The effect of pregabalin or duloxetine on arthritis pain: a clinical and mechanistic study in people with hand osteoarthritis

Abstract

Osteoarthritis (OA) is the most prevalent arthritis worldwide and is characterized by chronic pain and impaired physical function. We hypothesized that heightened pain in hand OA could be reduced with duloxetine or pregabalin. In this prospective, randomized clinical study, we recruited 65 participants, aged 40-75 years, with a Numerical Rating Scale (NRS) for pain of at least 5. Participants were randomized to one of the following three groups: duloxetine, pregabalin, and placebo. The primary endpoint was the NRS pain score, and the secondary endpoints included the Australian and Canadian Hand Osteoarthritis Index (AUSCAN) pain, stiffness, and function scores and quantitative sensory testing by pain pressure algometry. After 13 weeks, compared to placebo, ANOVA found significant differences between the three groups (P=0.0078). In the intention-to-treat analysis, the pregabalin group showed improvement for NRS pain (P=0.023), AUSCAN pain (P=0.008), and AUSCAN function (P=0.009), but no difference between duloxetine and placebo (P>0.05) was observed. In the per protocol analysis, NRS pain was reduced for pregabalin (P<0.0001) and duloxetine (P=0.029) compared to placebo. We conclude that centrally acting analgesics improve pain outcomes in people with hand arthritis, offering new treatment paradigms for OA pain.

Keywords: duloxetine; hand osteoarthritis; pain; pregabalin; sensitization.

Figure 1

Pain sensitization characteristics of study population. Notes: (A) Data from the DUPRO clinical trial demonstrating reduced pain thresholds globally in the wrist and finger joints in hand OA participants compared to normal age- and sex-matched controls. (B) Graphs demonstrating correlation for PPT in Newton per centimeter squared at baseline with clinical measures for AUSCAN_P, AUSCAN_S, and AUSCAN_F in all groups. Abbreviations: AUSCAN_P, Australian and Canadian Hand Osteoarthritis Index pain; AUSCAN_S, Australian and Canadian Hand Osteoarthritis Index stiffness; AUSCAN_F, Australian and Canadian Hand Osteoarthritis Index function; OA, osteoarthritis; PPT, pain pressure threshold; QST, quantitative sensory testing.

Figure 2

CONSORT flow diagram for the DUloxetine or PRegabalin for Osteoarthritis pain (DUPRO) clinical trial.

Figure 3

Study flow diagram and outcome measures. Abbreviations: AUSCAN, Australian and Canadian Hand Osteoarthritis Index; HADS, Hospital Anxiety and Depression Scale; NRS, Numerical Rating Scale; OA, osteoarthritis.

Figure 4

(A, B) Plots for change in primary outcome measures in all treatment groups (ITT analysis). Abbreviations: AUSCAN, Australian and Canadian Hand Osteoarthritis Index; ITT, intention-to-treat; NRS, Numerical Rating Scale.

Figure 5

CONSORT 2010 checklist of information for the DUloxetine or PRegabalin for Osteoarthritis pain (DUPRO) randomized controlled trial. Note: *Page numbers optional depending on journal requirements. Hopewell S, Clarke M, Moher D, Wager E, Middleton P, Altman DG, et al. CONSORT for reporting randomised trials in journal and conference abstracts. Lancet. 2008;371:281–283.

Figure 5

CONSORT 2010 checklist of information for the DUloxetine or PRegabalin for Osteoarthritis pain (DUPRO) randomized controlled trial. Note: *Page numbers optional depending on journal requirements. Hopewell S, Clarke M, Moher D, Wager E, Middleton P, Altman DG, et al. CONSORT for reporting randomised trials in journal and conference abstracts. Lancet. 2008;371:281–283.