Predictive factors and clinical biomarkers for treatment in patients with chronic pain caused by osteoarthritis with a central sensitisation component

Abstract

Aims: The aim of this non-systematic review was to provide a practical guide for clinicians on the evidence for central sensitisation in chronic osteoarthritis (OA) pain and how this pain mechanism can be addressed in terms of clinical diagnosis, investigation and treatment.

Methods: The authors undertook a non-systematic review of the literature including a MEDLINE search (search terms included central sensitisation, osteoarthritis, osteoarthrosis) for relevant and current clinical studies, systematic reviews and narrative reviews. Case reports, letters to the editor and similar literature sources were excluded. Information was organised to allow a pragmatic approach to the discussion of the evidence and generation of practical recommendations.

Results: There is good evidence for a role of central sensitisation in chronic OA pain in a subgroup of patients. Clinically, a central sensitisation component in chronic OA pain can be suspected based on characteristic pain features and non-pain features seen in other conditions involving central sensitisation. However, there are currently no diagnostic inventories for central sensitisation specific to OA. Biomarkers may be helpful for confirming the presence of central sensitisation, especially when there is diagnostic uncertainty. Several non-pharmacological and pharmacological treatments may be effective in OA patients with central sensitisation features. Multimodal therapy may be required to achieve control of symptoms.

Discussion: Clinicians should be aware of central sensitisation in patients with chronic OA pain, especially in patients presenting with severe pain with unusual features.

Figure 1

Neurological changes involved in modulation of ascending and descending pathways in central sensitisation. Cellular and neurological changes involved in central sensitisation include: 1. increased sodium‐channel expression produced by continuous nociceptive stimuli leads to increased glutamate release from nerve endings (‘spontaneous activity’), activating intracellular signalling pathways and consequent phophorylation of NMDA and AMPA; 2. excess action of glutamate on postsynaptic receptors (especially NMDA and AMPA) triggers influx of calcium (intracellular changes); 3. reduced descending inhibition and possibly amplification of descending facilitatory pathways further increases excitability of dorsal horn neurons; 4. involvement of higher centres, especially the PAG and rostroventral medulla. 5‐HT, serotonin; AMPA, α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole proprionic acid; Asp, aspartate; Ca²⁺, calcium; GABA, gamma‐aminobutyric acid; Glu, glutamate; Na⁺, sodium; NE, norepinephrine; NMDA, N‐methyl‐d‐aspartate; PAG, periaqueductal grey matter

Figure 2

Shift in pain stimulus–response curve in central sensitisation (CS)

Figure 3

Diagnostic algorithm for identifying central sensitisation (CS) in patients with osteoarthrosis and related conditions