Primary Analgesic Action of Acetaminophen and Rofecoxib in Osteoarthritis

BACKGROUND:

Pain appears to be the most important symptom of osteoarthritis (OA), which causes individuals to seek medical treatment. However, the structural damages in OA patients do not correlate well with the intensity of pain. In OA pain treatment, rofecoxib was recently shown to have some advantages over acetaminophen (Geba et al. 2002).

OBJECTIVES:

In order to better understand the molecular basis of OA pain and its association with acetaminophen or rofecoxib therapy, we evaluated the changes of the peripheral inflammatory mediator, serotonin; the neuropeptide, substance P; the endogenous opioid, beta-endorphin; as well as opioid receptor kappa (KOR) after the application of either acetaminophen or rofecoxib. This study was designed to provide novel insights of analgesic action of these two drugs in symptomatic OA.

METHODS:

20 patients with symptomatic knee OA were randomly allocated into two groups treated with either acetaminophen up to 4g/d (n=10) or rofecoxib 25mg/d (n=10) for 3 months. Visits and measurements were scheduled upon entry (T0), month 1 (T1) and month 3 (T3). The serum serotonin, plasma beta-endorphin and substance P levels were determined via commercial ELISA kits. Expression of KOR mRNA in PBMC was evaluated by Taqman real time PCR.

RESULTS:

As shown in the table, both acetaminophen and rofecoxib alleviated pain significantly in three months, when assessed by VAS (-4.07, P=0.0176 and -4.25, P=0.0049, respectively); and rofecoxib tended to be more efficient than acetaminophen after one month medication (rofecoxib: -4.15, P=0.0049; acetaminophen: -2.10, P=0.0204). Plasma beta-endorphin levels decreased dramatically in the acetaminophen group. Serotonin dropped in the rofecoxib group from T0 to T1. No significant changes were detected in the acetaminophen group. In both groups levels of plasma substance P were found to be elevated at T1. Although in OA patients, KOR mRNA expression was reduced considerably (data not shown), no modulation was observed in both groups after medication.

CONCLUSION:

Although acetaminophen and rofecoxib are both efficient pain medications in symptomatic OA, they are likely to act differently on their analgesic pathways. Acetaminophen may be involved in the delivery of peripheral beta-endorphin to local injured tissue and thereby relieve joint pain and/or centrally in the brain by suppressing COX-3; while rofecoxib may primarily act on the serotonin pathway and control the release of inflammatory mediators. Both drugs have no effects on peripheral KOR. It is interesting that rofecoxib appears rather rapid analgesic, in comparison with acetaminophen.