydroxytryptamine release at spinal levels at a dosage of 100-400 mg per day, morphine at less than 200 mg per day, and oxycodone and methadone at an average dosage of 45 mg and 15 mg per day, respectively. In addition, TRK-820 is a new opioid K receptor agonist. In acute HZ mice, TRK-820 was administered in the spinal cord and brain to significantly reduce touch-evoked pain and nociceptive hyperalgesia without affecting motor function. 0.03 mg/kg of TRK-820 had similar analgesic effects to 20 mg/kg of morphine and lasted longer. However, no clinical application has been reported.
5.Local use
Non-steroidal anti-inflammatory drugs (NSAIDS), local anesthetics (lidocaine) and capsaicin patches were used. As an example, capsaicin treatment was applied to elderly patients with PHN for 6 weeks, and 80% of patients showed significant pain reduction [45]. Two new patches containing high concentrations of capsaicin, Qutenza (8%) and NGX-1998 (10% and 20%), had a more pronounced analgesic effect. The analgesic effect was evident 5 minutes after the use of NGX-1998 in patients with PHN [46].
6. Sympathetic blockade
Local anesthetic blockade of sympathetic nerves significantly reduces acute pain in HZ, but has a poor effect on chronic PHN pain. Conversely, injection of sympathetic agonists epinephrine and phenylephrine (phenylephrine) into the skin of painful areas of PHN patients significantly increased the intensity of pain in the injection area and touch-evoked pain in the adjacent non-injected skin. This result is consistent with the enhanced sensitivity of adrenergic nerve fibers induced by nerve injury in animal experiments [47].
7. other drugs
Botulinum toxin, honeybee toxin, vitamins B1, B12 and D, lidocaine (carbamazepine), benzydamine, NMDA receptor blockers (memantine or dextromethorphan, lorazepam, fluphenazine, mexiletine), and H3 receptor antagonists (GSK189254) and cyclooxygenase inhibitors (COX-2) also have some analgesic effects in clinical practice.
8.Acupuncture and transcutaneous electrical nerve stimulation (TENS).
9.Surgery
Removal of the access area from the dorsal root to the dorsal horn of the spinal cord in patients with PHN can significantly reduce pain. Removal of the skin of patients with PHN after severe pain, skin replacement, or transplantation of peripheral sensory nerves on damaged dermatomes can relieve pain [50]. However, such procedures have not been routinely applied. In addition, although gene therapy has not yet been applied clinically, in animal experiments, transcription of enkephalin (ENK) into the dorsal root ganglion of PHN rats significantly attenuated the second-phase response to formaldehyde pain, suggesting that gene therapy has the prospect of application, and VZV vaccination has some effect in preventing the occurrence of HZ, which is not widely used clinically but worth further exploration.
Recent research in China
Similar to the international HZ and PHN research reports, the relevant reports in China are almost limited to clinical treatment. Faced with the advantages of a large number of patients, China has applied a variety of treatment measures and made promising progress. There are 12,690 articles on “Herpes zoster” in the Chinese Academic Journals Online Publishing Database on the China Knowledge Network.
The Chinese Journal of Pain Medicine, for example, has 82 articles on herpes zoster since its inception, and the number of articles is increasing every year. The articles cover dozens of therapeutic measures, such as, nerve blocks (spinal nerve root, dorsal root ganglion, trigeminal ganglion, and sympathetic nerve); medications (antivirals, antidepressants and antiepileptics, analgesics); anhydrous ethanol and adriamycin paravertebral injections; antivirals combined with intradermal injections or intercostal nerve blocks; ozone combined with Depo-Provera; oxycodone and gabapentin.
Linear polarized light NIR irradiation combined with nerve block; paravertebral spinal nerve root block combined with pregabalin or cowpox vaccinated rabbit inflammatory skin extract (neurotoxin); dorsal root ganglion pulsed radiofrequency combined with pregabalin treatment; dorsal root ganglion adriamycin intervention; water cooled radiofrequency treatment; neurotoxin combined with narrow wave UVB methylene blue paravertebral nerve root injection; neurotoxin combined with IR polarized light irradiation; intervertebral foraminal nerve block combined with infrared polarized light; radiofrequency thermal coagulation combined with neurotropine; prostaglandin injection; epidural injection method combined with CQY-B type treatment device irradiation; fentanyl transdermal patch (Doregis); selective acupuncture pinch points plus local percutaneous acupuncture and body acupuncture combined with low frequency electrotherapy, etc. These above treatments can be summarized as: nerve block, drug therapy, drug combined with nerve block, physical therapy, drug and physical therapy combination and acupuncture.
Although none of these treatments have achieved ideal results, the early diagnosis of herpes zoster and early comprehensive treatment have significantly reduced the incidence of sleep affective index (SIS), pain level (VAS) and post-acute pain. This suggests that early diagnosis and comprehensive treatment can not only reduce acute symptoms, but also reduce the incidence of postherpetic neuralgia (PHN) and improve the quality of life of patients. In addition to a large number of clinical treatments, a small number of basic clinical studies have been conducted.
A systematic observation of the degree and nature of pain, clinical type, residual symptoms in the affected area and concomitant symptoms in several hundred patients with PHN has been reported, with patients complaining of spontaneous lightning-like pain, knife-like pain, burning pain, pinprick-like pain and mixed pain being the most common. The mean VAS score was 6.8. The clinical presentation was variable in four types: agitated (57.14%), paralyzed (22.16%), integrated (17.93%), and nonagitated (2.77%).
The quality of life and work ability of patients were significantly affected. It provides a basis for clinical diagnosis and treatment. A study of skin sensory changes in patients with PHN showed that the thresholds for cold, heat, and thermal pain were elevated in the damaged skin, with the most pronounced increase in the cold threshold and a negative correlation between the cold and heat thresholds. These results suggest that the peripheral Aδ and C nerve fibers are more damaged during the development of the lesion, and the Aδ nerve fibers that conduct cold sensation are more severely damaged. In a recent article published in a foreign journal, Chinese scholars have revealed the role of immune T cells in the formation of herpes zoster pain.
Conclusion: Herpes zoster (HZ) and postherpetic neuralgia (PHN) are persistent diseases with high incidence, difficult to treat, and serious health risks. Its incidence is proportional to age, and 70% of PHN patients not only have severe tenderness pain, but also have sleep disorders, emotional depression and melancholy, resulting in a reduced quality of life, and people with a history of herpes zoster are more likely to have a stroke in old age.
Today, as our country is rapidly aging, it is urgent to investigate the mechanism and clinical study of PHN. It also provides us with more opportunities for exploration, and the number of articles published by our scholars is almost close to the total number of articles published in all countries in the world. We should make full use of the advantage of having many research subjects to strive for breakthroughs in the research and treatment of herpes zoster pain and make new contributions to the health of mankind.