Cold Pain Threshold Identifies a Subgroup of Individuals With Knee Osteoarthritis That Present With Multimodality Hyperalgesia and Elevated Pain Levels

Abstract

Objectives: Cold hyperalgesia has been established as an important marker of pain severity in a number of conditions. This study aimed to establish the extent to which patients with knee osteoarthritis (OA) demonstrate widespread cold, heat, and pressure hyperalgesia. OA participants with widespread cold hyperalgesia were compared with the remaining OA cohort to determine whether they could be distinguished in terms of hyperalgesia, pain report, pain quality, and physical function.

Methods: A total of 80 participants with knee OA and 40 matched healthy, pain-free controls participated. OA participants completed a washout of their usual medication. Quantitative sensory testing was completed at 3 sites using standard methods. Cold pain threshold (CPT) and heat pain thresholds (HPT) were tested using a Peltier thermode and pressure pain thresholds (PPT) using a digital algometer. All participants completed the short-form health survey questionnaire and OA participants completed the PainDETECT, Western Ontario and McMaster Universities Osteoarthritis Index of the Knee (WOMAC), and pain quality assessment scale questionnaires.

Results: OA participants demonstrated widespread cold hyperalgesia (P<0.0001), had lower PPT at the index knee (P<0.0001) compared with controls and reported decreased physical health on the SF-36 (P=0.01). The OA subcohort with high global CPT (≥12.25°C) exhibited multimodality sensitization compared with the remaining OA cohort (PPT P<0.0001; CPT P<0.0001; HPT P=0.021 index knee). This group also reported increased pain, decreased function, and more features of neuropathic pain.

Discussion: This study identified a specific subgroup of patients with knee OA who exhibited widespread, multimodality hyperalgesia, more pain, more features of neuropathic pain, and greater functional impairment. Identification of patients with this pain phenotype may permit more targeted and effective pain management.

Figures

FIGURE 1

PPT at each of the 3 test sites. There was a significant difference in PPT between the OA and control groups at the index knee (A). There was a significant difference in PPT between the low CPT and high CPT groups at all sites (A–C) and there was a significant difference between the high CPT and PFC PPT measures at the index knee and the contralateral knee (A, B). CPT indicates cold pain thresholds; ECRB, extensor carpi radialis brevis; OA, osteoarthritis; PPT, pressure pain thresholds; PFC, pain-free control group.

FIGURE 2

Percentages of OA participants with test values >1 Z-score higher or <95% confidence interval of the mean value for the control group. Values that indicate hyperalgesia are presented as positive scores. Values that indicate hypoesthesia are presented as negative scores. CDT indicates cold detection thresholds; CPT, cold pain threshold; ECRB, extensor carpi radialis brevis; HPT, heat pain thresholds; OA, osteoarthritis; QST, quantitative sensory testing; PPT, pressure pain thresholds; WDT, warm detection threshold.

FIGURE 3

CDT at each of the 3 test sites. There was a significant difference in CDT between the OA and groups at the index knee and the contralateral knee (A, B). There was also a significant difference in CDT between the high and low CPT groups at all sites (A–C). CDT indicates cold detection thresholds; CPT, cold pain thresholds; ECRB, extensor carpi radialis brevis; OA, osteoarthritis; PFC, pain-free control.

FIGURE 4

CPT at each of the 3 test sites. There was a significant difference in CPT between the OA and control groups at all sites (A–C). There was also a significant difference in CPT between the low CPT and high CPT groups at all sites (A–C) and there was a significant difference between the high CPT and control group CPT measures at all sites (A–C). CPT indicates cold pain thresholds; ECRB, extensor carpi radialis brevis; OA, osteoarthritis; PFC, pain-free control.

FIGURE 5

WDT at each of the 3 test sites. There was a significant difference in WDT between the high CPT group and the control group at the contralateral knee (B). There was also a significant difference in WDT between the OA and control groups at all sites (A–C). CPT indicates cold pain thresholds; ECRB, extensor carpi radialis brevis; OA, osteoarthritis; WDT, warm detection thresholds; PFC, pain-free control.

FIGURE 6

HPT at each of the 3 test sites. There was a significant difference in HPT between the low CPT and high CPT groups at all sites (A–C). CPT indicates cold pain thresholds; ECRB, extensor carpi radialis brevis; HPT, heat pain thresholds; OA, osteoarthritis; PFC, pain-free control.

FIGURE 7

Comparison between low and high CPT groups for scores obtained for the WOMAC, PainDETECT, and PQAS (mean±SD) questionnaires. CPT indicates cold pain thresholds; PQAS, pain quality assessment scale; WOMAC, Western Ontario and McMaster Universities questionnaires.