Show notes
Summary In this episode of the Pain Exam Podcast, Dr. David Rosenblum provides a comprehensive review of herpes zoster and postherpetic neuralgia (PHN), focusing on pathophysiology, diagnosis, and treatment options. Dr. Rosenblum explains that postherpetic neuralgia affects approximately 25% of patients with acute herpes zoster, causing debilitating unilateral chronic pain in one or more dermatomes. He discusses the three phases of herpes zoster: acute (up to 30 days), subacute (up to 3 months), and postherpetic neuralgia (pain continuing beyond 3 months). Dr. Rosenblum identifies risk factors for developing PHN, including older age, female sex, immunosuppression, prodromal pain, severe rash, and greater acute pain severity. He details the pathophysiology involving peripheral and central sensitization, and explains different phenotypes of PHN that can guide treatment approaches. For treatment, Dr. Rosenblum reviews various options including antiviral medications (which should be started within 72 hours of onset), corticosteroids, opioids, antidepressants (particularly tricyclics and SNRIs), antiepileptics (gabapentin and pregabalin), topical agents (lidocaine and capsaicin), and interventional procedures such as epidural injections and pulsed radiofrequency. He emphasizes that prevention through vaccination with Shingrix is highly effective, with 97% effectiveness in preventing herpes zoster in patients 50-69 years old and 89% effectiveness in those over 70. Dr. Rosenblum mentions that he's currently treating a patient with trigeminal postherpetic neuralgia and is considering a topical sphenopalatine ganglion block as a minimally invasive intervention before attempting more invasive procedures. Chapters Introduction to the Pain Exam Podcast and Topic Overview Dr. David Rosenblum introduces the Pain Exam Podcast, mentioning that it covers painful disorders, alternative treatments, and practice management. He explains that this episode focuses on herpes zoster and postherpetic neuralgia as board preparation for fellows starting their programs, with ABA boards coming up in September. Dr. Rosenblum notes that he's not only preparing listeners for boards but also seeking the latest information to help treat his own patients with this notoriously difficult disease. Upcoming Conferences and Educational Opportunities Dr. Rosenblum announces several upcoming conferences including Aspen in July, Pain Week in September, and events with NYSIP and the Latin American Pain Society. He mentions he'll be teaching ultrasound and regenerative medicine at these events. Dr. Rosenblum invites listeners to sign up at nrappain.org to access a community discussing regenerative medicine, ultrasound-guided pain medicine, regional anesthesia, and board preparation. He also offers ultrasound training in New York and elsewhere, with upcoming sessions in Manhattan on July 12th and October 4th, plus private shadowing opportunities. Overview of Postherpetic Neuralgia Dr. Rosenblum defines postherpetic neuralgia as typically a unilateral chronic pain in one or more dermatomes after acute herpes zoster infection. He states that the incidence of acute herpes zoster ranges between 3-5 patients per thousand person-years, and one in four patients with acute herpes zoster-related pain will transition into postherpetic neuralgia. Dr. Rosenblum emphasizes that while this condition won't kill patients, it can be extremely debilitating and significantly reduce quality of life. Treatment Options Overview Dr. Rosenblum reviews treatment options according to the WHO pain ladder, including tricyclics like nortriptyline and antiepileptic drugs such as gabapentin. He explains that if pain is not significantly reduced, interventional treatments like epidural injections with local anesthetics and corticosteroids or pulsed radiofrequency of the dorsal root ganglion are options. For postherpetic neuralgia specifically, Dr. Rosenblum notes that preferred treatments include transdermal capsaicin, lidocaine, or oral drugs such as antidepressants or antiepileptics. Phases of Herpes Zoster and Definitions Dr. Rosenblum outlines the three phases during herpes zoster reactivation: acute herpes zoster-related pain (lasting maximum 30 days), subacute herpes zoster-related pain (pain after healing of vesicles but disappearing within 3 months), and postherpetic neuralgia (typically defined as pain continuing after 3 months). He mentions that acute herpes zoster pain often begins with prodromal pain starting a few days before the appearance of the rash. Incidence and Risk Factors Dr. Rosenblum states that the incidence of herpes zoster ranges between 3-5 patients per 1,000 person-years, with approximately 5-30% of cases leading to postherpetic neuralgia. He identifies risk factors including older age, female sex, immunosuppression, prodromal pain, severe rash, and greater acute pain severity. Dr. Rosenblum describes the clinical manifestations as a mosaic of somatosensory symptoms including burning, deep aching pain, tingling, itching, stabbing, often associated with tactile and cold allodynia. Impact on Quality of Life Dr. Rosenblum emphasizes that postherpetic neuralgia can be debilitating, impacting both physical and emotional functioning and causing decreased quality of life. He notes that it leads to fatigue, insomnia, depression, anorexia, anxiety, and emotional distress. Dr. Rosenblum stresses the importance of exploring methods for prevention of postherpetic neuralgia and optimizing pain treatment for both subacute herpes zoster-related pain and postherpetic neuralgia. Literature Review and Pathophysiology Dr. Rosenblum mentions that he's discussing a literature review from 2024 that updates previous practical guidelines published in 2011. He explains the pathophysiology of postherpetic neuralgia, which involves sensitization of peripheral and sensory nerves from damage. Dr. Rosenblum describes how inflammatory mediators reduce the stimulus threshold of nociceptors and increase responsiveness, resulting in pathological spontaneous discharges, lower thresholds for thermal and mechanical stimuli, and hyperalgesia. Central Sensitization and Nerve Damage Dr. Rosenblum explains that central sensitization results from peripheral nociceptor hyperactivity leading to plastic changes in the central nervous system, involving amplification of pain signals and reduced inhibition. He describes how nerve damage in postherpetic neuralgia patients results from neuronal death due to severe inflammatory stimuli or secondary to neuronal swelling. Dr. Rosenblum notes that motor defects occur in 0.05% of patients with herpes zoster, observed as abdominal pseudohernias or motor weakness of limbs limited to the affected myotome. Different Phenotypes and Classification Dr. Rosenblum discusses different phenotypes of postherpetic neuralgia and how phenotyping can determine treatment. He explains that there are several ways to classify the phenotypes, with one categorizing patients into three subtypes: sensory loss (most common), thermal gain, and thermal loss with mechanical gain. Dr. Rosenblum describes the mechanistic categorization, including the irritable nociceptive phenotype characterized by preserved sensation, profound dynamic mechanical allodynia, reduced pressure pain threshold, and relief with local anesthetic infiltration. Deafferentation Phenotype Dr. Rosenblum explains that a deafferentation phenotype may arise from destruction of neurons by the virus in the dorsal root ganglion. This phenotype is characterized by sensory loss, including thermal and vibratory sensation without prominent thermal allodynia. He notes that mechanical allodynia can occur secondary to A-beta fibers activating spinothalamic pathways (known as phenotypic switches), along with pressure hyperalgesia and temporal summation suggesting central sensitization. Dr. Rosenblum mentions that in one study, this phenotype was present in 10.8% of individuals, and for those with deafferentation pain, gabapentinoids, antidepressants, and neuromodulatory therapies like repetitive transcranial magnetic stimulation may be beneficial. Diagnosis and Physical Examination Dr. Rosenblum discusses the diagnosis of herpes zoster and postherpetic neuralgia, emphasizing the importance of physical examination. He explains that diagnosis is based on the rash, redness, papules, and vesicles in the painful dermatomes, with healing vesicles showing crust formation. Dr. Rosenblum notes that the rash is generally unilateral and does not cross the midline of the body. In postherpetic neuralgia patients, he mentions that scarring, hyper or hypopigmentation is often visible, with allodynia present in 45-75% of affected patients. Sensory Testing and Assessment Dr. Rosenblum explains that in patients with postherpetic neuralgia, a mosaic of somatosensory alterations can occur, manifesting as hyperalgesia, allodynia, and sensory loss. These can be quantified by quantitative sensory testing, which assesses somatosensory functions, dermal detection thresholds for perception of cold, warmth, and paradoxical heat sensations. He notes that testing can provide clues regarding underlying mechanisms of pain, impaired conditioned pain modulation, temporal summation suggesting central sensitization, and information about the type of nerve damage and surviving afferent neurons. Prevention Through Vaccination Dr. Rosenblum discusses prevention of acute herpes zoster through vaccination, noting that the risk increases with reduced immunity. He highlights studies evaluating Shingrix, a vaccine for herpes zoster, which showed 97% effectiveness in preventing herpes zoster in patients 50-69 years old with healthy immune systems and 89% effectiveness in patients over 70. Dr. Rosenblum states that Shingrix is 89-91% effective in preventing postherpetic neuralgia development in patients with healthy immune systems and 68-91% effective in those with weakened or underlying conditions. Treatment Objectives Dr. Rosenblum outlines the treatment objectives for herpes zoster and postherpetic neuralgia. For acute herpes zoster, objectives include relieving pain, reducing severity and duration of pain, accelerating recovery of epidermal defects, and preventing secondary infections. For postherpetic neuralgia, the objectives are pain alleviation and improved quality of life. Dr. Rosenblum lists available treatments including psychotherapy, opiates, antidepressants, antiepileptics, NMDA antagonists, topical agents, and interventional treatments such as epidurals, pulsed radiofrequency, nerve blocks, and spinal cord stimulation. Antiviral Medications Dr. Rosenblum emphasizes that antiviral drugs should be started within 72 hours of clinical onset, mentioning famciclovir, valacyclovir, and acyclovir. He notes there is no evidence for effectiveness after 72 hours in patients with uncomplicated herpes zoster. Dr. Rosenblum provides dosing information: for immunocompetent patients, famciclovir 500mg and valacyclovir 1000mg three times daily for seven days; for immunocompromised patients, famciclovir 1000mg three times daily for 10 days, while acyclovir should be given IV in the immunocompromised. Benefits of Antiviral Therapy Dr. Rosenblum explains that antiviral medication accelerates the disappearance of vesicles and crusts, promotes healing of skin lesions, and prevents new lesions from forming. By inhibiting viral replication, he notes that antiviral therapy likely reduces nerve damage, resulting in reduced incidence of postherpetic neuralgia, and should be started as soon as possible. Corticosteroids and Opioids Dr. Rosenblum discusses the use of corticosteroids, noting that when added to antiviral medications, they may reduce the severity of acute herpes zoster-related pain, though increased healing of skin lesions was not observed in one study. He mentions that a Cochrane review found oral corticosteroids ineffective in preventing postherpetic neuralgia. Regarding opioids, Dr. Rosenblum states they are commonly used alongside antivirals for controlling acute herpes zoster pain, with tramadol having a number needed to treat (NNT) of 4.7 and strong opioids having an NNT of 4.3 for 50% pain reduction. Methadone and Antidepressants Dr. Rosenblum discusses methadone as an NMDA receptor antagonist used in acute and chronic pain management, though he notes there are no randomized controlled trials determining its efficacy in acute herpes zoster pain or postherpetic neuralgia. He explains that methadone can modulate pain stimuli by inhibiting the uptake of norepinephrine and serotonin, resulting in decreased development of hyperalgesia and opioid tolerance, but has side effects including constipation, nausea, sedation, and QT prolongation that can trigger torsades de pointes. Dr. Rosenblum identifies antidepressants as first-line therapy for postherpetic neuralgia, including tricyclics and SNRIs, with tricyclics having an NNT of 3 and SNRIs an NNT of 6.4 for 50% pain reduction. Antiepileptics and Pharmacological Treatment Summary Dr. Rosenblum discusses antiepileptics like gabapentin and pregabalin for postherpetic neuralgia. He cites two trials measuring gabapentin's effect, concluding it was effective compared to placebo with a pooled NNT of 4.4, while pregabalin had an NNT of 4.9. Dr. Rosenblum summarizes that pharmacological treatment is well established for subacute herpes zoster pain, though new high-quality evidence has been lacking since the last update in 2011. Topical Agents Dr. Rosenblum discusses local anesthetic topical agents including lidocaine and capsaicin creams and patches. He notes that 8% capsaicin provided significant pain reduction during 2-8 weeks, while 5% lidocaine patches provided moderate pain relief after eight weeks of treatment. Dr. Rosenblum also mentions acute herpes zoster intracutaneous injections, citing a study where single intracutaneous injection with methylprednisolone combined with ropivacaine versus saline alone showed significant difference in VAS score at 1 and 4 weeks post-intervention favoring the intervention group. Intracutaneous Injections Dr. Rosenblum discusses the effect of repetitive intracutaneous injections with ropivacaine and methylprednisolone every 48 hours for one week. He cites a randomized control trial comparing antivirals plus analgesics to antivirals plus analgesics and repeat injections, finding the intervention group had significantly shorter duration of pain, lower VAS scores, and lower incidence of postherpetic neuralgia (6.4% vs 28% at 3 months). Dr. Rosenblum notes that a potential side effect of cutaneous methylprednisolone injection is fat atrophy, though this wasn't reported in the study. Summary of Local Anesthetics Dr. Rosenblum summarizes that there are no new studies reporting the efficacy of capsaicin 8% for postherpetic neuralgia, but it remains widely used in clinical practice and is approved in several countries. He notes that lidocaine patches can reduce pain intensity in patients with postherpetic neuralgia but may be more beneficial in patients with allodynia. Dr. Rosenblum adds that intracutaneous injections may be helpful for short periods, while repetitive injections with local anesthetics may reduce VAS scores for up to six months but can cause subcutaneous fat atrophy. Interventional Treatments: Epidural and Paravertebral Injections Dr. Rosenblum discusses interventional treatments, noting that previous guidelines found epidural injection with corticosteroids and local anesthetic as add-on therapy superior to standard care alone for up to one month in managing acute herpes zoster pain. He mentions a randomized controlled trial showing no difference between interlaminar and transforaminal epidural steroid injections for up to three months after the procedure. Dr. Rosenblum adds that previous guidelines reported high-quality evidence that p…
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