Postherpetic Neuralgia

Postherpetic Neuralgia

Postherpetic neuralgia is the most common complication of shingles. Inflammation in the nerve can result in continued pain, even after the shingles rash is gone. Among people age 60 years and younger, the risk of PHN three months after the onset of the zoster rash is 1.8%. Herpes zoster is uncommon in persons less than 15 years old. “The key to minimizing shingles and preventing postherpetic neuralgia is to diagnose early and to treat both the virus and the pain very aggressively. There is no other pain quite like this. The pain level varies.

But some people continue to feel pain long after the rash and blisters heal. Side effects and the addictive nature of this class of medications are, however, potential concerns. Journal of Infectious Diseases. As much as 30.7% of people in the US are estimated to suffer from chronic pain. The pain experienced with post-herpetic neuralgia is a type of neuropathic pain, which persist beyond injury resolution and is difficult to treat. This virus is called herpes zoster. The pain can interfere with sleep and activities of daily living.
Postherpetic Neuralgia

Postherpetic neuralgia causes continuing nerve pain that does not go away when the rash clears. However, with age, the body loses its ability to attract enough stem cells to the site of injury. In this regard, stem cell therapy delivers a high concentration of stem cells to the affected area to promote natural healing. A study by Klass et al studied the effect of intravenous syngeneic bone marrow mononuclear cells on a model of rat sciatic nerve injury. The findings revealed a dramatic reduction of pain behaviors in the treated rats. Moreover, mesenchymal stem cells (MSCs) are known to secrete anti-inflammatory factors that modulate pain. A pilot study evaluated the effect of MSCs on patients with knee osteoarthritis, and found a beneficial effect on pain symptoms.

Neuropathic pain is also known to be linked with the loss of GABA-ergic interneurons in the spinal cord. Research from the University of California, San Francisco, transplanted mouse embryonic brain neural precursors into the spinal cord of rats with sciatic nerve injury. Tiny, electrical impulses are sent via a device to these electrodes, which interferes with pain signals and stimulates the production of endorphins (body’s natural pain relievers). The pain may be described as “burning” or “stinging” and is generally unrelenting. To help regenerate nerve tissue in patients with postherpetic neuralgia, some doctors use alternative treatments like Vitamins B6 and B12, folic acid, and Alpha-Lipoic acid. Contact us at R3 Stem Cell Clinics for an evaluation of your neuralgia, and to learn more about regenerative medicine options with stem cell procedures. References Klass M, Gavrikov V, Drury D, Stewart B, Hunter S, Denson DD, Hord A, Csete M: Intravenous mononuclear marrow cells reverse neuropathic pain from experimental mononeuropathy.

Don’t use patches containing lidocaine on your face. Braz JM, Sharif-Naeini R, Vogt D, Kriegstein A, Alvarez-Buylla A, Rubenstien JL, Basbaum AI: Forebrain GABAergic neuron precursors integrate into adult spinal cord and reduce injury-induced neuropathic pain. 3, 2015. Lukovic D, Stojkovic M, Moreno-Manzano V, Bhattacharya SS, Erceg S: Perspectives and future directions of human pluripotent stem cell-based therapies: lessons from Geron’s clinical trial for spinal cord injury. Stem Cells Dev 2014; 23:1-4.

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Postherpetic neuralgia

Postherpetic neuralgia

Postherpetic neuralgia (PHN) is the most common and devastating complication of acute herpes zoster (HZ). Typically, the neuralgia is confined to a dermatomic area of the skin and follows an outbreak of herpes zoster (HZ, commonly known as shingles) in that same dermatomic area. Overview; Presentation; DDx; Workup; Treatment . (Our schedule does include several breaks.)  Different topics will be explored in detail using home-study guideline questions and detailed answers with comments from faculty. During those 4 years, numerous treatments were tried, including systemic opioid analgesics and anticonvulsants, and topical lidocaine and capsaicin, all with unsatisfactory results. There are some sporadically successful experimental treatments, such as rhizotomy (severing or damaging the affected nerve to relieve pain) and TENS (a type of electrical pulse therapy). Neurodestructive procedures are not recommended as they enhance destruction and neuropathic pain.

The damage causes nerves in the affected dermatomic area of the skin to send abnormal electrical signals to the brain. The demographics of trigeminal neuralgia are that it occurs most often in people over the age of 50, although it can occur at any age according to the sources. A key factor in the neural plasticity underlying neuropathic pain is altered gene expression in sensory dorsal root ganglia (DRG) neurons. Gallium has significant anti-inflammatory activity, inhibiting the activation and proliferation of pro-inflammatory T cells. Following nerve damage, NaC channel accumulation causes hyperexcitability, downregulation of the TTX-resistant Nav1.8 (sensory neuron specific, SNS1) channel and upregulation of TTX-sensitive Nav1.3 (brain type III) 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 PHN.

(see also Neuralgia, trigeminal) 350.1. Classes of Drugs: I. If patients do develop postherpetic neuralgia, they are also advised to see their doctor immediately. They may have to work with their doctor and sometimes other specialists such as neurologists to try a variety of treatments before they find something that helps. These findings are not predictive of the PHN clinical course. Viral culture or immunofluorescence staining may be used to differentiate herpes simplex from herpes zoster in cases that are difficult to distinguish clinically. Many, many other types of neuralgias exist.

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. Antiviral agents, such as famciclovir, are given at the onset of attacks of herpes zoster to shorten the clinical course and to help prevent complications such as postherpetic neuralgia. However they have no role to play following the acute attack if postherpetic neuralgia has become established. Analgesics Locally applied topical agents Aspirin mixed into an appropriate solvent such as diethyl ether may reduce pain.[3] Lidocaine skin patches. Multiple sclerosis (MS) is a disease that is caused by the degradation of myelin. III.

Patches containing lidocaine can also be used on the face, taking care to avoid mucus membranes e.g. eyes, nose and mouth. Pain modification therapy Antidepressants. These drugs affect key brain chemicals, including serotonin and norepinephrine, that play a role in both depression and how your body interprets pain. Doctors typically prescribe antidepressants for postherpetic neuralgia in smaller doses than they do for depression. Low dosages of tricyclic antidepressants, including amitriptyline, seem to work best for deep, aching pain. They don’t eliminate the pain, but they may make it easier to tolerate.

Other prescription antidepressants (e.g. venlafaxine, bupropion and selective serotonin reuptake inhibitors) may be off-label used in postherpetic neuralgia and generally prove less effective, although they may be better tolerated than the tricyclics. Anticonvulsants. Postherpetic neuralgia. They have central effects on pain modulation. Medications such as phenytoin (Dilantin, Phenytek), used to treat seizures, also can lessen the pain associated with postherpetic neuralgia. The medications stabilize abnormal electrical activity in the nervous system caused by injured nerves.

Doctors often prescribe another anticonvulsant called carbamazepine (Carbatrol, Tegretol) for sharp, jabbing pain. Newer anticonvulsants, such as gabapentin (Neurontin) and lamotrigine (Lamictal), are generally tolerated better and can help control burning and pain. In some cases, treatment of postherpetic neuralgia brings complete pain relief. But most people still experience some pain, and a few don’t receive any relief. Although some people must live with postherpetic neuralgia the rest of their lives, most people can expect the condition to gradually disappear on its own within five years. High-Concentration Capsaicin Patch Granted Orphan Drug Designation for PHN from:http://www.medscape.com/viewarticle/704117?sssdmh=dm1.489879&src=ddd On June 9, 2009, The FDA approved orphan drug designation for a high-concentration capsaicin dermal patch (Qutenza [formerly NGX-4010], NeurogesX, Inc) for the treatment of pain associated with postherpetic neuralgia (PHN). Relief of pain is possible up to three months with no to minimal[clarification needed] side effects.

Qutenza has been recently[when?] approved by the FDA for general use in PHN. Postherpetic neuralgia affects nerve fibers and skin, causing burning pain that lasts long after the rash and blisters of shingles disappear. In 1995, the Food and Drug Administration (FDA) approved the vaccine to prevent chickenpox. Its effect on PHN 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 chickenpox virus lying dormant in the body and reactivating later as shingles. If shingles could be prevented, postherpetic neuralgia could be completely avoided. Recently, Merck has tested a new vaccine (Zostavax) against shingles.[7] This vaccine is a more potent version of the chickenpox vaccine.

Postherpetic neuralgia
Evidence indicates that the vaccine reduced the incidence of shingles by 51 percent. Additionally, the vaccine reduced the incidence of PHN by two-thirds compared to placebo. However, the vaccine’s protective effects diminished over the three years that most patients were followed.[8] In December 2005, an FDA advisory committee unanimously agreed that the vaccine is safe and effective for persons over 60 years old.[9] This was followed on 26 May 2006 by the FDA formally approving the use of the vaccine for that same age group.[10] Further studies may demonstrate if there is benefit in patients 50–59 years old and if a booster dose is recommended. ^ “CPostherpetic Neuralgia (PHN) Therapeutics – Pipeline Assessment and Market Forecasts to 2017”. http://www.globaldata.com/reportstore/Report.aspx?ID=Postherpetic-Neuralgia-PHN-Therapeutics-Pipeline-Assessment-and-Market-Forecasts-to-2017&ReportType=Industry_Report&coreindustry=Industry_Report&Title=Pharmaceuticals_and_Healthcare. ^ Bowsher, David, MD, ScD, PhD. “Treating shingles with tricyclic antidepressants to lessen the risk of PHN”.

The Center for Shingles and Postherpetic Neuralgia. http://shingles.mgh.harvard.edu/tricyclics.htm. Retrieved 2006-05-11. ^ De Benedittis G, Besana F, Lorenzetti A (1992). “A new topical treatment for acute herpetic neuralgia and post-herpetic neuralgia: the aspirin/diethyl ether mixture. An open-label study plus a double-blind controlled clinical trial”. Pain 48 (3): 383–90.

doi:10.1016/0304-3959(92)90088-S. PMID 1594261. ^ He L, Zhang D, Zhou M, Zhu C (2008). He, Li. ed. “Corticosteroids for preventing postherpetic neuralgia”. Cochrane Database Syst Rev (1): CD005582.

doi:10.1002/14651858.CD005582.pub2. PMID 18254083. ^ Doble S (2008). “Spinal Management of patients with post-herpetic neuralgia”. Nursing Standard 22 (39): 49–56. PMID 18578133. ^ Harke H, Gretenkort P, Ladleif HU, Koester P, Rahman S (2002).

“Spinal cord stimulation in postherpetic neuralgia and in acute herpes zoster pain”. Anesthesia & Analgesia 94 (3): 694–700. doi:10.1097/00000539-200203000-00040. PMID 11867400. ^ Oxman MN, Levin MJ, Johnson GR, et al. (2005). “A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults”.

N. Engl. J. Med. 352 (22): 2271–84. doi:10.1056/NEJMoa051016. PMID 15930418.

^ “Merck Zostavax Shingles Vaccine Decreases In Efficacy Over Three-Year Period, FDA Says”. FDA Advisory Committee. 2005-12-15. http://www.fdaadvisorycommittee.com/FDC/AdvisoryCommittee/Committees/Vaccines+and+Related+Biological+Products/121505_Zostavax/121505_ZostavaxP.htm. Retrieved 2006-06-15. [dead link] ^ “Merck Zostavax Shingles Vaccine Safe and Effective For Adults Over 60, Committee Says”. FDA Advisory Committee.

2005-12-16. Archived from the original on 2006-05-06. http://web.archive.org/web/20060506202436/http://www.fdaadvisorycommittee.com/FDC/AdvisoryCommittee/Committees/Vaccines+and+Related+Biological+Products/121505_Zostavax/121505_ZostavaxR.htm. Retrieved 2006-06-15. ^ “FDA Licenses New Vaccine to Reduce Older Americans’ Risk of Shingles”. United States Food and Drug Administration. 2005-05-26.

http://www.fda.gov/bbs/topics/NEWS/2006/NEW01378.html. Retrieved 2006-06-15. ^ Alper BS, Lewis PR (2000). “Does treatment of acute herpes zoster prevent or shorten postherpetic neuralgia?”. The Journal of family practice 49 (3): 255–64. PMID 10735485. – Commentary at ACPJC ^ Bowsher D (1997).

“The effects of pre-emptive treatment of postherpetic neuralgia with amitriptyline: a randomized, double-blind, placebo-controlled trial”. Journal of pain and symptom management 13 (6): 327–31. doi:10.1016/S0885-3924(97)00077-8. PMID 9204652.

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Postherpetic Neuralgia

Postherpetic Neuralgia

A herpes zoster vaccine (Zostavax®) received US FDA approval in 2006 for use in adults aged 60 years or older [6] and in 2011 was approved for use in those aged ≥50 years [7]. To prevent virus reactivation, a new VZV vaccine (Zostavax, Merck) that boosts cell-mediated immunity to VZV was developed. Studies that focused on the use of corticosteroids for treatment or prevention were eligible for inclusion. Vaccination is recommended as a preventive measure. PHN pain is typically localized, unilateral and chronic, but may be constant, intermittent, spontaneous and/or evoked. Patients and Methods: The study included 17 patients with distressing post herpetic neuralgia. A number of nontraditional analgesic agents have been used in the management of postherpetic neuralgia.

Pain and temperature detection systems are hypersensitive to light mechanical stimulation, leading to severe pain (allodynia). Carbamazepine, like conventional analgesics, is of little or no value. Other patients with PHN may have severe, spontaneous pain without allodynia, possibly secondary to increased spontaneous activity in deafferented central neurons or reorganization of central connections. 5th ed. This input on an abnormal dorsal horn containing deafferented hypersensitive neurons supports the clinical observation that both central and peripheral areas are involved in the production of pain. Acute pain in the early stage of shingles results from the onset of central sensitisation and destructive changes in the dorsal horn [1, 2]. While there is no specific waiting period after having shingles before receiving the zoster shingles vaccine, generally a patient should wait until the shingles rash has resolved before getting vaccinated.

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). 10-21-2010. Although HZ symptoms may be confined to a few sensory dermatomes, pathological changes may be more widespread. Affected ganglia of the spinal or cranial nerve roots are swollen and inflamed with a primarily lymphocytic reaction. Some ganglion cells are swollen while others are degenerated. Incidence of Severe Herpes Zoster Including Postherpetic Neuralgia in Vaccinated and Unvaccinated Cohorts, Overall, and by Age (50-59, 60-69, 70) at Vaccination Time Frame: 10 years Designated as safety issue: No Incidence of Severe Herpes Zoster Including Postherpetic Neuralgia in Vaccinated and Unvaccinated Cohorts by Time since Vaccination Time Frame: 10 years Designated as safety issue: No.

Pathological changes in the brain stem are similar to those in the spinal root and spinal cord. In the months following infection, fibrosis occurs in the ganglia, peripheral nerve, and nerve root. Degeneration occurs in the ipsilateral posterior column. The starting dose was 0.21 J/cm 2 and the dose was increased by one increment every session (as long as there is no adverse effect reported such as persistent erythema, burn, itching). Zostavax was already approved for use in individuals aged 60 years or older. Annually, in the United States, shingles affects approximately 200,000 healthy people aged 50-59 years. Approval was based on a multicenter study, the Zostavax Efficacy and Safety Trial (ZEST).[9] The trial was conducted in the United States and 4 other countries in 22,439 people aged 50-59 years.

Participants were randomized in a 1:1 ratio to receive either Zostavax or placebo. Risk of herpes/herpes zoster during anti-tumor necrosis factor therapy in patients with rheumatoid arthritis. Compared with placebo, Zostavax significantly reduced the risk of developing zoster by approximately 70%. As defining PHN itself is clearly challenging, we decided to apply the less complex form of the definition because it does not influence the choice of treatment and avoids confusion. 3. Clinical Context:  Has demonstrated effectiveness in treatment of chronic pain; by inhibiting reuptake of serotonin and/or norepinephrine by presynaptic neuronal membrane, may increase synaptic concentration in CNS; pharmacodynamic effects such as desensitization of adenyl cyclase and down-regulation of beta-adrenergic receptors and serotonin receptors also appear to play role in its mechanisms of action. Complex group of drugs that have central and peripheral anticholinergic effects as well as sedative effects.
Postherpetic Neuralgia

[Medline]. They block the active reuptake of norepinephrine and serotonin. Clinical Context:  Natural chemical derived from plants of Solanaceae family. By depleting and preventing reaccumulation of substance P in peripheral sensory neurons, may render skin and joints insensitive to pain. Substance P thought to be chemomediator of pain transmission from periphery to CNS. Clinical Context:  Transient receptor potential vanilloid-1 (TRPV1) agonist indicated for neuropathic pain associated with postherpetic neuralgia. TRPV1 is an ion channel–receptor complex expressed on nociceptive skin nerve fibers.

Topical capsaicin causes initial TRPV1 stimulation that may cause pain, followed by pain relief by reduction in TRPV1-expressing nociceptive nerve endings. Five patients dropped out at sessions 2, 4, 7, 10, and 12 due to lack of satisfactory improvement. Clinical Context:  Several recent studies have advocated topical administration of lidocaine as treatment of PHN. Lidocaine gel (5%) in placebo-controlled study showed significant relief in 23 patients studied. Lidocaine tape also decreases severity of pain. Clinical Context:  Approved by FDA for use in PHN. Zosteriform herpes simplex.

Pregabalin binds with high affinity to alpha2-delta subunit of voltage-gaited calcium channels, thereby reducing excitatory neurotransmitters. Regardless of the number of blocks for these cases, the clinical data was used in our final analysis. Oxman MN, Levin MJ, Johnson GR, et al. Peak plasma concentration occurs at one and one half hours after oral intake. Bioavailability is 90%. Famciclovir for the treatment of acute herpes zoster: effects on acute disease and postherpetic neuralgia. Can be taken with or without food.

Clinical Context:  This medication has been approved by the FDA for the treatment of PHN. Has properties common to other anticonvulsants and antineuralgic effects. Exact mechanism of action is not known. Structurally, gabapentin is related to GABA, but it does not interact with GABA receptors. Believed to have a binding site at the alpha 2-delta protein, an auxiliary subunit of voltage-gaited calcium channels. In the rat brain, binding is localized on neuronal dendritic areas. Previous studies have shown important interactions between LCs and cutaneous neuritis.

Clinical Context:  Gabapentin prodrug that provides a longer duration of action compared with gabapentin. Structurally related to neurotransmitter GABA, but has no effect on GABA binding, uptake, or degradation. The mechanism for analgesic activity is unknown. Approved by the FDA for PHN. These agents are used to manage severe muscle spasms and provide sedation in neuralgia. They have central effects on pain modulation. Statistica 10 (StatSoft, Tulsa, USA) software was used for data analysis.

Beers MH, Jones TV, Berkwits M, et al, eds. HZ development decreased 51.3% (P < 0.001) and PHN decreased 66.5% (P < 0.001). In the ZEST trial, the vaccine significantly reduced the risk by 70% in individuals aged 50-59 years.

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