Lipoxins Reduce Chronic Pain
The chronic pain associated with inflammatory diseases is a prevalent, persistent and debilitating problem. When a person has an inflammatory condition, the specialized nerve cells that compose the pain pathway become sensitized, leading to overactive pain responses to both harmful and non-harmful stimuli. For example, a bed sheet that touches a gout-inflamed toe may feel excruciating, although the sheet will not actually cause any additional injury to that toe. In a healthy person, inflammation and pain sensitivity are temporary – when the injury heals, the body returns to a state of pain-free health. Unfortunately, this reversal does not happen as designed in people with chronic inflammatory diseases, such as rheumatoid arthritis and systemic lupus erythematosus.
What Problem Was Studied?
Many of the chemical factors involved in initiating inflammation in the body also drive pain sensitization found with inflammation. Likewise, studies have shown that various chemical mediators are involved in “turning off” inflammation and pain. So, scientists are seeking answers as to how they can extinguish the inflammatory response and desensitize the pain pathways.
Lipoxins are one such class of mediators that have been found to act as “braking signals” in inflammation. Arthritis Foundation-funded researcher Camilla I. Svensson, PhD, of the University of California, San Diego, and her colleagues have been studying lipoxins and their role in quieting inflammation and pain signals.
What Was Done in the Study?
Previous studies showed that lipoxins reduce inflammation when administered directly to the inflamed area or when given systemically (via intravenous injection or orally). In fact, aspirin triggers the release of lipoxins as one of its mechanisms for reducing inflammation.
To investigate whether lipoxins block the pain associated with inflammation, the scientists gave lipoxins to laboratory rats, induced inflammation by injecting carrageenan into one hind paw and measured their pain reaction. To quantify their pain, scientists recorded the amount of time it took the rats to withdrawal the paw when a heat lamp was applied. To determine whether the lipoxins acted at the site of inflammation or in the spinal cord, the research team injected lipoxins intravenously into some rats and directly into the spinal cords in others, still others had fluid injected that contained no lipoxins.
What Were the Study Results?
When lipoxins were administered intravenously (and hence went throughout the body), paw withdrawal times were lengthened compared with control rats – indicating that lipoxins can alter pain processing. The carrageenan-injected paw also showed a reduction in swelling – indicating that intravenously administered lipoxins can provide local anti-inflammatory action.
When lipoxins were administered into the spinal column, paw withdrawal times were also lengthened. However, the spinally administered lipoxins had no effect on paw swelling. These results indicate that lipoxins reduce pain sensitivity when
delivered systemically or spinally. It is believed that, depending on where the lipoxins are injected, they reduce pain through different mechanisms.
What Does This Mean for People with Arthritis?
The dual role of lipoxins – having both anti-inflammatory and anti-pain functions – provide insights into a regulatory pathway that effects both peripheral (at the site of inflammation) and central (at the spine) activity. Furthermore, Dr. Svensson concludes, “these results point to novel therapeutic targets for relieving chronic pain.”
Svensson CI, Zattoni M, Serhan CN. Lipoxins and aspirin-triggered lipoxin inhibit inflammatory pain processing. J Exp Med 2007;204:245-52. DOI: 10.1084/jem.20061826