The anti-inflammatory and analgesic activity of curcumin in a rat model of full thickness thermal injury

Each year there are approximately 45,000 burn injuries requiring hospitalization in the US, and opioids are the primary analgesic for these patients. However a range of side effects, as well as a high potential for addiction, often limit dose levels and frequency of use. There is therefore a need to develop effective non-opioid alternatives for treating burn pain. The purpose of this investigation was to assess the potential of curcumin, a naturally occurring anti-inflammatory agent that is highly abundant in the spice turmeric (Curcuma longa), as an analgesic for thermal injury pain. To accomplish this, male rats were subjected to a hind paw full thickness thermal injury protocol. The latency to paw withdrawal (PWL) from a noxious thermal stimulus or a mechanical stimulus was recorded prior to thermal injury (baseline), and at 24, 48, and 72 hours, and 1 week following thermal injury. We demonstrate that curcumin treatment attenuated thermal hyperalgesia and mechanical allodynia, as measured by an extended PWL. This effect was most pronounced after 1 week of treatment. Using multiplex cytokine antibody arrays, we also assessed the ability of curcumin to block heat-induced secretion of cytokines and other inflammatory mediators in cultured keratinocytes, the cell type most prevalent at the burn site. We demonstrate that curcumin suppressed heat induced secretion of GRO-α and IL-8 and both basal levels and heat-induced matrix metalloproteinase 1 and 3 (MMP-1 and MMP-3). Finally, we show that curcumin treatment suppressed heat induced p38 MAPK activity and both basal levels and heat-induced NF-κB p65 activity, as measured by levels of phosphorylated p38 and NF-κB p65, respectively. Our data indicate that curcumin may be an effective analgesic for thermal injury pain and that this effect could be mediated through suppression of inflammation at the site of injury.