Cross-linking of ΔF508-CFTR promotes its trafficking to the plasma membrane.

The mechanisms underlying chronic pain states, including osteoarthritis, differ from those underlying acute pain. In chronic pain states, central nervous system (CNS) factors often play a particularly prominent role. In many individuals with chronic pain, pain can occur with minimal or no evidence of ongoing nociceptive input. Medical subspecialties have applied a wide-range of labels to these pain conditions including fibromyalgia, irritable bowel syndrome and interstitial cystitis to name just a few. These same CNS processes can augment or magnify pain when there is ongoing nociceptive input, as in conditions such as osteoarthritis or autoimmune disorders. The hallmark of these 'centrally driven' pain conditions is a diffuse hyperalgesic state identifiable though the use of experimental sensory testing, that has been corroborated by functional neuroimaging. Characteristic symptoms of these central pain conditions include multifocal pain, fatigue, poor sleep, memory complaints and frequent co-morbid mood and anxiety disorders. In contrast to acute and peripheral pain states that are responsive to non-steroidal anti-inflammatory drugs (NSAIDs) and opioids, central pain conditions respond best to CNS neuromodulating agents, such as serotonin-norepinephrine reuptake inhibitors (SNRIs) and anticonvulsants. While osteoarthritis is generally considered a peripherally mediated pain state, a subset of these patients also manifests centrally driven pain characteristics. Thus, osteoarthritis can also be thought of as a "mixed" pain state and this requires a more tailored approach to treatment.