Indian Journal of Pain

REVIEW ARTICLE
Year
: 2013  |  Volume : 27  |  Issue : 1  |  Page : 12--21

Post-herpetic neuralgia: A review of current management strategies


Saru Singh1, Ruchi Gupta1, Sukhdeep Kaur1, Jasleen Kaur2,  
1 Department of Anesthesia, SGRDIMSR, Amritsar, Punjab, India
2 Department of Dermatology, SGRDIMSR, Amritsar, Punjab, India

Correspondence Address:
Ruchi Gupta
314-Ranjit Avenue, Amritsar - 143 001, Punjab
India

Abstract

Post herpetic neuralgia (PHN) is a chronic neuropathic pain in the region of the herpes zoster (HZ) rash, persisting after the cutaneous lesions have healed. Despite numerous treatment advances, many patients remain refractory to the current therapies and continue to have pain, physical and psychological distress. In this review, we will discuss the current strategies for prevention and management of this disease, as also the insight into the future probabilities.



How to cite this article:
Singh S, Gupta R, Kaur S, Kaur J. Post-herpetic neuralgia: A review of current management strategies.Indian J Pain 2013;27:12-21


How to cite this URL:
Singh S, Gupta R, Kaur S, Kaur J. Post-herpetic neuralgia: A review of current management strategies. Indian J Pain [serial online] 2013 [cited 2019 Jun 17 ];27:12-21
Available from: http://www.indianjpain.org/text.asp?2013/27/1/12/114857


Full Text

 Introduction



Post herpetic neuralgia (PHN) is one of the most resistant chronic pain problems, commonly affecting elderly patients. It presents as a pain that persists after the resolution of the rash caused by herpes zoster (HZ). Although a variety of definitions of PHN have been used by clinicians and investigators, the results of recent studies suggest that the pain associated with herpes zoster has three phases: An acute herpetic neuralgia, where the pain that accompanies the rash lasts up to 30 days after the onset of rash; subacute herpetic neuralgia that lasts for 30 - 120 days after the onset of rash; and post-herpetic neuralgia, where the pain persists beyond 120 days after the onset of rash. [1] The duration of PHN is highly variable and about 50% of the patients recover within a year of onset of pain. [2]

The pain of PHN usually follows the typical dermatomal distribution of the rash caused by herpes zoster. Unilateral thoracic dermatomes and the trigeminal nerve, especially the ophthalmic branch, are most frequently affected. The pain is typically described as a lancinating or electric shock-like sensation. Apart from this, patchy allodynia, hyperesthesia, and hypoesthesia can present to varying degrees in the affected region.

These spontaneous pains, particularly the allodynia, can be disabling and debilitating leading to depression, social isolation, and increased health care utilization.

Pathophysiology

Varicella zoster virus is a highly contagious double stranded DNA virus of the herpes family. Primary varicella manifests commonly as chickenpox in a non-immune or incompletely immune person. During the primary infection, the virus gains entry into the sensory dorsal root ganglia. Reactivation of the virus occurs following depression of cell-mediated immunity and in advance-aged patients. The reactivated virus replicates and migrates down the sensory nerve leading to the dermatomal distribution of pain. The associated inflammation in the peripheral nerves leads to demyelination, wallerian degeneration, and fibrosis. Thus, as a result, uninhibited and amplified activity in unmyelinated primary afferents leads to pain associated with post-herpetic neuralgia. Research has tried to delineate subtypes of post herpetic neuralgia based on the type of neuronal damage, so that appropriate therapeutic protocols can be laid accordingly. [3]

Rowbotham et al.[4] quantified the sensory presentations and proposed three subtypes based on his research.

The irritable nociceptive group, with mechanical allodynia and normal or hyperalgesic thermal sensationThe central reorganization group with mechanical allodynia and thermal sensory deficitsThe deafferentation group with ongoing pain, without allodynia, and profound sensory loss.

Also, it was found that almost 50% of the patients fell under subtype 2 and the rest were of subtype 1 and 3 in equal proportions. Furthermore, the involvement of the peripheral cutaneous nociceptors was more prevalent early in the disease and the central nervous system (CNS) mechanisms were seen to be involved after about one year. Although the pathophysiology of post-herpetic neuralgia still needs further research, identification of these subtypes is a promising approach to aid proper treatment of such patients. [4]

Prevention of Post Herpetic Neuralgia

About 40 - 50% of the patients suffer from pain despite the use of a multitude of presently available therapies. Therefore, identification of high-risk groups, factors for zoster incidence, and treating acute herpes infection become more important goals. In the recent research, older age, acute pain of severe intensity during herpes zoster, and greater rash severity have been identified, by independent groups of investigators, as the risk factors for PHN. The neural damage in these patients is seen to be severe, which therefore, should be prevented, by starting the therapy early using antiviral agents, corticosteroids and tricyclic antidepressants, paravertebral nerve blocks, [5] sympathetic nerve blocks, [6] and so on [Table 1].{Table 1}

Treatment of Post-Herpetic Neuralgia

A definite treatment protocol is yet to be suggested for patients of PHN, as the efficacy of the proposed treatments is difficult to evaluate. Small sample sizes, difficulty in assigning control groups, ambiguous outcome parameters, and a natural history of resolution of the PHN over a period of time are the main factors that affect the outcome. The initial choice of therapy should be guided by the patient's comorbidities, adverse effects of drugs, and patient preference. A commonly used protocol involves the use of gabapentin and a 5% lidocaine patch as first-line treatments and opioids and Tricyclic antidepressants (TCAs) as second-line treatments for PHN [Figure 1]. [1] {Figure 1}

Pharmacological treatment

Calcium Channel modulators

Gabapentin and Pregabalin are the two gabapentinoids that selectively bind to the α2δ subunit protein of voltage-gated calcium channels in various regions of the brain and superficial dorsal horn of the spinal cord, leading to inhibition of neurotransmitter release.

Gabapentin, a second-generation anticonvulsant, has been seen to provide significant benefits when compared with the placebo, in two large controlled clinical trials involving PHN. [7],[8] In these trials, treatment with gabapentin at daily doses of 1800 - 3600 mg was associated with a statistically significant reduction in the daily pain ratings as well as improvement in sleep, mood, and quality of life.

Evaluation of pregabalin in a randomized, placebo-controlled trial for the treatment of post-herpetic neuralgia and in central neuropathic pain has been found to be safe and efficacious in relieving pain. Sleep interference and associated greater global improvement was there as compared to the placebo. [9]

Both gabapentin and pregabalin are usually well-tolerated. The most common adverse effects include somnolence, dizziness, and peripheral edema. Doses need to be adjusted based on pain relief and renal function [Table 2].{Table 2}

Opioids

The efficacy of opioids in patients with PHN was first demonstrated in a double-blind study comparing intravenously administered morphine with the placebo. [10] Another double-blind, placebo-controlled, randomized trial for the treatment of PHN demonstrated statistically significant benefits with regard to pain, disability, and allodynia, when 60 mg / day of controlled release oxycodone was used. [11] In yet another study, controlled-release morphine titrated to a maximum dosage of 240 mg per day, provided statistically significant benefits with regard to pain and sleep, but not physical functioning and mood. [12]

Opioid therapy is initiated using a short-acting medication such as oxycodone alone or in combination with nonsteroidal anti-inflammatory drugs (NSAIDS) at dosages equianalgesic to the oral administration of morphine sulfate. After one to two weeks of treatment, the patient's total daily dosage of a short-acting opioid analgesic is then converted to an equianalgesic daily dosage of one of the long-acting opioid analgesics, such as, controlled-release morphine, controlled-release oxycodone, transdermal fentanyl, levorphanol, or methadone hydrochloride [Table 2]. Limited access to short-acting medication for breakthrough pain may be added. Conversion of the patient's treatment regimen from short-acting to long-acting medication requires considerable dosage adjustment for one to two weeks. Once the patient is receiving a stable dosage of a long-acting medication, four to six weeks of trial should be given to assess both pain and function. Pain reduction without improvement in function indicates a need to consider modifying the treatment and careful evaluation by a pain specialist.

The most common side effects of opioid analgesic therapy are constipation, sedation, abuse potential, and nausea. In elderly patients treated with opioid analgesics, cognitive impairment and problems with mobility can also occur.

Although opioids are effective, intensive monitoring and the adverse effects associated with them directed further research in favor of tramadol. The use of sustained release tramadol in post-herpetic neuralgia was evaluated by Boureau F et al.[13] in a randomized, double-blind, placebo-controlled trial, and the percentage of pain relief over the sixth week was found to be significantly higher in the tramadol group than in the placebo group. Thus, it is now being used as an add-on drug for the treatment of post-herpetic neuralgia.

Tricyclic Antidepressants

Amitriptyline is clinically the most widely used TCA for the treatment of PHN, because it has been the most extensively studied TCA for PHN. Nortriptyline and Desipramine hydrochloride have fewer adverse effects and are generally better tolerated than amitriptyline, especially in the elderly.

Randomized, double-blind trials comparing two different treatments for patients with PHN have supported this fact that nortriptyline is equivalent in efficacy to amitriptyline, but is better tolerated. [14],[15] Side effects include dry mouth, constipation, sweating, disturbed sleep, and drowsiness, and also should be used cautiously in elderly patients with cardiovascular (CVS) disease and autonomic neuropathy. To decrease the side effects, all TCAs should be initiated at low dosages (10 - 25 mg in a single dose taken at bedtime) and should then be slowly titrated, as tolerated [Table 2].

Topical agents

Local applications have an edge over systemic analgesics, as they have a potential to decrease pain without significant side effects. These preparations are effective when patients have thermal and mechanical allodynia.

Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is a highly selective agonist for the transient receptor potential vanilloid 1 receptor (TRPV1). The initial effect of capsaicin is the activation of the TRPV1-expressing cutaneous nociceptors, which result in pungency and erythema due to the release of vasoactive neuropeptides. Following capsaicin exposure, cutaneous nociceptors become less sensitive to a variety of stimuli and these later-stage effects of capsaicin are frequently referred to as 'desensitization'. Capsaicin-induced alterations in cutaneous nociceptors are reversible and it has been reported and observed that normal function (the detection of noxious sensations) returns within weeks in healthy volunteers. Three different concentrations of this drug have been studied and used.

Capsaicin cream (8%) -it is available as NGX-4010 or Qutenza. The efficacy of a single 60-minute application to the affected locations has been shown in controlled clinical trials conducted in patients with PHN. Pain reduction was observed as early as week one and was maintained throughout the 12-week study period. Lynn R Webster studied twenty-four patients with PHN and found that a single 60-minute application of NGX-4010 was well-tolerated after pre-treatment with lidocaine 2.5% / prilocaine 2.5% cream for 60 minutes. Capsaicin at 8% concentration has been shown to be effective when used alone or when used in combination with oral drugs for PHN. [16]Capsaicin cream (0.075%) -Bernstein JE et al. and Watson CPN in their double blind studies using local application of 0.075% capsaicin in a cream base found it to be effective. [17],[18] It must be applied to the affected area three-to-five times daily.Capsaicin (0.025%) -Several studies in the last century had looked at a lower concentration of capsaicin (0.025%) and found it also to be effective, although two or more weeks of treatment may be required to get the full benefit of the cream. An average decrease of approximately 15% of the magnitude of pain was observed with this preparation.

Lidocaine patch 5%

Treatment with the lidocaine patch 5% consists of the application of a maximum of three patches per day for a maximum of 12 hours, applied directly to the area of maximal PHN-associated pain and allodynia. In double blind, vehicle-controlled, randomized trials, Rowbotham MC et al. and Galer BS approved a lidocaine 5% patch for treatment of PHN. [19],[20] These studies concluded that patients with allodynia obtained significant relief and the side effects were only mild skin reactions in the form of erythema and rash. However, a Cochrane review published in 2007, concluded that this evidence is insufficient to recommend topical lidocaine as first-line therapy in post-herpetic neuralgia with allodynia. [21] Furthermore, in 2009, another recent interim analysis from an open-label, two-stage adaptive, randomized, controlled trial by Baron R et al. found that 5% lidocaine medicated plaster treatment was associated with similar levels of analgesia in patients with PHN, but substantially fewer frequent adverse events than pregabalin. [22] Thus, because of its proven efficacy and safety profile, the lidocaine patch 5% is still being used as a first-line therapy for the treatment of the neuropathic pain [Table 3]. Another patch (EMLA) containing both lidocaine and prilocaine can also be used. Future research may further help in justifying the use of these agents in post-herpetic neuralgia.{Table 3}

Topical Nonsteroidal Anti-Inflammatory Drugs

Topical Aspirin -Topical aspirin, known chemically as triethanolamine salicylate, has also been used by various authors. Preparation of the aspirin / diethyl ether mixture was studied in two double blind controlled trials by De Benedittis G et al. These two studies show good-to-excellent results in 93 and 87% of the AHN patients; and, 65 and 82% of the PHN patients, respectively. [23],[24] However, this evidence is weak, to recommend the use of this preparation for patients suffering from post-herpetic neuralgia [Table 3].

Other Preparations-

Skin Coolants - Ethyl chloride (Chloroethane) and fluori-methane are chemicals that cool the blood vessels in the skin. Sprays that contain these chemicals are not anesthetics, but they are used to inactivate the sensitive areas. To use the spray, the patient must be in a comfortable position. The spray bottle is held upside-down, about 12 - 18 inches from the targeted area. The face must be covered if the spray is being used near the head. [25] Although these sprays may provide temporary relief, there is no long term benefit associated with their use.Menthol-containing Preparations -Topical drugs containing menthol may be helpful due to local action, but there is no evidence to support their use. [25]

Systemic Therapy

N-methyl-D-aspartate Antagonist -These drugs have been proposed to act by blocking the interaction of excitatory nociceptive input with NMDA receptors in a spinal dorsal horn (peripheral sensitization). These drugs also prevent allodynia, persistent pain, as well as tolerance to opioids (central sensitization).

Ketamine has been used as IV and subcutaneous in a small number of trials showing that all elements of PHN pain are reduced or abolished. However, significant side effects such as fatigue, dizziness, mood changes, infusion site problems, and so on, have limited the parenteral utility of ketamine. On the other hand, oral ketamine was reported to be efficacious for pain relief in patients with PHN, without side effects. [26]

Other NMDA receptors antagonists like dextromethorphan and mementine can be used IV, but the efficacy of these agents have not been proved yet. [26]

Intravenous lidocaine -A double-blind RCT comparing intravenous lidocaine to saline showed reduction in PHN pain and allodynia with lidocaine. This finding is the basis for the use of oral mexiletine, to achieve systemic sodium channel blockade and reduction of PHN pain in patients who respond to IV lidocaine. [26] Another sodium channel blocker flecainide is also under trial, but the efficacy of all these drugs has yet to be proved.

Interventional Therapies

Some patients with PHN may have persistent pain despite pharmacological, topical, psychological, and physical therapies. These cases of refractory PHN may be managed using epidural injections, paravertebral nerve blocks, sympathetic nerve blocks, intrathecal steroids, and pulsed radiofrequency, as discussed below [Figure 1].

Epidural injection of a local anesthetic either intermittently or via continuous catheter is effective in reducing pain severity and duration during acute herpes zoster outbreaks. There is little evidence to suggest that epidural injections alter the course of established PHN aside from providing transient relief [Table 3]. [26] Paravertebral nerve block has been used by Naja ZM to relieve pain in PHN using repetitive injections of local anesthetic mixture (Bupivacaine 0.5% 19 ml and clonidine 150 μg ml -1 ) every 48 hours for three weeks, using a catheter inserted at the T 2 -T 3 level. There were no complications, the patient remained pain-free for over an eight-month follow-up period, but evidence to support this treatment is weak [Table 3]. [27]The use of intraspinal agents such as opioids and local anesthetics has had some success, especially when adding local anesthetics to the level of the segmental block. Further use of intraspinal clonidine and another drug, SNX 111 is under trial for the treatment of chronic post-herpetic neuralgia. Intrathecal methylprednisolone has shown that it is effective in the preliminary study, but is not approved by the US Food and Drug Administration since it carries the risk of arachnoiditis and other neurological complications [Table 3]. [28] Radiofrequency ablation using the heat lesioning protocol has been reported in literature for deafferentation pain resulting from post-herpetic neuralgia. Heat lesioning is performed with temperatures of 67°C or higher. Common side effects of heat lesioning include dysesthesias, hypesthesias, proprioceptive losses, and paresis. [29] Pulsed radiofrequency lesioning (PRF) is a safe, nondestructive, neuroablative modality, which obviates the complications of heat lesioning. It helps in pain modulation and can be performed multiple times, as needed. Although the precise mode of action is unknown it has been postulated to modulate the pain processing mechanisms at the dorsal root ganglion, dorsal horn, and molecular levels. Lesioning of the dorsal root ganglion (DRG) using pulsed radiofrequency (PRF) has shown pain reduction in patients with severe post-herpetic neuralgia. In an open, nonrandomized study, 49 patients with PHN, refractory to conservative therapy, were subject to PRF, performed thrice, adjacent to the DRG of the corresponding levels at 42°C for 120 seconds, under the fluoroscopy. There was excellent pain relief (about 55%) at four weeks, with the effect lasting till the 12-week follow-up. [30] In a case report, Kuthuru MR et al. selected a 77-year-old male with post-herpetic neuralgia affecting the left eye and forehead, refractory to pharmacological and topical treatment for PRF lesioning at the frontal nerve and supraorbital nerve after diagnostic nerve blocks. The patient had 80% relief after second lesioning, with the relief lasting for about one to two weeks, and was continued with the treatment using a combination of medications, local anesthetic / steroid injections and pulsed RF. [29] However, further research is required to strengthen the evidence and determine the optimal electrical parameters of PRF. Endoscopic Transthoracic Sympathectomy (ETS) has been described by Isao Matsumoto et al. in a case of a 72-year-old woman who developed intractable PHN of the chest. In this method a single resectoscope is used to transect the sympathetic ganglions using cauterization, and it was found to be safe, accurate, cosmetically excellent, and associated with very little postoperative pain, because of minimal invasion. The author concluded that although ETS cannot be recommended for all cases of PHN, it could be a useful method for treating patients with PHN that is resistant to conventional therapies by the blocking the sympathetic excitation. [31]Implantable Devices -A pump is implanted underneath the skin and a tube is tunneled to the intrathecal space. Medications can be delivered from the pump directly to the spinal cord including morphine, hydromorphone, or Bupivacaine. This modality can be used for resistant and severe cases of post-herpetic neuralgia.

Surgical Ablative Therapies

Patients refractory to all the treatments have been reported to have undergone procedures such as neurolytic nerve blocks, peripheral neurectomy, dorsal root entry zone lesions, sympathectomy, trans-spinal ganglionectomy, prefrontal lobotomy, and the like. Onofrio BM et al. found that a long-term successs rate of 30% was found with dorsal rhizotomy to treat post-herpetic neuralgia. [32],[33] However, there are no proper studies to support other ablative procedures. Thus, due to the absence of supportive evidence and a potential for adverse effects, surgical ablative therapies are not preferred. [26]

Neuromodulation / Spinal Cord Stimulation

Peripheral Nerve Stimulation and Peripheral Nerve Field Stimulation -Peripheral Nerve Stimulation (PNS) generally implies implantation of a stimulating electrode either directly on a particular nerve via surgical visualization or perhaps more commonly the percutaneous placement of a stimulating electrode in close proximity to a particular peripheral nerve. In Peripheral Nerve Field Stimulation (PNFS), stimulating electrodes are percutaneously placed in the epicenter of the painful areas themselves, without respect to a particular named nerve's location. In both the techniques, the underlying concept remains the same: Using electrical stimulation peripherally to provide paresthesias in painful areas, leading to pain relief. The exact mechanism by which these approaches render pain relief is incompletely understood. A widely held hypothesis is that pain relief may be explained by the 'gate-control' theory, originally described by Melzack and Wall, in their landmark article published in 1965. The gate of pain transmission is opened by the activation of nociceptive-specific neurons, while putative inhibitory neurotransmitters are thought to be released during large myelinated nerve fiber stimulation.

Peripheral neuromodulation has been described by various authors for the management of intractable PHN, which is refractory to the commonly used regimes. After successful trial stimulation, a permanent stimulator is placed and patient medications are tapered off following onset of the effect. Kouroukli I, Neofytos D et al. reported percutaneous peripheral nerve stimulation for treatment of intractable PHN in two geriatric cases, with a two- and ten-year duration of pain, respectively. These patients were effectively treated with the implantation of two octapolar leads in the lateral thoracic region. [34] In another case report, Upadhyay SP and Kouroukli I et al. managed supraorbital PHN, where after trial stimulation, a permanent stimulator was placed and the patient had excellent pain relief eight weeks post stimulation without any side effect. [35]

Although a limited number of patients have been studied to date, the existing data suggest that peripheral nerve stimulation may offer an alternative treatment option for intractable pain associated with PHN, especially in the elderly, where treatment options are limited because of the existing comorbidities.

Spinal Cord Stimulator -This device contains a receiver implanted underneath the skin and the electrodes placed in the epidural space and directly on top of the spinal cord. Patients feel a buzzing or comfortable humming sensation when the stimulator is activated. The electrical stimulation of the posterior spinal cord activates supraspinal and spinal inhibitory pain mechanisms. This leads to the release of gamma-aminobutyric acid (GABA) and the activation of the GABA-B and adenosine A-1 receptors, as also inhibition of the release of excitatory amino acids glutamate and aspartate in the dorsal horn, thus suppressing neuronal pain transmission and sympathetic outflow. Spinal cord stimulation (SCS) may re-establish the impaired balance between the excitatory and inhibitory mechanisms, provided neuronal death or complete deafferentation does not result from PHN. [36] The studies on the use of SCS for the treatment of post-herpetic neuralgia have provided mixed results. Harke et at. (2002), in a prospective case series of 28 patients reported that 82% of the patients with PHN derived long-term relief for more than two years. [37] On the other hand, Kumar et al. (1996), noted that only 38% patients were relieved of pain after stimulation; and, a follow up after seven years further reduced this number to only 25%. [38] Furthermore, Joon Oh Kim et al. reported a 75-year-old man who had undergone dorsal root ganglionectomy for post herpetic neuralgia in the thoracic dermatomes. Although this patient was relieved from allodynia after the surgery, he continued to experience deep excruciating cramping pain. This pain improved to a tolerable state with the help of spinal cord stimulation, and thus, the authors recommend it as a useful option. [39]

Although the level of evidence for SCS treatment of PHN is not high, it may offer a worthwhile option in the treatment of pharmacological non-responders with anatomically intact neural pathways, provided the patients accept an invasive approach [Table 3]. Moreover, in cases of unbearable HZ pain, this approach can also provide supportive benefit [Figure 1].

Other Therapies

They include, acupuncture, transcutaneous electrical nerve stimulation (TENS), physical therapy, psychological intervention, Gunns I/M stimulation, vincristine iontophoresis, and current perception threshold analysis, for evaluating the symptoms of PHN and determining the appropriate strategy for such patients. There are no randomized controlled trials showing that their worth is superior to placebo.

 Comprehensive Treatment Approach



Sequential and combination treatments, with first- and second-line medications, can be used to enhance pain relief and achieve improvement in the quality-of-life of affected individuals [Figure 1]. An ideal treatment would involve 'rational polypharmacy' based on the understanding of the pathophysiological mechanisms of herpes, and such an approach to the treatment of post-herpetic neuralgia may become possible, as the understanding of the mechanisms of pain increase. However, there is no data regarding the additive or synergistic benefits of combination treatment, and it is not known which patients are most likely to benefit from what medication combinations. Moreover, the disadvantages of such combinations include an increased risk of side effects due to the simultaneous use of a multiple class of drugs and the difficulty in identifying which medication caused that adverse effect. [1]

Apart from drugs, various non-pharmacological therapies are also added to enhance the pain relief by controlling the physiological and psychological components of pain. These therapies can be in the form of TENS, behavioral therapies and psychological counseling. Although there are no proper randomized controlled trials to support them, the lack of any significant side effects and cost-effectiveness has been supporting them since decades.

 Recent Advances



Newer Drugs

There is evidence that the newer antidepressants, such as, venlafaxine, bupropion, and paroxetine have analgesic properties. The overall effectiveness of these drugs is probably less than the tricyclic antidepressants, but the likelihood of troubling side effects is substantially less. Patients who are predisposed to tricyclic side effects, or who have not been able to tolerate these drugs, may be good candidates for trials of the newer antidepressants.Another drug, DM-1796, an investigational, extended release, once-daily tablet formulation of gabapentin, has been designed to reduce the dosing frequency and have a low incidence of side effects. The New Drug Application (NDA) for DM-1796 was accepted by the US Food and Drug Administration (FDA) for the management of PHN. The NDA follows the completion of a randomized, double-blind, placebo-controlled Phase 3 study of 452 PHN patients. The study demonstrated that 1800 mg of DM-1796 dosed once daily, achieved a statistically significant reduction in the average daily pain score associated with PHN versus placebo using the numerical Likert pain scale. [40] The most common side effects observed in patients receiving DM-1796 were dizziness (11.3% compared to 1.7% for placebo) and somnolence (5.4% compared to 3.0% for placebo). Yet another drug ATx08-001, which is an orally-available PPAR-gamma agonist, is being tested, particularly for the pain associated with PHN, by Aestus Therapeutics. (February 2011). This drug, which has been examined in Phase I and Phase II studies comprising over 800 patients, has characteristics of unprecedented safety and toxicology profile. [41] The research on this drug is being directed to justify it as first-in-class treatment for neuropathic pain.

Vaccination --The OKA Strain of a live attenuated virus vaccine has been proved safe, immunogenic, and highly protective against severe varicella in healthy children, adults, and immunocompromised patients. It may also be used to boost the Varicella zoster virus (VZV) immunity in the elderly, thus decreasing the incidence of occurrence in them. Although the vaccination may be efficacious and safe for preventing herpes zoster, there is insufficient direct evidence from specialized trials to prove the efficacy of the vaccine for preventing and reducing the incidence of post-herpetic neuralgia in adults aged 60 years or older. [42]

Future

Control and prevention of herpes zoster incidence using effective vaccination and thus eradication of the disease from the community is the key.Prevention of post-herpetic neuralgia in patients afflicted with herpes zoster should be our primary aim, as the onset of neuralgia debilitates and distresses the patients for years together. Identification of subtypes based on the pathophysiology of post-herpetic neuralgia holds a key to the development of mechanism-specific therapies to tailor treatment to individual patients.Ongoing and future clinical research is expected to define the efficacy of all the above discussed therapies and outline a treatment protocol that may help us to make a comprehensive approach tailored to each patient.There is also a need to study the role of invasive pain management techniques in the prevention of PHN as well as treatment of refractory PHN.

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