Grant: Project Grant

Most living beings have a biological "clock" that regulates critical aspects of life, including sleep, feeding, temperature control, and hormones. These cycles usually last 24 hours and are called circadian rhythms (from the latin "circa diem", or about a day). These circadian rhythms are key to nervous and immune cell function - for example, immune cells are recruited to tissues and organs at specific times of day, and clinical outcomes in various disease-states are known to be dependent on time-of-day. Recent work from our multidisciplinary team has uncovered an unexpected role for circadian rhythms in both humans and mice: regulation of chronic pain and its associated neuroinflammation. We now seek to extend these findings by i) identifying rhythmic changes in pain and immune cell function in a cohort of people with chronic low back pain (which can be of neuropathic, inflammatory or mixed origin); ii) create a nationwide study to identify how circadian rhythms affect pain and associated biopsychosocial outcomes; and iii) identify the contribution of circadian rhythms to immune cell function using preclinical models of chronic neuropathic and inflammatory pain. Few effective pain treatment options are currently available, severely impacting quality of life. Most patients fail to respond to first-line treatments and instead turn to opioids, which carry severe side effects and can lead to abuse, underscoring the need for new therapies. Dissecting circadian rhythms in chronic neuropathic and inflammatory pain may help uncover new psychosocial, cellular, and molecular strategies for treating chronic pain across various conditions.