(373) Testosterone protect against development of chronic widespread fatigue-induced muscle pain

Abstract

Chronic widespread pain conditions such as fibromyalgia are more common in women than men. We discovered previously that female mice develop bilateral, more severe and longer duration of hyperalgesia than male mice in a model of fatigue-induced muscle pain. We hypnotized that gonadal hormones might related to the development of hyperalgesia, but ovariectomy had no effect on the development of hyperalgesia in the model. The object of this study was to determine if testosterone protect against development of widespread fatigue-induced muscle pain. C57BL6/J mice (n=49) were used in this study. For inducing muscle hyperalgesia, we combined the localized muscle fatigue with two sub-threshold muscle insults (20μl normal saline (pH 5.0) into the gastrocnemius muscle 5 days apart) and muscle fatigue contractions (6 minutes electrically-induced isometric contractions ), neither of which produced muscle hyperalgesia when given alone. Hyperalgesia was assessed by pinching the belly of the muscle with force-sensitive tweezers and was measured before and up to 6 weeks after induction. Male mice were orchiectomized (Orchi) 2 weeks before induction of the model, and compared to sham, and to female mice. Orchidectomized mice and females developed bilateral hyperalgesia 6 days after induction of the model that persists for at least 6 weeks. In comparison, intact males only develop hyperalgesia unilaterally and for only 2 weeks. 6. Replacement of testosterone (Add dose here) in Orchi-male mice protected the animals from developing long-lasting bilateral hyperalgesia with a similar short-duration and unilateral hyperalgesia to intact male mice. Treatment of female mice with testosterone (add dose here) prevented the bilateral hyperalgesia and resulted in a shorter duration of hyperalgesia and were significantly different from female mice treated with vehicle. These results suggest that testosterone protects male and female mice from developing long-lasting widespread mechanical hyperalgesia in a mouse model of chronic muscle pain.