The objective of this article is to provide evidence-based recommendations for the management of patients with herpes zoster (HZ) that take into account clinical efficacy, adverse effects, impact on quality of life, and costs of treatment. Systematic literature reviews, published randomized clinical trials, existing guidelines, and the authors' clinical and research experience relevant to the management of patients with HZ were reviewed at a consensus meeting. The results of controlled trials and the clinical experience of the authors support the use of acyclovir, brivudin (where available), famciclovir, and valacyclovir as first-line antiviral therapy for the treatment of patients with HZ. Specific recommendations for the use of these medications are provided. In addition, suggestions are made for treatments that, when used in combination with antiviral therapy, may further reduce pain and other complications of HZ.

Smoked cannabis was well tolerated and effectively relieved chronic neuropathic pain from HIV-associated sensory neuropathy. The findings are comparable to oral drugs used for chronic neuropathic pain.

Keratinocytes are implicated in sensory transduction and can influence nociception, but whether these contribute to chronic pain is not known. In neurons, voltage-gated sodium channels (Na(v)) are involved in neuropathic pain and are activated by depolarization. Since keratinocytes can also show changes in membrane potential, we used RT-PCR, in situ hybridization, and immunohistochemistry to investigate the expression of sodium channels in these cells. Na(v)1.1, Na(v)1.6, and Na(v)1.8 were localized within keratinocytes in rat epidermis. In addition, sodium channels contribute to the release of ATP from rat keratinocytes in response to increased [K(+)](o), implicating sodium channels in keratinocyte ligand release and nociception. To examine whether keratinocytes may contribute to human pain states, we analyzed sodium channel expression in human skin biopsies from subjects with complex regional pain syndrome Type 1 (CRPS) and post-herpetic neuralgia (PHN) using immunohistochemistry. Control skin exhibited immunolabeling for Na(v)1.5, Na(v)1.6 and Na(v)1.7. In contrast, painful skin from CRPS and PHN subjects displayed Na(v)1.1, Na(v)1.2, and Na(v)1.8 immunolabeling, in addition to substantially increased signal for Na(v)1.5, Na(v)1.6, Na(v)1.7. These observations lead us to propose that pathological increases in keratinocyte sodium channel expression may contribute to pain by increasing epidermal ATP release, resulting in excessive activation of P2X receptors on primary sensory axons. Consistent with this hypothesis, animal models of neuropathic pain exhibit increases in subcutaneous ATP release and activity of primary sensory neurons, and peripheral administration of P2X antagonists has been shown to reduce neuropathic pain in humans.

The functional and morphologic characteristics of isolated subcutaneous resistance vessels (about 170 fitn i.d.) from 15 untreated subjects with essential hypertension and 15 matched controls were examined. The vessels from the hypertensives had a 29% increase in the media-thickness-to-lumendiameter ratio. The maximal force development to noradrenaline (NA) expressed as active pressure (an estimate of the pressure the vessels could have contracted against in vivo) was 30 % higher in vessels from the hypertensives, while active media stress (force per square unit of smooth muscle) and sensitivity to NA was not significantly different. Increased active pressure, as well as unaltered active media stress and sensitivity, was seen for vasopressin, serotonin, angiotensin II, and K + . There was, however, an enhanced leftward shift of the NA sensitivity with cocaine (an inhibitor of the neuronal amine pump) in vessels from the hypertensives [pD 2 ( + cocaine) and pD 2 ( -cocaine) were 0.185 ± 0.053 and 0.040 ± 0.044, hypertensives and normotensives, respectively, p < 0.05] suggesting an abnormality of presynaptic function in essential hypertension. Furthermore, the calcium sensitivity was depressed (pD 2 was 4.197 ± 0.050 and 4.381 ± 0.068, hypertensives and normotensives, respectively, p < 0.05), and the rate of relaxation was faster (p < 0.05) in vessels from hypertensives, suggesting that excitation-contraction coupling might be depressed. The results suggest that the increased pressor response in essential hypertension can, to a large extent, be explained by altered vascular structure, while smooth muscle function is either unchanged or possibly depressed.

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