Circadian Rhythmicity of Chronic Low Back Pain: A Cross-Sectional Study

Abstract

Chronic low back pain (CLBP) is defined as pain occurring between the ribcage and buttocks, maladaptively persisting for longer than 3 months. Unfortunately, current treatments are often associated with several negative effects, such as addiction, and may decrease in effectiveness with long term use. Novel therapeutic strategies are therefore needed to help manage chronic pain and improve quality of life. Despite the high prevalence of CLBP, the underlying biological mechanism has not been fully elucidated as differing aetiologies cause varying inflammatory responses between individuals. CLBP is thought to arise from a combination of neuropathic and inflammatory origins, where neuropathic pain follows damage to the nervous system and inflammatory pain is caused by immune infiltration to the site of injury. Interestingly, opposing rhythmic patterns of pain intensity has been identified; whereby an evening peak in pain intensity among individuals with CLBP and identify a potential underlying biological mechanism at the cellular and molecular levels. Electronic pain diaries submitted at 8:00, 14:00, and 20:00 over a 7-day period reveal four distinct patterns in CLBP pain intensity. Observed Constant (Low) and (High) pain groups differ only in mean intensity and remain constant throughout the day, while the Mixed and Circadian group pain scores are highly variable, with an evening peak in pain intensity specific to the Circadian cluster. Several associations were identified between pain intensity, fatigue, and depressive mood. Furthermore, those with Constant (High) CLBP had the lowest mental quality of life and reported greater fatigue, depressive mood, anxiety, and use of opioids and antidepressants relative to all other pain patterns. Lastly, clusters did not differ significantly in either cellular or molecular levels regarding immune cell content or core clock and inflammatory mediator gene expression. While daily variations in pain are evident across CLBP, more work is needed to elucidate underlying biological mechanisms at the protein level. This investigation should inspire the use of circadian concepts to drive novel therapeutic discovery and guide time-specific treatment delivery.