The role of the central nervous system in the generation and maintenance of chronic pain in rheumatoid arthritis, osteoarthritis and fibromyalgia

Abstract

Pain is a key component of most rheumatologic diseases. In fibromyalgia, the importance of central nervous system pain mechanisms (for example, loss of descending analgesic activity and central sensitization) is well documented. A few studies have also noted alterations in central pain processing in osteoarthritis, and some data, including the observation of widespread pain sensitivity, suggest that central pain-processing defects may alter the pain response in rheumatoid arthritis patients. When central pain is identified, different classes of analgesics (for example, serotonin-norepinephrine reuptake inhibitors, α2δ ligands) may be more effective than drugs that treat peripheral or nociceptive pain (for example, nonsteroidal anti-inflammatory drugs and opioids).

Figure 1

Descending pain pathways and central sensitization. Descending pain pathways and central sensitization modulate the pain response in the dorsal horn of the spinal cord. Descending analgesic pathways include the serotonin-norepinephrine and opioidergic descending pathways, which dampen pain sensitivity response. Loss of descending analgesia leads to hyperalgesia and allodynia. Central sensitization occurs through the action of glutamate on the N-methyl-D-aspartate (NMDA) receptor, resulting in an increase in intracellular calcium levels and kinase activation, leading to hyperalgesia and allodynia.