NYX-2925, A NOVEL, NON-OPIOID, SMALL-MOLECULE MODULATOR OF THE N-METHYL-d-ASPARTATE RECEPTOR (NMDAR), DEMONSTRATES POTENTIAL TO TREAT CHRONIC, SUPRASPINAL CENTRALIZED PAIN CONDITIONS

Pain is both a sensory and emotional experience, which serves an adaptive purpose by protecting the body from prolonged and repeated tissue damage. However, the presence of chronic pain can transition to a maladaptive state leading to life-long suffering and is currently a health care burden due to limited effective pharmacotherapies. This review aims to describe the transition to a chronic pain state and the central changes (supraspinal) that occur to prolong the unpleasant feelings of pain. In addition to alterations in the periphery and spinal cord, regions in the brain involved in pain perception as well as executive functioning undergo changes in activity that reflect painful experiences from nonpainful stimuli. These pathological changes to the nociceptive system are partly mediated by expression and activity patterns of N-methyl-d-aspartate receptors (NMDARs), which process and propagate excitatory transmission in response to glutamate release in the periphery, spinal cord, and brain and have an important role in learning and memory. Importantly, NMDARs have been implicated in the cellular mechanisms responsible for the maintenance of the centralized, chronic pain state within the brain. Here we present preclinical data describing the analgesic effects of NYX-2925, a novel NDMAR modulator in a variety of neuropathic pain rodent models. These data provide compelling evidence that targeting brain regions responsible for the affective and cognitive aspects of pain may alleviate chronic pain and serve as a novel mechanism to treat chronic pain conditions, including those refractory to current analgesics.