» Articles » PMID: 1828878

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

Overview
Journal Pain
Specialties Neurology
Psychiatry
Date 1991 Mar 1
PMID 1828878
Citations 369
Authors
Affiliations
Soon will be listed here.
Abstract

Repetitive stimulation of small diameter primary afferent fibres produces a progressive increase in action potential discharge (windup) and a prolonged increase in the excitability of neurones in the spinal cord following the stimulus. Previous studies have demonstrated that windup is 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 hypersensitivity 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.

Citing Articles

Intrathecal magnesium sulphate as an adjuvant to bupivacaine for infraumbilical surgeries: An updated systematic review and meta-analysis.

Belal M, Alazki O, Bashir M, Sbitan L, Albelal D, Albakkar F Indian J Anaesth. 2025; 69(1):86-107.

PMID: 40046712 PMC: 11878353. DOI: 10.4103/ija.ija_862_24.


The efficacy of acupuncture in relieving postoperative pain in patients with low simple anal fistula: Protocol of a prospective, randomised, controlled trial.

Yang M, Zheng D, Jin X, Tang H, Cao W, Ye Q PLoS One. 2025; 20(1):e0317902.

PMID: 39854599 PMC: 11761113. DOI: 10.1371/journal.pone.0317902.


Visceral Pain in Preterm Infants with Necrotizing Enterocolitis: Underlying Mechanisms and Implications for Treatment.

Ten Barge J, van den Bosch G, Slater R, van den Hoogen N, Reiss I, Simons S Paediatr Drugs. 2025; 27(2):201-220.

PMID: 39752054 PMC: 11829917. DOI: 10.1007/s40272-024-00676-0.


Impact of electro-acupuncture on EAAT2 and NMDAR-2B expression in goats with visceral hypersensitivity.

Tahir A, Ding Y, Wan J, Shah M, Janyaro H, Li X Heliyon. 2024; 10(23):e40700.

PMID: 39717594 PMC: 11665384. DOI: 10.1016/j.heliyon.2024.e40700.


Pathophysiology of Pain and Mechanisms of Neuromodulation: A Narrative Review (A Neuron Project).

Karcz M, Abd-Elsayed A, Chakravarthy K, Aman M, Strand N, Malinowski M J Pain Res. 2024; 17:3757-3790.

PMID: 39583192 PMC: 11581984. DOI: 10.2147/JPR.S475351.