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| == Postherpetic neuralgia == | | {{Short description|A chronic pain condition following shingles}} |
| | {{Use dmy dates|date=October 2023}} |
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| {{redirect|PHN}}
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| {{Infobox medical condition (new) | | {{Infobox medical condition (new) |
| | name = Postherpetic neuralgia | | | name = Postherpetic neuralgia |
| | synonyms = | | | synonyms = PHN |
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| | pronounce = | | | pronounce = |
| | field = | | | field = [[Neurology]], [[Pain management]] |
| | symptoms = burning or stabbing pain, pain doesn't go after [[shingles]]. | | | symptoms = Burning, stabbing, or shooting pain that persists after resolution of [[shingles]] rash; sensitivity to touch (allodynia); numbness or itching |
| | complications = | | | complications = Chronic pain, [[depression]], [[sleep disturbance]], reduced quality of life |
| | onset = | | | onset = Typically begins after shingles rash resolves (weeks to months after initial infection) |
| | duration = lifelong | | | duration = Lifelong or prolonged in some cases |
| | types = | | | types = Localized to the area affected by shingles, usually thoracic or trigeminal distribution |
| | causes = | | | causes = Nerve damage following [[varicella-zoster virus]] reactivation ([[herpes zoster]]) |
| | risks = | | | risks = Age >60 years, severe shingles rash, delayed treatment of shingles, immunosuppression |
| | diagnosis = | | | diagnosis = Clinical history and symptoms following shingles; physical examination |
| | differential = | | | differential = Diabetic neuropathy, trigeminal neuralgia, other causes of chronic nerve pain |
| | prevention = | | | prevention = [[Shingles vaccine]] (e.g., [[Shingrix]]) |
| | treatment = | | | treatment = [[Topical lidocaine]], [[capsaicin cream]], nerve blocks, [[cognitive behavioral therapy]] |
| | medication = | | | medication = [[Gabapentin]], [[pregabalin]], [[tricyclic antidepressants]] (e.g., [[amitriptyline]]), [[opioids]] (for severe cases) |
| | prognosis = | | | prognosis = Variable; may resolve over months or become chronic and debilitating |
| | frequency = | | | frequency = Affects ~10–20% of people with shingles; risk increases with age |
| | deaths = | | | deaths = Rare, usually due to complications like severe depression or suicide in extreme cases |
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| <!-- Definition and symptoms -->
| | '''Postherpetic neuralgia''' (PHN) is a chronic pain condition that occurs as a complication of [[herpes zoster]], commonly known as [[shingles]]. It is characterized by persistent nerve pain in the area where the shingles rash appeared, even after the rash has healed. PHN is the most common long-term complication of shingles and can significantly affect a person's quality of life. |
| '''Postherpetic neuralgia''' ('''PHN''') is [[neuropathic pain]] which occurs due to damage to a peripheral nerve caused by the reactivation of the [[varicella zoster virus]] ([[herpes zoster]], also known as '''shingles'''). Typically, the nerve pain (neuralgia) is confined to an area of skin innervated by a single [[sensory nerve]], which is known as a [[dermatome (anatomy)|dermatome]]. PHN is defined as dermatomal nerve pain that persists for more than 90 days after an outbreak of herpes zoster affecting the same dermatome.<ref name="Johnson2014"/> Several types of pain may occur with PHN including continuous burning pain, episodes of severe shooting or electric-like pain, and a heightened sensitivity to gentle touch which would not otherwise cause pain (mechanical [[allodynia]]) or to painful stimuli ([[hyperalgesia]]).<ref name="Johnson2014"/> [[Paresthesia|Abnormal sensations]] and [[pruritus|itching]] may also occur.<ref name="Johnson2014"/> | |
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| | ==Pathophysiology== |
| | Postherpetic neuralgia results from damage to the [[nervous system]] caused by the [[varicella-zoster virus]] (VZV), the same virus that causes [[chickenpox]]. After a person recovers from chickenpox, the virus remains dormant in the [[dorsal root ganglia]] of the [[spinal cord]]. Years later, the virus can reactivate, leading to shingles. In some individuals, the nerve damage from the viral reactivation results in chronic pain, known as postherpetic neuralgia. |
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| | ==Symptoms== |
| | The primary symptom of postherpetic neuralgia is pain in the area where the shingles rash occurred. This pain can be described as burning, stabbing, or aching. Other symptoms may include: |
| | * Allodynia: Pain from stimuli that do not normally provoke pain, such as light touch or temperature changes. |
| | * Hyperalgesia: Increased sensitivity to painful stimuli. |
| | * Itching or numbness in the affected area. |
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| <!-- Cause and Pathophysiology -->
| | ==Risk Factors== |
| The nerve pain of PHN is thought to result from damage in a peripheral nerve which was affected by the reactivation of the varicella zoster virus or troubles after chemotherapy. PHN typically begins when the herpes zoster [[vesicle (dermatology)|vesicle]]s have crusted over and begun to heal, but can begin in the absence of herpes zoster—a condition called ''zoster sine herpete''.
| | Several factors increase the risk of developing postherpetic neuralgia, including: |
| | | * Age: Older adults are more likely to develop PHN. |
| <!-- Prevention and Treatment -->
| | * Severity of the shingles rash: A more severe rash increases the risk. |
| There is no treatment which modifies the disease course of PHN; therefore, controlling the affected person's symptoms is the main goal of treatment. Medications applied to the skin such as [[capsaicin]] or topical [[anesthetic]]s (e.g., [[lidocaine]]) are used for mild pain and can be used in combination with oral medications for moderate to severe pain.<ref name="Johnson2014"/> Oral [[anticonvulsant]] medications such as [[gabapentin]] and [[pregabalin]] are also approved for treatment of PHN.<ref name="Johnson2014"/> [[Tricyclic antidepressant]]s reduce PHN pain but their use is limited by side effects.<ref name="Johnson2014"/> [[Opioid]] medications are not generally recommended for treatment except in specific circumstances and under the care of a pain specialist due to mixed evidence of efficacy and concerns about potential for [[opioid use disorder|abuse and addiction]].<ref name="Johnson2014"/>
| | * Delay in antiviral treatment: Early treatment of shingles with antiviral medications can reduce the risk of PHN. |
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| <!-- Epidemiology -->
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| PHN is the most common long-term complication of herpes zoster.<ref name="Johnson2014">{{cite journal|last1=Johnson|first1=RW|last2=Rice|first2=AS|title=Clinical practice. Postherpetic neuralgia|journal=New England Journal of Medicine|date=October 2014|volume=371|issue=16|pages=1526–33|doi=10.1056/NEJMcp1403062|pmid=25317872|type=Review}}</ref> The incidence and prevalence of PHN are uncertain due to varying definitions. Approximately 20% of people affected by herpes zoster report pain in the affected area three months after the initial episode of herpes zoster and 15% of people similarly report this pain two years after the herpes zoster rash.<ref name="Johnson2014"/> Since herpes zoster occurs due to reactivation of the varicella zoster virus, which is more likely to occur with a [[immunocompromised|weakened immune system]], both herpes zoster and PHN occur more often in the elderly and in people with [[diabetes mellitus]].<ref name="Johnson2014"/> Risk factors for PHN include older age, a severe herpes-zoster rash, and pain during the herpes zoster episode.<ref name="Johnson2014"/> PHN is often very painful and can be quite debilitating. Affected individuals often experience a decrease in their [[quality of life]].<ref name="Johnson2014"/>
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| ==Signs and symptoms==
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| Symptoms:
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| * With resolution of the herpes zoster eruption, pain that continues for three months or more is defined as postherpetic neuralgia. | |
| * Pain is variable, from discomfort to very severe, and may be described as burning, stabbing, or gnawing.
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| Signs:
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| * Area of previous herpes zoster may show evidence of [[cutaneous]] scarring.
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| * Sensation may be altered over the areas involved, in the form of either hypersensitivity or decreased sensation.
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| * In rare cases, the patient might also experience muscle weakness, tremor, or paralysis if the nerves involved also control muscle movement. | |
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| ==Pathophysiology==
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| Postherpetic neuralgia is thought to be due to nerve damage caused by herpes zoster. The damage causes nerves in the affected [[dermatomic area]] of the skin to send abnormal electrical signals to the brain. These signals may convey excruciating [[pain]], and may persist or recur for months, years, or for life.<ref name="McMahon Publishing">{{cite web|last1=Gharibo|first1=Christopher|last2=Kim|first2=Carolyn|title=Neuropathic Pain of Postherpetic Neuralgia|url=http://www.painmedicinenews.com/download/PostNeuralgiaPMN0411_WM.pdf|website=Pain Medicine News|publisher=McMahon Publishing|accessdate=6 October 2014|date=December 2011}}</ref>
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| A key factor in the neural plasticity underlying neuropathic pain is altered gene expression in sensory [[dorsal root ganglia]] [[neuron]]s. Injury to sensory nerves induces neurochemical, physiological, and anatomical modifications to afferent and central neurons, such as afferent terminal sprouting and inhibitory [[interneuron]] loss.<ref name="McMahon Publishing"/> Following nerve damage, NaCl channel accumulation causes hyperexcitability, and downregulation of the TTX-resistant Nav1.8 (sensory neuron specific, SNS1) channel and upregulation of TTX-sensitive Nav1.3 (brain type III) and [[TRPV1]] channels. These changes contribute to increased [[NMDA]] glutamate receptor-dependent excitability of spinal dorsal horn neurons and are restricted to the ipsilateral (injured) side. A combination of these factors could contribute to the neuropathic pain state of postherpetic neuralgia.
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| ==Diagnosis== | | ==Diagnosis== |
| Lab Studies:
| | Diagnosis of postherpetic neuralgia is primarily clinical, based on the patient's history of shingles and the presence of persistent pain in the affected area. A thorough [[medical history]] and [[physical examination]] are essential to rule out other causes of chronic pain. |
| * No laboratory work is usually necessary.
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| * Results of [[cerebrospinal fluid]] evaluation are abnormal in 61%.
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| ** [[Pleocytosis]] is observed in 46%, elevated protein in 26%, and VZV DNA in 22%.
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| * These findings are not predictive of the clinical course of postherpetic neuralgia.
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| * Viral culture or [[immunofluorescence]] staining may be used to differentiate herpes simplex from herpes zoster in cases that are difficult to distinguish clinically.
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| * [[Antibodies]] to herpes zoster can be measured. A 4-fold increase has been used to support the diagnosis of subclinical herpes zoster (zoster sine herpete). However, a rising titer secondary to viral exposure rather than reactivation cannot be ruled out.
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| Imaging studies:
| | ==Treatment== |
| * [[Magnetic resonance imaging]] lesions attributable to herpes zoster were seen in the brain stem and cervical cord in 56% (9/16) of patients. | | Treatment of postherpetic neuralgia focuses on pain management and improving quality of life. Options include: |
| * At three months after onset of herpes zoster, 56% (5/9) of patients with an abnormal magnetic resonance image had developed postherpetic neuralgia. | | * [[Anticonvulsants]]: Medications such as [[gabapentin]] and [[pregabalin]] can help reduce nerve pain. |
| * Of the seven patients who had no herpes-zoster-related lesions on the magnetic resonance image, none had residual pain. | | * [[Antidepressants]]: Tricyclic antidepressants like [[amitriptyline]] may be effective in managing pain. |
| | * Topical treatments: Lidocaine patches or capsaicin cream can provide localized pain relief. |
| | * [[Opioids]]: In some cases, opioids may be prescribed for severe pain, but they are generally used with caution due to the risk of dependence. |
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| ==Prevention== | | ==Prevention== |
| | | The most effective way to prevent postherpetic neuralgia is through vaccination. The [[shingles vaccine]], such as [[Shingrix]], is recommended for older adults to reduce the risk of developing shingles and its complications, including PHN. |
| ===Primary prevention===
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| In 1995, the [[Food and Drug Administration]] (FDA) approved the [[Varicella vaccine]] to prevent chickenpox. Its effect on postherpetic neuralgia is still unknown. The vaccine—made from a weakened form of the varicella-zoster virus—may keep chickenpox from occurring in nonimmune children and adults, or at least lessen the risk of the varicella zoster virus lying dormant in the body and reactivating later as shingles. If shingles could be prevented, postherpetic neuralgia could be completely avoided.
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| In May 2006 the [[Advisory Committee on Immunization Practices]] approved a new vaccine by Merck ([[Zostavax]]) against shingles. This vaccine is a more potent version of the [[varicella vaccine|chickenpox vaccine]], and evidence shows that it reduces the incidence of postherpetic neuralgia.<ref>{{cite journal |vauthors=Chen N, Li Q, Zhang Y, Zhou M, Zhou D, He L |title=Vaccination for preventing postherpetic neuralgia |journal=Cochrane Database Syst Rev |volume= |issue=3 |pages=CD007795 |year=2011 |pmid=21412911 |doi=10.1002/14651858.CD007795.pub2 |editor1-last=He |editor1-first=Li}}</ref> The CDC recommends use of this vaccine in all persons over 60 years old.<ref>https://www.cdc.gov/vaccines/vpd-vac/shingles/default.htm{{full|date=September 2018}}</ref>
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| The most effective means of preventing PHN from a herpes zoster infection is prior vaccination with the varicella vaccine. Vaccination decreases the overall incidence of virus reactivation but also decreases the severity of disease development and incidence of PHN if reactivation does occur.<ref>Benzon H, et.al. Essentials of Pain Medicine. 3rd edition. 2011.</ref>
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| ===Secondary prevention===
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| A 2013 Cochrane [[meta-analysis]] of 6 randomized controlled trials (RCTs) investigating oral antiviral medications given within 72 hours after the onset of herpes zoster rash in immunocompetent people for preventing postherpetic neuralgia (PHN) found no significant difference between placebo and [[acyclovir]].
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| Additionally, there was no significant difference in preventing the incidence of PHN found in the one RCT included in the meta-analysis that compared placebo to oral [[famciclovir]] treatment within 72 hours of HZ rash onset. Studies using [[valacyclovir]] treatment were not included in the meta-analysis.
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| PHN was defined as pain at the site of the dermatomic rash at 120 days after the onset of rash, and incidence was evaluated at 1, 4, and 6 months after rash onset. Patients who are prescribed oral antiviral agents after the onset of rash should be informed that their chances of developing PHN are no different than those not taking oral antiviral agents.<ref name="pmid24500927">{{cite journal |vauthors=Chen N, Li Q, Yang J, etal |title=Antiviral treatment for preventing postherpetic neuralgia |journal=Cochrane Database Syst Rev |volume= 2|issue=2 |pages=CD006866 |year=2014 |pmid=24500927 |doi=10.1002/14651858.CD006866.pub3 |editor1-last=He |editor1-first=Li}}</ref>
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| ==Treatment==
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| The pain from postherpetic neuralgia can be very severe and requires immediate treatment. There is no treatment which modifies the course of the disease and management primarily aims to control symptoms.<ref name="Johnson2014"/>
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| ===Medications===
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| ====Topical medications====
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| Medications applied to the skin can be used alone if the pain from PHN is mild or in combination with oral medications if the pain is moderate to severe.<ref name="Johnson2014"/> Topical medications for PHN include low-dose (0.075%) and high-dose (8%) [[capsaicin]] and [[anesthetic]]s such as [[lidocaine]] patches.<ref name="Johnson2014"/> Lidocaine patches (5% concentration) are approved in the United States and Europe to treat PHN though evidence supporting their use is limited.<ref name="Johnson2014"/> A [[meta-analysis]] of multiple small [[placebo]]-controlled [[randomized controlled trial]]s found that for every two people treated with topical lidocaine, one person experienced at least a 50% reduction in their PHN-associated pain ([[number needed to treat|number needed to treat (NNT)]]=2).<ref name="Hempenstall2005">{{cite journal|last1=Hempenstall|first1=K|last2=Nurmikko|first2=TJ|last3=Johnson|first3=RW|last4=A'Hern|first4=RP|last5=Rice|first5=AS|title=Analgesic therapy in postherpetic neuralgia: a quantitative systematic review|journal=PLoS Medicine|date=July 2005|volume=2|issue=7|page=e164|pmid=16013891|pmc=1181872|type=Systematic Review and Meta-Analysis|doi=10.1371/journal.pmed.0020164}}</ref>
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| Low-dose capsaicin may be useful for reducing PHN-associated pain but is limited by side effects ([[erythema|redness]] and a burning or stinging sensation with application) and the need to apply it four times daily.<ref name="Johnson2014"/> Approximately three people must be treated with low-dose capsaicin cream for one person to experience significant pain relief (number needed to treat =3.3).<ref name="Johnson2014"/><ref name="Hempenstall2005"/> A single topical application of a high-dose capsaicin patch over the affected area after [[Anesthesia|numbing the area]] with a topical anesthetic has also been found to relieve PHN-associated pain.<ref name="Johnson2014"/> For every eleven people treated with a high-dose capsaicin patch for up to 12 weeks, one person experienced a significant improvement in their pain. (number needed to treat=11).<ref name="Derry2017">{{cite journal|last1=Derry|first1=S|last2=Rice|first2=AS|last3=Cole|first3=P|last4=Tan|first4=T|last5=Moore|first5=RA|title=Topical capsaicin (high concentration) for chronic neuropathic pain in adults|journal=Cochrane Database of Systematic Reviews|date=January 2017|volume=1|page=CD007393|doi=10.1002/14651858.CD007393.pub4|pmid=28085183|pmc=6464756|type=Systematic Review and Meta-Analysis}}</ref> Due to the need for topical anesthesia before application of the high-dose capsaicin patch, referral to a pain specialist is generally recommended if this approach is being considered.<ref name="Johnson2014"/>
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| ====Oral medications====
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| Multiple oral medications have demonstrated efficacy in relieving postherpetic neuralgia pain. [[Tricyclic antidepressant]]s (TCAs), such as [[nortriptyline]] or [[desipramine]], are effective in reducing postherpetic neuralgia pain but are limited by their numerous side effects. For every three people treated with a tricyclic antidepressant, one person is expected to have a clinically significant reduction in their pain (NNT=3).<ref name="Johnson2014"/> Additionally, of every sixteen people treated with a TCA, one person is expected to stop the medication due to a bothersome side effect, such as [[xerostomia|dry mouth]], [[constipation]], or [[urinary retention]] ([[number needed to harm]]=16).<ref name="Johnson2014"/> The [[anticonvulsant]] medications [[pregabalin]] and [[gabapentin]] also effectively relieve postherpetic neuralgia pain. Treatment with pregabalin leads to a reduction in pain intensity of 50% or more in one person out of every 4-5 people treated (NNT=4-5).<ref name="Wiffen2013">{{cite journal|last1=Wiffen|first1=PJ|last2=Derry|first2=S|last3=Moore|first3=RA|last4=Aldington|first4=D|last5=Cole|first5=P|title=Antiepileptic drugs for neuropathic pain and fibromyalgia - an overview of Cochrane reviews|journal=Cochrane Database of Systematic Reviews|date=November 2013|volume=11|issue=CD010567|pages=CD010567|doi=10.1002/14651858.CD010567.pub2|pmid=24217986|pmc=6469538|type=Systematic Review and Meta-Analysis}}</ref> Similarly, treatment with gabapentin also leads to a 50% reduction in pain intensity in one person out of every 7-8 people treated (NNT=7.5).<ref name="Wiffen2013"/>
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| Opioids such as [[tramadol]], [[methadone]], [[oxycodone]], and [[morphine]] have not been well-studied for postherpetic neuralgia treatment.<ref name="Duehmke2017">{{cite journal|last1=Duehmke|first1=RM|last2=Derry|first2=S|last3=Wiffen|first3=PJ|last4=Bell|first4=RF|last5=Aldington|first5=D|last6=Moore|first6=RA|title=Tramadol for neuropathic pain in adults|journal=Cochrane Database of Systematic Reviews|date=June 2017|volume=6|issue=CD003726|pages=CD003726|doi=10.1002/14651858.CD003726.pub4|pmid=28616956|pmc=6481580|type=Systematic Review & Meta-Analysis}}</ref><ref name="McNicol2017">{{cite journal|last1=McNicol|first1=ED|last2=Ferguson|first2=MC|last3=Schumann|first3=R|title=Methadone for neuropathic pain in adults|journal=Cochrane Database of Systematic Reviews|date=May 2017|volume=5|issue=CD012499|pages=CD012499|doi=10.1002/14651858.CD012499.pub2|pmid=28514508|pmc=6353163|type=Systematic Review & Meta-Analysis}}</ref><ref name="Cooper2017">{{cite journal|last1=Cooper|first1=TE|last2=Chen|first2=J|last3=Wiffen|first3=PJ|last4=Derry|first4=S|last5=Carr|first5=DB|title=Morphine for chronic neuropathic pain in adults|journal=Cochrane Database of Systematic Reviews|date=May 2017|volume=5|issue=CD011669|pages=CD011669|doi=10.1002/14651858.CD011669.pub2|pmid=28530786|pmc=6481499|type=Systematic Review & Meta-Analysis}}</ref><ref name="Gaskell2016">{{cite journal|last1=Gaskell|first1=H|last2=Derry|first2=S|last3=Stannard|first3=C|last4=Moore|first4=RA|title=Oxycodone for neuropathic pain in adults|journal=Cochrane Database of Systematic Reviews|date=July 2016|volume=7|issue=CD010692|pages=CD010692|doi=10.1002/14651858.CD010692.pub3|pmid=27465317|pmc=6457997|type=Systematic Review & Meta-Analysis}}</ref> [[Acetaminophen]] and [[nonsteroidal anti-inflammatory drug]]s are thought to be ineffective and have not undergone rigorous study for PHN.<ref name="Johnson2014"/><ref name="Wiffen2016">{{cite journal|last1=Wiffen|first1=PJ|last2=Knaggs|first2=R|last3=Derry|first3=S|last4=Cole|first4=P|last5=Phillips|first5=T|last6=Moore|first6=RA|title=Paracetamol (acetaminophen) with or without codeine or dihydrocodeine for neuropathic pain in adults|journal=Cochrane Database of Systematic Reviews|date=December 2016|volume=12|issue=CD012227|pages=CD012227|doi=10.1002/14651858.CD012227.pub2|pmid=28027389|pmc=6463878|type=Systematic Review & Meta-Analysis}}</ref>
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| ==Prognosis== | | ==Prognosis== |
| The natural history of postherpetic neuralgia involves slow resolution of the pain syndrome. A subgroup of affected individuals may develop severe, long-lasting pain that does not respond to medical therapy. | | The prognosis for individuals with postherpetic neuralgia varies. While some people experience a gradual reduction in pain over time, others may have persistent pain for months or even years. Early intervention and effective pain management strategies can improve outcomes. |
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| ==Epidemiology==
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| In the United States each year approximately 1,000,000 individuals develop herpes zoster.<ref>{{cite book|title=Sauer's Manual of Skin Diseases|author1=Brian J. Hall |author2=John C. Hall |publisher=Lippincott Williams & Wilkins, 2010|chapter=Infectious diseases in the skin|page=232}}</ref> Of those individuals, approximately 10-18% develop postherpetic neuralgia.<ref>{{cite journal|last1=Weaver|first1=B A|title=Herpes zoster overview: natural history and incidence.|journal=J Am Osteopath Assoc|date=2009|volume=109|issue=6 (Suppl 2)|pages=S2-6|pmid=19553632|url=http://www.jaoa.osteopathic.org/content/109/6_suppl_2/S2.full.pdf|accessdate=6 October 2014}}</ref>
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| Fewer than 10 percent of people younger than 60 develop postherpetic neuralgia after a bout of herpes zoster, while about 40 percent of people older than 60 do.
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| ==References==
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| {{Reflist}}
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| ==Further reading== | | ==Related pages== |
| *{{cite journal |vauthors=Hempenstall K, Nurmikko TJ, Johnson RW, A'Hern RP, Rice AS |title=Analgesic therapy in postherpetic neuralgia: a quantitative systematic review |journal=PLoS Med. |volume=2 |issue=7 |pages=e164 |year=2005 |pmid=16013891 |doi=10.1371/journal.pmed.0020164 |pmc=1181872}} | | * [[Herpes zoster]] |
| | * [[Varicella-zoster virus]] |
| | * [[Chronic pain]] |
| | * [[Neuropathic pain]] |
| == External links == | | == External links == |
| {{Medical resources | | {{Medical resources |
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| {{Varicella zoster}} | | {{Varicella zoster}} |
| {{Vaccines}} | | {{Vaccines}} |
| {{Headache}} | | {{Headache}} |
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| {{DEFAULTSORT:Postherpetic Neuralgia}} | | {{DEFAULTSORT:Postherpetic Neuralgia}} |
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| [[Category:Virus-related cutaneous conditions]] | | [[Category:Virus-related cutaneous conditions]] |
| [[Category:Neurological disorders]] | | [[Category:Neurological disorders]] |
| [[Category:Pain]] | | [[Category:Pain]] |
| [[Category:Varicella zoster virus-associated diseases]] | | [[Category:Varicella zoster virus-associated diseases]] |
| {{stub}}
| | [[Category:Neurological disorders]] |
| | [[Category:Chronic pain syndromes]] |
| | [[Category:Viral diseases]] |
