Clinical experience with duloxetine in the management of chronic musculoskeletal pain. A focus on osteoarthritis of the knee

Abstract

Duloxetine is a serotonin and norepinephrine reuptake inhibitor (SNRI) with central nervous system activity. Its analgesic efficacy in central pain is putatively related to its influence on descending inhibitory pain pathways. The analgesic efficacy of duloxetine has been demonstrated in four distinct chronic pain conditions. These include neuropathic pain associated with diabetic peripheral neuropathy, fibromyalgia, chronic low back pain, and osteoarthritis knee pain (OAKP). The purpose of this review is to examine the clinical efficacy and safety of duloxetine in the management of chronic OAKP. Three separate randomized, double-blind placebo-controlled trials have demonstrated that (1) a clinically meaningful decrease in pain severity occurs at about 4 weeks relative to placebo, (2) patients receiving duloxetine report better improvements in physical functioning relative to placebo, (3) duloxetine is safe and effective when used adjunctively with nonsteroidal anti-inflammatory drugs, and (4) that there are no new safety signals beyond what has been observed in other indications.

Keywords: Chronic pain management; drug interactions; duloxetine; osteoarthritis.

Figure 1.

Ascending nociceptive pathways transmit/conduct noxious stimuli from the peripheral regions of the body to the brain. Descending modulatory pain pathways alter the processing of pain signals. Chronic pain, like that associated with knee osteoarthritis (OA), results in changes in the central nervous system, which likely reflect alterations in supraspinal modulation of nociception, and include increases in excitatory and decreases in inhibitory modulation pathways. In the descending modulatory pain system, the neurotransmitters 5-hydroxytryptamine (5-HT) and norepinephrine (NE) modulate pain signals. 5-HT both inhibits and facilitates the perception of pain. 5-HT inhibits pain via the descending inhibitory arm of the descending modulatory pathway and facilitates the perception of pain via the descending facilitatory arm of the descending modulatory pathway. NE inhibits the perception of pain via the descending inhibitory arm of the descending modulatory pathway. NE does not seem to be involved in the facilitatory aspect of pain perception in the descending modulatory pathway.