Cyclo-oxygenase-2 contributes to central sensitization in rats with peripheral inflammation

• Published in: Pain (Amsterdam) Vol. 105; no. 1; pp. 47 - 55
• Main Authors: Seybold, Virginia S, Jia, Yu-Ping, Abrahams, Lia G
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.09.2003; Elsevier
• Subjects: Action Potentials; Analgesics, Non-Narcotic - administration & dosage; Animals; Biological and medical sciences; Blotting, Western; Cyclo-oxygenase; Cyclooxygenase 2; Dose-Response Relationship, Drug; Electric Stimulation; Flexor reflex; Foot; Freund's Adjuvant; Fundamental and applied biological sciences. Psychology; Hyperalgesia - enzymology; Hyperalgesia - etiology; Hyperalgesia - physiopathology; Ibuprofen; Ibuprofen - administration & dosage; Inflammation - chemically induced; Inflammation - complications; Isoenzymes - metabolism; Male; Muscle, Skeletal - physiopathology; Nerve Fibers; Neurons; Nociception; Nociceptors - physiopathology; Prostaglandin-Endoperoxide Synthases - metabolism; Rats; Rats, Sprague-Dawley; Reflex - drug effects; Sensitization; Sensory Thresholds; Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. Sensory receptors; Spinal cord; Spinal Cord - enzymology; Spinal Cord - physiopathology; Sural Nerve - physiopathology; Vertebrates: nervous system and sense organs; Nociception; Spinal cord; Sensitization; Flexor reflex; Cyclo-oxygenase; Ibuprofen; Prostaglandin-endoperoxide synthase; Rat; Cyclooxygenase 2; Central nervous system; Cyclooxygenase 1; Flexion reflex; Hyperalgesia; Eicosanoid; Prostaglandin; Enzyme; Arachidonic acid derivatives; Rodentia; Excitability; Inflammation; Muscular fiber; Vertebrata; Mammalia; Sensitization; Ibuprofen; Nociception; Spinal cord; Flexor reflex; Sensory neuron; Oxidoreductases; Sural nerve
• ISSN: 0304-3959; 1872-6623
• DOI: 10.1016/S0304-3959(03)00254-9

It has been widely accepted that prostaglandins are involved in peripheral mechanisms of hyperalgesia. Several lines of evidence suggest that prostaglandins also contribute to the mechanisms underlying hyperalgesia at the level of the spinal cord. The nociceptive flexor reflex of the hind limb was used to test the hypothesis that products of cyclo-oxygenase contribute to the increased excitability of spinal neurons during hyperalgesia induced by peripheral injection of complete Freund's adjuvant (CFA) into the hind paw. The reflex was evoked by electrical stimulation of the sural nerve at an intensity that activated A- and C-fibers, and muscle potentials were recorded in hamstring muscles in decerebrate, spinalized rats. Intrathecal administration of (S)-ibuprofen (1–100 nmol) dose-dependently attenuated the flexor reflex in CFA treated rats but had no effect in untreated rats. (R)-Ibuprofen had no effect on the reflex in either control or CFA-treated rats at the dose tested (100 nmol). Western blots of lumbar spinal cord extracts showed increased levels of cyclo-oxygenase (COX)-2 protein in the dorsal spinal cord of rats with peripheral inflammation; no change occurred in the level of COX-1. These results indicate that products of COX-2 contribute to the increased excitability of the spinal cord during persistent peripheral inflammation.