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Peripheral and Central Sensitization of Pain in Individuals With Hand Osteoarthritis and Associations With Self-Reported Pain Severity.

ABSTRACT: OBJECTIVE:Pain sensitization, an important osteoarthritis (OA) pain mechanism, has not been substantially investigated in patients with hand OA. It is unknown how peripheral and central sensitization are related to self-reported hand pain. METHODS:Individuals with verified hand OA in the Nor-Hand study underwent quantitative sensory testing of pressure pain thresholds (PPTs) locally (painful and nonpainful finger joints) and remotely (wrist, trapezius, and tibialis anterior muscles), and testing of temporal summation (TS), a manifestation of central sensitization. We examined cross-sectional associations of PPT tertiles and TS with hand pain using the Numerical Rating Scale (NRS) (range 0-10) and the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) pain subscale (range 0-20). Linear regression models were adjusted for demographics, psychosocial factors, and radiographic severity. RESULTS:This study included 282 participants (88% female) with a median age of 61 years (interquartile range [IQR] 57-66). Participants with the lowest PPTs in their finger joints and in most remote locations reported higher NRS pain values, compared to patients with the highest PPTs, with adjusted β values ranging from 0.6 (95% confidence interval [95% CI] 0.0, 1.2) to 0.9 (95% CI 0.3, 1.5). The 118 participants (42%) with TS reported higher mean ± SD NRS pain values compared to those without TS (4.1 ± 2.4 versus 3.1 ± 1.7; adjusted β = 0.6 [95% CI 0.2, 1.1]). Neither PPTs nor the presence of TS were associated with AUSCAN pain. CONCLUSION:Central sensitization was common in patients with hand OA. Lower local and widespread PPTs and the presence of TS were associated with higher hand pain intensity, even after adjustment for demographics, psychosocial factors, and radiographic severity. Sensitization may therefore represent a possible treatment target.

SUBMITTER: Steen Pettersen P

PROVIDER: S-EPMC6594897 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Osteoarthritis (OA) of the joint is a prevalent disease accompanied by chronic, debilitating pain. Recent clinical evidence has demonstrated that central sensitization contributes to OA pain. An improved understanding of how OA joint pathology impacts upon the central processing of pain is crucial for the identification of novel analgesic targets/new therapeutic strategies. Inhibitory cannabinoid 2 (CB2) receptors attenuate peripheral immune cell function and modulate central neuro-immune responses in models of neurodegeneration. Systemic administration of the CB2 receptor agonist JWH133 attenuated OA-induced pain behaviour, and the changes in circulating pro- and anti-inflammatory cytokines exhibited in this model. Electrophysiological studies revealed that spinal administration of JWH133 inhibited noxious-evoked responses of spinal neurones in the model of OA pain, but not in control rats, indicating a novel spinal role of this target. We further demonstrate dynamic changes in spinal CB2 receptor mRNA and protein expression in an OA pain model. The expression of CB2 receptor protein by both neurones and microglia in the spinal cord was significantly increased in the model of OA. Hallmarks of central sensitization, significant spinal astrogliosis and increases in activity of metalloproteases MMP-2 and MMP-9 in the spinal cord were evident in the model of OA pain. Systemic administration of JWH133 attenuated these markers of central sensitization, providing a neurobiological basis for analgesic effects of the CB2 receptor in this model of OA pain. Analysis of human spinal cord revealed a negative correlation between spinal cord CB2 receptor mRNA and macroscopic knee chondropathy. These data provide new clinically relevant evidence that joint damage and spinal CB2 receptor expression are correlated combined with converging pre-clinical evidence that activation of CB2 receptors inhibits central sensitization and its contribution to the manifestation of chronic OA pain. These findings suggest that targeting CB2 receptors may have therapeutic potential for treating OA pain.

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Peripheral and Central Sensitization of Pain in Individuals With Hand Osteoarthritis and Associations With Self-Reported Pain Severity.

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