Age-related change in nociception is an area of significant clinical and scientific interest in the study of pain mechanisms and treatment of pain. One reason for such interest is that in the growing elderly population, pain is often associated with chronic illnesses and is one of the most common reasons prompting the need for medical care. It is unclear whether in addition to increased incidence of chronic illness, age-related physiologic changes on nociception contribute to the increased prevalence of pain in the elderly. Another reason to study age-related changes in nociception is that when pain occurs at younger ages it can lead to long-term changes in pain perception, processing, and development. Therefore, a better understanding of age-specific mechanisms of nociception would enable the development and delivery of age-appropriate therapy. Age-related physiologic changes, such as changes in myelin, in biochemistry of sensory neurons, and nerve fiber density are known to occur. While the impact of age-related physiologic changes on transmission, processing, and perception of pain is incompletely understood, these age-related changes could certainly affect nociception. With regard to sex, it is well know that it impacts on the perception of noxious stimuli. Some studies have shown that in humans, analgesic requirement after surgery are greater in females compared to males. Women have lower response threshold to thermal stimulus compared to males. Therefore in order to properly treat pain, we have to further understand the impact of sex on nociception as well. In humans and animals, few studies have evaluated the effect of aging on Aa (pressure sensation), Aa (well-localized sharp pain), and C (diffuse burning pain) sensory nerve fibers and none has followed animals through the aging process. We are investigating the effects of aging on pain thresholds of Aa, Aa, and C fibers in female and male mice. Using our model of nociception we are measuring current vocalization threshold. We developed this novel assay to evaluate pain thresholds using electrical stimulus of increasing intensity at 5 Hz to stimulate C, 250 Hz to stimulate Aa, and 2000 Hz to stimulate Aa nerve fibers. We define vocalization as the pain-avoiding behavior to electrical stimuli, and measured current vocalization threshold in mice starting at an early age and longitudinally through their life span or 104 weeks. We showed that with the aging process, female mice have a U-shaped response to electrical stimulus. Additional studies are being conducted to further define the mechanism of this pattern of response to electrical stimulus.