Testosterone Attenuates Post Herpetic Neuralgia, in Part, by Conversion to Estradiol

Abstract

Herpes zoster (HZ) or Shingles is often followed by Post Herpetic Neuralgia (PHN). PHN is a chronic pain condition usually occurring a few months after the visible symptoms of HZ subside. Although Testosterone can affect pain responses, the role of testosterone in PHNs is unknown. Testosterone is converted into estrogen in certain areas including the thalamus of the brain by the enzyme aromatase. We tested our hypothesis that testosterone conversion to estrogen in thalamus attenuates HZ induced pain.

Male Sprague-Dawley rats were divided into control and virus groups receiving whisker pad injections of either MeWo cells or MeWo cells containing varicella Zoster Virus (VZV), respectively. Virus injections (100 µl) were in the left whisker pad and contained either 60,000 pfu of virus or control. Virus and control groups were further divided in two drug groups receiving the aromatase inhibitor letrozole or the vehicle dimethyl sulfoxide (DMSO). Drug was given either locally or systemically. Guide cannulas were placed in the thalamic area for a portion of the rats using stereotaxic coordinates for local administration of drug. The conversion of testosterone into estrogen is selectively inhibited using Letrozole. The motivational and affective aspect of nociception was measured using Place Escape Avoidance Paradigm (PEAP) assay. Measurements were completed once a week for three weeks.

Data obtained were statistically analyzed and demonstrated that virus injection significantly increased the nociceptive response compared to the control. This nociceptive response was significantly increased after administration of Letrozole. In conclusion, testosterone reduces the VZV associated nociceptive response, in part, due to conversion into estrogen in the thalamic region.