Chronic pain, whether the result of nerve trauma or persistent inflammation, is a debilitating condition that exerts a high social cost in terms of productivity, economic impact and quality of life. Currently available therapies yield limited success in treating such pain, suggesting the need for new insight into underlying mechanism(s). Here, we examine the likelihood that sustained activation of descending modulatory pathways that facilitate pain transmission could underlie some states of chronic pain. Such activation of descending facilitatory pathways might be the result of neuroplastic changes that occur at medullary sites in response to persistent input of pain signals. Understanding the mechanisms of descending facilitation and the spinal effects of such discharge could provide new insights into the modulation of chronic pain.