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

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 α₂ 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 α₂ 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 α₂ agonist) on PWL.

Based on these findings, we could find adequate conditions for thermal hyperalgesia model. In this experimental model, μ, δ, and α₂ receptor agonists produced antinociceptive effects at the level of the spinal cord, but the κ receptor agonist did not.