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Degenerative conditions in low back and neck pain are generally not considered the main cause of symptoms. Recently, identification of relevant anti-nociceptive and pro-nociceptive mechanisms has been considered important for guiding management and treatment of musculoskeletal pain. Objectives of the present explorative study were to investigate anti-nociceptive and pro-nociceptive pain mechanisms, pain intensity, and psychological distress in patients with chronic low back pain (LBP, N=18), neck pain (N=17), sciatica (N=18), or cervicobrachialgia (N=17). Cuff algometry was performed on the non-painful lower leg to assess pressure pain threshold (cPPT), pressure pain tolerance (cPTT), temporal summation of pain (TSP: increase in pain scores to ten repeated stimulations), and conditioned pain modulation (CPM: increase in cPPT during cuff pain conditioning on the contralateral leg). Heat detection (HDT) and heat pain thresholds (HPT) at the non-painful hand were recorded. Clinical pain intensity (numerical rating scale; NRS) and psychological distress were assessed by questionnaires. Compared with localized neck pain patients, cervicobrachialgia patients demonstrated increased NRS pain scores and reduced HPT and cPTT, reduced CPM, and higher scores of psychological distress (P<0.05). Compared with localized neck pain patients, LBP patients demonstrated increased NRS pain scores and reduced cPTT, and higher scores of psychological distress (P<0.05). TSP was increased in patients with sciatica and cervicobrachialgia compared with patients with localized pain (LBP, neck pain; P<0.05). These findings have clinical implications as different underlying mechanisms may require different treatment strategies as illustrated between the mechanistic differences within localized pain (LBP, neck) and between localized pain and referred pain. Future research should investigate interventions tailored towards these mechanisms.