The NMDA-receptor antagonist CPP abolishes neurogenic ‘wind-up pain’ after intrathecal administration in humans

Abstract

Involvement of the NMDA receptor system in the transmission of nociceptive information, including the development of central sensitization and a wind-up phenomenon, has increased interest in NMDA-receptor antagonists as antinociceptive drugs. This case report describes the use of an NMDA receptor antagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) in a carefully selected patient with severe and intractable neurogenic pain in her left leg. The pain syndrome had components of a continuous deep pain, an allodynia, and a wind-up-like component, including afterdischarge and spread of painful sensations outside the territory of the injured nerve. After intrathecal (i.t.) administration of 200 nmol of CPP the continuous deep pain component and allodynia were unchanged, but the following 'wind-up' phenomenon with afterdischarge and spread of the pain sensation in the left half of the body was completely abolished. Another 500 nmol of CPP administered over 2 h did not improve pain relief. Pain thresholds for heat and cold stimulation, measured with a Marstock thermostimulator, did not change. There was no effect on blood pressure, heart rate, sensitivity, reflexes, coordination or motor performance. Psychotomimetic ketamine-like side effects developed 4 h after the last injection of CPP and were probably due to rostral spread of CPP. These early experiences with i.t. administration of NMDA-receptor antagonists to humans indicate that the NMDA-receptor system plays an important role in neurogenic pain and that antagonizing this system may be a useful way to obtain better pain control although psychotomimetic side effects due to rostral spread may be a problem.