BRUSSELS – Patients with severe or long-standing knee osteoarthritis can develop central sensitization and as a result may have heightened pain sensitivity, based on findings from a study of 920 people.
The development of central sensitization “may have implications for the management of osteoarthritis-related pain,” Dr. Tuhina Neogi said at the meeting.
Dr. Tuhina Neogi
“The hypothesis is that constant nerve stimulation [in patients with knee osteoarthritis] from mechanical and inflammatory stimuli can lead to alterations in the nervous system” that result in central sensitization and lead to changes in central nervous system signaling and possibly increased pain sensitivity in the affected knee.
Finding that central sensitization occurs in some patients with osteoarthritis means that “pain management options may change, with therapies targeting the neurologic processes of central sensitization,” Dr. Neogi said in an interview. Even though the knee pain in these patients “is probably related to structures and biomechanical targets,” the new findings “indicate that there are also neurologic targets for pain management” in osteoarthritis patients who show signs of central sensitization.
“There is active research on treatments that can target these neurologic processes; this is not unique to knee osteoarthritis,” said Dr. Neogi, a rheumatologist and epidemiologist at Boston University. Other conditions that produce chronic pain and cause central sensitization lead to situations where “the pain is no longer related to the pathology.” Examples include postherpetic neuralgia and diabetic neuropathy. Some drugs may be able to relieve this sort of pain, such as duloxetine (Cymbalta), a serotonin norepinephrine reuptake inhibitor.
Dr. Neogi’s study involved patients enrolled in the Multicenter Osteoarthritis Study (MOST), a study with more than 3,000 participants aged 50-79 years at entry. Starting in 2003, the MOST investigators enrolled both patients with knee osteoarthritis and additional people at high risk for later developing knee osteoarthritis at two U.S. sites. Her study focused on a subgroup of 920 MOST participants who underwent an assessment of central sensitization using a temporal summation test 60 months after they entered the study. Temporal summation is an augmented pain response following repetitive mechanical stimuli that indicates the presence of central sensitization.
The temporal summation test involved touching the subject with a nonpainful, 60-g monofilament once every 30 seconds to see if this produced new or increased pain. The researchers performed the filament test on both patellae and one wrist.
The average age of the 920 people who underwent the temporal summation examination was 68, two-thirds were women, and 41% did not have knee osteoarthritis.
The analysis used a within-person comparison design, in which the researchers compared the central sensitization of the unaffected knee of each patient with osteoarthritis with that of their affected knee. This design helped eliminate unidentified confounding factors that could produce different responses to pain between study participants.
The analysis showed that the knees of patients with the most severe forms of osteoarthritis, with Kellgren-Lawrence (KL) grades of 3 or 4 or knee replacement surgery, had a statistically significant, nearly threefold higher rate of central sensitization than did knees without osteoarthritis. Knees with a KL grade of 2 had a statistically significant, 60% higher prevalence of central sensitization than did knees with a KL grade of 1, Dr. Neogi reported at the congress, sponsored by the Osteoarthritis Research Society International.
The duration of osteoarthritis also affected the prevalence of central sensitization at the 60-month follow-up visit. Knees affected by osteoarthritis at entry to the study had a significant, 2.6-fold increased prevalence of central sensitization compared with knees without osteoarthritis at entry. The researchers saw no significant increase in central sensitization at 60 months in knees that first showed osteoarthritis at the 30-month follow-up examination.
The within-person analysis played a critical role in finding the relationship between osteoarthritis severity and duration, and the development of central sensitization. A comparison of measurements between participants showed no significant link between disease severity or duration and central sensitization, despite adjustment for age, sex, and body mass index. Dr. Neogi said she attributed this to the inability of a between-individual analysis to fully account for genetic, psychosocial, and cultural factors that can affect pain perception.