PREVENTION OF POST-HERPETIC NEURALGIA

*A. Pasqualucci (1), V. Pasqualucci (2), V. De Angelis (3), V. Marzocchi (4),
A. Brunelli (1), L. Vetrugno (1), M. Lugano (1), L. De Paoli (1)
(1)Department of Anesthesioloy and Intensive Care, University of Udine, (2)Institute of Anesthesiology, Intensive Care and Pain Clinic, University of Perugia, (3)Division of Medical Oncology, Hospital of Perugia, Italy and (4)Department of Dermatology, Hospital of Udine

Treatment of herpes zoster (HZ) includes the use of acyclovir with or without steroids. An alternative therapy is the epidural administration of local anesthetics with or without steroids. This trial compared the efficacy of these two treatment regimens in the prevention of postherpetic-neuralgia (PHN).

Methods:
600 adults >55 years of age with a rash of <7 days duration, and severe pain due to HZ, were enrolled and randomized to receive either intravenous acyclovir (10mg/Kg three times daily) for 9 days + prednisolone (60 mg per day with progressive reduction) for 21 days, or 6-12 ml bupivacaine (0.25%) every 6-8 or 12 hours + methylprednisolone 40 mg every 3-4 days by epidural catheter during a period ranging from 7 to 21 days. Efficacy was evaluated at one, three, six and twelve months. PHN was assessed as pain and/or allodynia, and "abnormal sensations" (hypoesthesia, burning, itching, etc.). Statistical analysis was performed based on the intent-to-treat population.

Results:
In the 485 patients who completed the study, the incidence of pain after 1 year was 22.2% (51 patients of 230) after acyclovir + steroids, and 1.6% (4 patients of 255) after epidural analgesia + steroids. The incidence of abnormal sensations was 12.2% (28 patients) after acyclovir + steroids, and 4.3% (11 patients) in group B.

Conclusions:
Epidural administration of local anesthetic and methylprednisolone is significantly more effective in preventing PHN at 12 months compared to intravenous acyclovir and prednisolone. Based on these data and records from the literature, we propose a pathogenetic hypothesis for PHN: abnormal sensations are due to a milder condition resulting in primarily spinal nerve root damage (caused by varicella-zoster virus), while pain and/or allodynia is caused by a more severe infection that results in dorsal horn damage (in addition to damage of spinal nerve root). Once reactivated, Varicella-Zoster-Virus is especially damaging to the dorsal root ganglia, the peripheral nerves, and the nerve endings, the latter resulting in skin rash. The damage may diffuse centrally to the dorsal horn of the spinal cord via the neurons. It is generally thought that 9-12 days is necessary for central lesions to appear. Local anesthetics prevent PHN by blocking axonal transport and hindering axonal and transneuronal spread of the virus (52-56) and perhaps, indirectly, also its replication.

Corresponding Author: Alberto Pasqualucci, MD, Professor of Anesthesiology and Intensive Care, Department of Anesthesiology, Intensive Care and Pain Clinic, University of Udine, Piaz. S.M. della Misericordia 33100 Udine, Italy. E-Mail: A.Pasqualucci@med.uniud.it