The induction and maintenance of central sensitization is dependent on N -methyl-d-aspartic acid receptor activation; implications for the treatment of post-injury pain hypersensitivity states

Abstract

The consequence of the temporal summation of slow synaptic potentials and that the slow potentials and windup are reduced by pretreatment with N-methyl-d-aspartic acid (NMDA) antagonists. We have now examined whether primary afferent induced hypersensitivity states in flexor motoneurones are also dependent on the activation of NMDA receptors and whether windup is a possible trigger for the production of the central hypersensitivity. Both a non-competitive (MK-801) and a competitive (D-CPP) NMDA antagonist, at doses that did not modify the baseline reflex, reduced the facilitation of the flexor reflex produced by either brief electrical stimulation of the sural nerve (1 Hz for 20 sec at C-fibre strength), or by the cutaneous application of the chemical irritant mustard oil. These antagonists also prevented windup from occurring in the motoneurones. When the the MK-801 and the D-CPP were administered once a state of central facilitation had been induced by prior treatment with mustard oil, they returned the facilitated reflex to its pretreatment level. These results indicate that NMDA receptors are involved in the induction and maintenance of the central sensitization produced by high threshold primary afferent inputs. Because central sensitization is likely to contribute to the post-injury pain hypersenstivity states in man, these data have a bearing both on the potential role of NMDA antagonists for pre-emptive analgesia and for treating established pain states. ∗Correspondence to: Dr. C.J. Woolf, Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, U.K. Submitted July 2, 1990; revised August 28, 1990; accepted August 31, 1990. © Lippincott-Raven Publishers....