Prostanoid receptor EP1 and Cox-2 in injured human nerves and a rat model of nerve injury: a time-course study

Autor: Alex W. Wilson, Royston A. Gray, Pascal F. Durrenberger, Iain P. Chessell, Praveen Anand, Rolfe Birch, Sharon Bingham, Nicola C. Day, Paul Facer, Maria A Casula, Sue D. Collins, Yiangos Yiangou, David Elliot
Jazyk: angličtina
Rok vydání: 2006
Předmět:
Male
Pathology
INFLAMMATORY PAIN
PATHOLOGICAL PAIN
Neoplasms
Nerve Tissue
lcsh:RC346-429
Rats
Sprague-Dawley
Neuroma
Sciatica
Ganglia
Spinal
NEUROPATHIC PAIN
General Medicine
Middle Aged
CYCLOOXYGENASE-2 EXPRESSION
Receptors
Prostaglandin E
EP1 Subtype
Sciatic Nerve
PERIPHERAL INFLAMMATION
medicine.anatomical_structure
Peripheral nerve injury
Neuropathic pain
SPINAL PROSTAGLANDIN E-2
Female
Sciatic nerve
Microglia
medicine.symptom
MESSENGER-RNA
Life Sciences & Biomedicine
Research Article
Adult
medicine.medical_specialty
Central nervous system
Clinical Neurology
PERITONEAL-MACROPHAGES
SCIATIC-NERVE
FORMALIN TEST
medicine
Animals
Humans
Receptors
Prostaglandin E
Brachial Plexus
Neurons
Afferent
lcsh:Neurology. Diseases of the nervous system
Aged
Science & Technology
Neurology & Neurosurgery
business.industry
Macrophages
1702 Cognitive Science
Nerve injury
medicine.disease
Spinal cord
Rats
Disease Models
Animal
Cyclooxygenase 2
Neurosciences & Neurology
Neurology (clinical)
1109 Neurosciences
business
Brachial plexus
Zdroj: BMC Neurology, Vol 6, Iss 1, p 1 (2006)
BMC Neurology
ISSN: 1471-2377
Popis: Background Recent studies show that inflammatory processes may contribute to neuropathic pain. Cyclooxygenase-2 (Cox-2) is an inducible enzyme responsible for production of prostanoids, which may sensitise sensory neurones via the EP1 receptor. We have recently reported that while macrophages infiltrate injured nerves within days of injury, they express increased Cox-2-immunoreactivity (Cox-2-IR) from 2 to 3 weeks after injury. We have now investigated the time course of EP1 and Cox-2 changes in injured human nerves and dorsal root ganglia (DRG), and the chronic constriction nerve injury (CCI) model in the rat. Methods Tissue sections were immunostained with specific antibodies to EP1, Cox-2, CD68 (human macrophage marker) or OX42 (rat microglial marker), and neurofilaments (NF), prior to image analysis, from the following: human brachial plexus nerves (21 to 196 days post-injury), painful neuromas (9 days to 12 years post-injury), avulsion injured DRG, control nerves and DRG, and rat CCI model tissues. EP1 and NF-immunoreactive nerve fibres were quantified by image analysis. Results EP1:NF ratio was significantly increased in human brachial plexus nerve fibres, both proximal and distal to injury, in comparison with uninjured nerves. Sensory neurones in injured human DRG showed a significant acute increase of EP1-IR intensity. While there was a rapid increase in EP1-fibres and CD-68 positive macrophages, Cox-2 increase was apparent later, but was persistent in human painful neuromas for years. A similar time-course of changes was found in the rat CCI model with the above markers, both in the injured nerves and ipsilateral dorsal spinal cord. Conclusion Different stages of infiltration and activation of macrophages may be observed in the peripheral and central nervous system following peripheral nerve injury. EP1 receptor level increase in sensory neurones, and macrophage infiltration, appears to precede increased Cox-2 expression by macrophages. However, other methods for detecting Cox-2 levels and activity are required. EP1 antagonists may show therapeutic effects in acute and chronic neuropathic pain, in addition to inflammatory pain.
Databáze: OpenAIRE
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