The original description of central sensitization

Mapping Intimacies ◽

10.1093/med/9780198834359.003.0040 ◽

2018 ◽

Author(s):

Sheila Black

Keyword(s):

Amino Acids ◽

Dorsal Horn ◽

Central Sensitization ◽

Excitatory Amino Acids ◽

Formalin Test ◽

Tissue Injury ◽

Original Description ◽

Nociceptive Responses ◽

Landmark Study

The landmark study discussed in this chapter is ‘The contribution of excitatory amino acids to central sensitization and persistent nociception after formalin-induced tissue injury’, published by Coderre and Melzack in 1992. Previous studies in this field implicate a contribution of excitatory amino acids (EAAs), specifically l-glutamate and l-aspartate, to injury-induced sensitization of nociceptive responses in the dorsal horn of the spinal cord. Repetitive stimulation of primary afferent fibres demonstrated that l-glutamate and NMDA can produce ‘wind-up’ of neuronal dorsal horn activity, and this is blocked by application of NMDA antagonists. This study uses the formalin test as a behavioural model to investigate the mechanisms underlying central sensitization and the role of EAAs, NMDA, their receptors, and their antagonists in this process.

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The contribution of excitatory amino acids to central sensitization and persistent nociception after formalin-induced tissue injury

Journal of Neuroscience ◽

10.1523/jneurosci.12-09-03665.1992 ◽

1992 ◽

Vol 12 (9) ◽

pp. 3665-3670 ◽

Cited By ~ 399

Author(s):

TJ Coderre ◽

R Melzack

Keyword(s):

Amino Acids ◽

Central Sensitization ◽

Excitatory Amino Acids ◽

Tissue Injury

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Acetaminophen Inhibits Spinal Prostaglandin E2Release after Peripheral Noxious Stimulation

Anesthesiology ◽

10.1097/00000542-199907000-00032 ◽

1999 ◽

Vol 91 (1) ◽

pp. 231-239 ◽

Cited By ~ 102

Author(s):

Uta S. Muth-Selbach ◽

Irmgard Tegeder ◽

Kay Brune ◽

Gerd Geisslinger

Keyword(s):

Spinal Cord ◽

Urinary Excretion ◽

Dorsal Horn ◽

Formalin Test ◽

Intraperitoneal Administration ◽

Noxious Stimulation ◽

Cyclooxygenase Inhibitor ◽

Nociceptive Processing ◽

Pge2 Release

Background Prostaglandin play a pivotal role in spinal nociceptive processing. At therapeutic concentrations, acetaminophen is not a cyclooxygenase inhibitor. inhibitor. Thus, it is antinociceptive without having antiinflammatory or gastrointestinal toxic effects. This study evaluated the role of spinal prostaglandin E2 (PGE2) in antinociception produced by intraperitoneally administered acetaminophen. Methods The PGE2 concentrations in the dorsal horn of the spinal cord were measured after formalin was injected into the hind paw of rats. The effect of antinociceptive doses of acetaminophen (100, 200, and 300 mg/kg given intraperitoneally) on PGE2 levels and flinching behavior was monitored Spinal PGE2 and acetaminophen concentrations were obtained by microdialysis using a probe that was implanted transversely through the dorsal horn of the spinal cord at L4. Furthermore, the effects of acetaminophen on urinary prostaglandin excretion were determined. Results Intraperitoneal administration of acetaminophen resulted in a significant decrease in spinal PGE2 release that was associated with a significant reduction in the flinching behavior in the formalin test Acetaminophen was distributed rapidly into the spinal cord with maximum dialysate concentrations 4560 min after intraperitoneal administration. Urinary excretion of prostanoids (PGE2, PGF2alpha, and 6-keto-PGF1alpha) was not significantly altered after acetaminophen administration. Conclusions The data confirm the importance of PGE2 in spinal nociceptive processing. The results suggest that antinociception after acetaminophen administration is mediated, at least in part, by inhibition of spinal PGE2 release. The mechanism, however, remains unknown. The finding that urinary excretion of prostaglandins was not affected might explain why acetaminophen is antinociceptive but does not compromise renal safety.

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