Opioid and Non-Opoid Actions of Dynorphin A on Spinal Wide Dynamic Range Neurons

Abstract

Dynorphin A is an endogenous peptide that can activate opioid receptors and bradykinin receptors; the latter has been proposed to be a mechanism of dynorphin A’s pronociceptive actions. Sensitization of wide dynamic range (WDR) neurons in the spinal dorsal horn causes innocuous stimuli to be perceived as pain. Under conditions of chronic inflammation, elevated levels of dynorphin A are found in he spinal cord and could contribute to central sensitization by modulating WDR neuron function. To test the effect of dynorphin A on WDR neurons, we performed in vivo extracellular recordings on the spinal cord of anesthetized rats in the presence of a dose range of an opioid, dynorphin A (1-13), or non-opioid dynorphin A (2-13). WDR neurons’ response was attenuated in naïve rats by dynorphin A (1-13). Dynorphin A (2-13) did not potentiate WDR response to nociceptive inputs in naive rats. These findings suggest that the pronociceptive actions of intrathecal dynorphin A is unlikely to be mediated by activation of the WDR neurons in physiological conditions. A fragment of dynorphin A, LYS1044, retains high affinity for bradykinin receptors but has no agonist activity, and could provide a basis for therapeutics using dynorphin A as a new modality for pain.