Spinal cord dynorphin: positive region-specific modulation during pregnancy and parturition

In laboratory animals and humans, pregnancy is associated with opioid-mediated elevations in the threshold for responsiveness to aversive stimuli. Previous pharmacological analysis has demonstrated that this analgesia results, at least in part, from the activation of spinal cord kappa opioid receptors utilizing dynorphin as the major opioid substrate. The present report demonstrates that during late pregnancy, the content of spinal dynorphin A(1-17 and 1-8) is altered in a region-specific fashion. As a result, levels of dynorphin peptides are elevated, but only in the lumbar spinal region. In parturient animals, lumbar levels of dynorphin A(1-8) remained elevated but there was an additional increment in the content of dynorphin A(1-17). During late gestation, spinal content of Met-enkephalin and its precursor are also elevated, but, in contrast to dynorphin peptides, there is no interaction between condition and spinal level. Possible analgesic synergy between mu-delta and kappa opioid receptor systems is discussed. It is concluded that some parameter(s) of the pregnant condition triggers the activation of a spinal cord dynorphin system that attenuates the pain associated with late pregnancy and labor.