Painful Truth

Pain signals travel to the brain through specialized nerves called nociceptors. These specialized nerves can be found body-wide, including joints, muscles and tendons.

Pain can be a helpful reminder to rest an injured joint. Say you are rushing around the house and bang your knee on the coffee table. Nociceptors detect damage to the tissue and send a message to the brain that says “ouch.”

Once the injury is healed, though, the pain should stop. With joints damaged from the inflammation connected to OA, the pain doesn’t stop, in part because nerve growth factor keeps pain signals on a one-way street to the brain.

Once that pathway is established, chronic pain becomes its own ailment (See “Why You Hurt,” in May/June Arthritis Today).

Richard Brasington MD, a rheumatologist at Washington University School of Medicine in St. Louis, Mo., says that chronic pain from conditions such as OA, rheumatoid arthritis and nerve damage from diabetes, changes the brain in a way that worsens how even mild pain is interpreted. So a hangnail could actually feel like a broken finger.

A Second Chance?

In 2006 and 2007, Dr. Lane and colleagues conducted a study to test whether tanezumab was safe and effective. The team enrolled 450 patients with moderate to severe knee OA and gave them either a placebo or one of five specific doses of tanezumab. Treatments were given on days one and 56. Pain relief was measured out to 16 weeks. Others took a placebo.

In those receiving tanezumab, pain was reduced by 45 to 65 percent. Dr. Lane says that's about double the pain relief that NSAIDs offer. The study was published in 2010 in the New England Journal of Medicine.

Dr. Lane and others are still waiting to hear from the FDA as to whether tanezumab clinical trials can resume, although she expects trials will indeed restart.

The Phase III clinical trial that was halted included people with advanced OA, some of whom had joints with osteonecrosis, a condition that occurs when the blood supply to the hips is disrupted causing tissue death.

Dr. Lane says that doctors see osteonecrosis less often as more people have hip replacement surgery before the condition can occur. She suspects that OA worsened in some people, because, with pain so much better, they were too active and damaged joints already on the edge of failing.

Dr. Lane explains that researchers still need to make certain that tanezumab does not interact with NSAIDs to worsen joints. Patients taking anti-NGF therapy would not need other aspirin-like drugs or opioids, she says.

If anti-NGF trials resume for OA, and the FDA eventually approves tanezumab, it will open the door for other therapies that block nerve growth factor.

“NGF is the tip of the iceberg for what we’ll be able to offer arthritis sufferers,” says Dr. Lane.