Patients on Prophylactics Maintain Pain Thresholds Over Year Study

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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Differences in sensory detection and pain thresholds were found in hemophilia patients taking prophylactics, compared to healthy individuals, and these differences did not change over the course of a one-year follow-up study.

These findings indicate that “under prophylactic treatment, the existing difference in the pain profile between [people with hemophilia] and controls at baseline [study entry] does not appear to be a progressive process within 1 year,” the researchers wrote.

The study, “Changes in pain profile of patients with haemophilia during 1-year follow-up,” was published in the journal Haemophilia.

Hemophilia is caused by deficiencies in specific blood clotting factors. A lack of these factors increases the number of bleeding episodes and the likelihood of spontaneous bleeding in joints, most often the elbows, knees, and ankles.

Joint bleeding is often accompanied by pain, commonly assessed by visual analog scales or pain questionnaires.

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Previously, researchers at the University of Wuppertal in Germany showed that pain thresholds in knee and elbow joints are altered in people with hemophilia using quantitative sensory testing (QST) — a semi-objective method to assess sensory nerve function that examines a broad range of different sensations, including pain, touch, hot, cold, and vibration.

Now, the team has explored the changes in knee and ankle joint pain, as well as on an unaffected site (the dominant hand), over a one-year period using QST and compared the findings with healthy individuals.

The study enrolled 24 patients ranging in age from 34 to 70 years (mean age 52 years), of whom 19 had severe hemophilia A (lacking factor VIII) and three had severe hemophilia B (lacking factor IX). Two patients with moderate hemophilia were included, one with hemophilia A and one with hemophilia B.

Eligible patients had at least one painful knee or ankle joint. All severe cases were treated with preventive (prophylactic) factor replacement therapies, which provide functional factor VIII and IX proteins.

Compared to controls, people with hemophilia had significantly higher joint scores at study entry (baseline) and at follow-up, as measured by the physical joint examination instrument, with higher scores indicating more impaired joint status. Likewise, subjective pain and pain intensity scores were also significantly higher in all examined joints at both time points in hemophilia patients.

At all three sites examined — joints in the knee, ankle, and dominant hand — hemophilia participants showed significant differences compared to controls in terms of sensory detection thresholds and pain thresholds.

In the knee joints, mechanical pain sensitivity in patients was significantly higher than in controls, as measured by pinpricks along with tactile stimuli using a brush, cotton swab, and cotton ball. There was a trend towards increased pain sensitivity to the stimuli in the ankles, and no difference between the two groups at the dominant unaffected hands.

Participants with hemophilia also experienced significantly reduced mechanical pain thresholds, measured in milliNewtons (mN), in the knees, ankles, and hands using a device in which force was continuously increased until a painful sensation was felt.

After one year, there were significant changes in the profiles of hemophilia patients and controls, with larger changes seen in the patient group.

In the knee joints of patients, there was a significant increase in mechanical detection thresholds using filaments applied in decreasing force intensity until they became undetected, rising from 6.8 mN at baseline to 9.8 mN after one year. Likewise, detection thresholds increased from 13.9 to 19.4 mN in the patients’ ankles, and from 1.7 to 3.8 mN in their dominant hands.

The same was seen for the knees (4.7 vs. 6.8 mN after one year), ankles (12.0 to 13.7 mN), and hands (1.9 to 2.6 mN) of the controls, but these changes were smaller compared to those with hemophilia. Also, no relevant differences were seen over the year for thermal (hot and cold) detection thresholds.

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Finally, plotting QST measurements over one year showed similar patterns between patients and controls.

“Using the QST data, we were able to demonstrate for the first time a pain profile of the ankle joints, and also the course of pain at knee joints, ankle joints, and an unaffected reference over 1 year in [patients with hemophilia] using semi-objective pain measurements,” the researchers wrote.

“The QST profile between [patients] and controls does not seem to deteriorate further over the course of a year under a prophylactic treatment regimen and may only be affected by age-related changes,” they added. “Therefore, it would be beneficial to investigate how the pain sensation in [patients with hemophilia] develops in countries where no prophylactic therapy is available.”