CNS Symptoms as Predictors of Future Chronic Primary Pain

Date Posted:

January 2026

Study Title:

The Number of Central Nervous System-Driven Symptoms Predicts Subsequent Chronic Primary Pain: Evidence from UK Biobank

Authors:

Kelleher E, Kaplan CM, Kheirabadi D et al.

 

The International Classification of Diseases 11th Revision describes two major categories of pain: chronic primary pain and chronic secondary pain. Chronic secondary pain refers to conditions in which pain is a symptom of another disease, such as fracture, nerve injury, or soft-tissue damage supported by imaging and clinical findings. In contrast, chronic primary pain is defined as a disease, rather than a consequence of another condition. Examples include fibromyalgia (chronic widespread pain), chronic primary low back pain, endometriosis, irritable bowel syndrome, and temporomandibular disorders. Collectively, these conditions are termed ‘Chronic Overlapping Pain Conditions’ (COPC) and are believed to be primarily driven by altered nociceptive processing within the CNS causing hypersensitivity and spreading pain. These functional changes in CNS processing are believed to be the cause of symptoms in nociplastic pain conditions.

Patients with primary pain disorders frequently report CNS-mediated symptoms such as fatigue, insomnia, dyscognition (ex. “fibro-fog”), and mood disturbance. Generally, these conditions fall into two symptom clusters: generalized sensory sensitivity (ex. diffuse pain with mild pressure) and S.P.A.C.E (sleep, pain, affect, cognitive symptoms, and energy/fatigue). It remains unclear whether these CNS-related symptoms precede the onset of chronic primary pain or whether their presence increases the risk of developing such conditions later in life.

This study aimed to examine the relationship between the burden of three S.P.A.C.E symptoms, namely sleep disturbance, mood disturbance, and cognitive difficulty, and the future development of chronic primary pain. The authors hypothesized that adults without chronic pain who exhibit a higher burden of S.P.A.C.E symptoms are at increased risk of subsequently developing a primary pain disorder.