by Aaron Gochman (’18)

The biological mechanisms for acute and chronic pain appear to be vastly different, with the understanding for that of chronic pain proving much more elusive. However, an international team of researchers may have discovered a link between the two in a recent study.

NMDA receptors (NMDAR) have a diverse role in neurological function. They modulate neurotransmission, the process of transducing signals across neuronal networks. NMDAR have been implicated in a wide spectrum of neurological diseases, spanning from acute (stroke, epilepsy) to chronic (schizophrenia, Parkinson’s disease). In this study, the team focused on NMDAR in the spinal cord in the context of the transition from acute to chronic pain.

The researchers found that β-arrestin-2, a member of the β-arrestin protein family, modulated NMDAR function during mechanical allodynia, an important step in pain pathogenesis. β-arrestin-2 was shown to be an important regulator of pain as mice lacking Arrb2, the gene that codes for β-arrestin-2, were not able to contain the spread of inflammation. In fact, over-expression of β-arrestin-2 appeared to reverse the molecular symptoms of the pain signaling pathway.

β-arrestin-2 may represent a key regulator in the transition from acute to chronic pain and a novel pharmacological inhibitor of NMDAR during pain pathogenesis.

References:

1. G. Chen, et al., [beta]-arrestin-2 regulates NMDA receptor function in spinal lamina II neurons and duration of persistent pain. Nat Commun 7, (2016).