The effect of intrathecal mu, delta, kappa, and alpha-2 agonists on thermal hyperalgesia induced by mild burn on hind paw in rats

Abstract

Mild cutaneous thermal injury, leading to a first-degree burn, induces a sensation of burning pain and enhances the pain sensitivity of the skin. Opioid and α(2) receptor agonists are commonly used to reduce such hyperalgesia. We investigated conditions that induced adequate thermal hyperalgesia in rats and compared the effects of μ, δ, κ, and α(2) receptors at the level of the spinal cord in this model. A total of 149 male Sprague-Dawley rats were submitted to this study. A first-degree burn injury was induced in the hind paw by contact with a hot plate. The nociceptive threshold was determined by measuring the time from the application of a light beam to the hind paw to the withdrawal response (paw withdrawal latency, PWL). Various hot-plate exposure times and light beam intensities were tested to determine the conditions that induced adequate hyperalgesia. We also tested the effects of intrathecal morphine (μ agonist), DPDPE ([D-Pen2, D-Pen5] enkephalin, a δ agonist), U50488H (trans(+)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl]-benzacetamide methane sulfonate salt, a κ agonist), and ST-91 (2-[2,6-diethyl-phenylamino]-2-imidazoline, an α(2) agonist) on PWL. A first-degree burn was induced by contact with the hot plate for 45 s. Using current of 5.0 A, PWL was reduced by 40% from baseline. Intrathecally administered morphine, DPDPE, and ST-91, but not U50488H, showed dose-dependent antinociceptive effects in both injured and normal paws. Based on these findings, we could find adequate conditions for thermal hyperalgesia model. In this experimental model, μ, δ, and α(2) receptor agonists produced antinociceptive effects at the level of the spinal cord, but the κ receptor agonist did not.