A stable prostacyclin analog enhances ectopic activity in rat sensory neurons following neuropathic injury

• Published in: Brain research Vol. 904; no. 1; pp. 85 - 92
• Main Authors: Omana-Zapata, Imelda, Bley, Keith R
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 15.06.2001; Amsterdam Elsevier; New York, NY
• Subjects: Action Potentials - drug effects; Action Potentials - physiology; Animals; Biological and medical sciences; COX inhibitors; Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - pharmacology; Drug Interactions - physiology; Ganglia, Spinal - drug effects; Ganglia, Spinal - physiopathology; Heart Rate - drug effects; Heart Rate - physiology; Inflammation - chemically induced; Inflammation - pathology; Inflammation - physiopathology; Isoenzymes - antagonists & inhibitors; Isoenzymes - metabolism; Male; Medical sciences; Nervous system (semeiology, syndromes); Neuralgia - chemically induced; Neuralgia - pathology; Neuralgia - physiopathology; Neurology; Neurons, Afferent - drug effects; Neurons, Afferent - physiology; Neuropathic pain; Peripheral Nerves - pathology; Peripheral Nerves - physiopathology; Peripheral Nerves - surgery; Peripheral Nervous System Diseases - chemically induced; Peripheral Nervous System Diseases - pathology; Peripheral Nervous System Diseases - physiopathology; Prostaglandin-Endoperoxide Synthases - metabolism; Prostaglandins - pharmacology; Prostanoid; prostanoids; Rats; Rats, Sprague-Dawley; Receptors, Prostaglandin - agonists; Receptors, Prostaglandin - antagonists & inhibitors; Receptors, Prostaglandin - metabolism; Sensitization; Sensory neurons; Sensory systems; Sensory neurons; Sensitization; Prostanoid; COX inhibitors; Neuropathic pain; Prostaglandin-endoperoxide synthase; Nervous system diseases; Prostaglandin I2; Rat; Enzyme; Rodentia; Enzyme inhibitor; Peripheral neuropathy; Vertebrata; Experimental disease; Mammalia; Pain; Analog; Animal; Sensory neuron; Oxidoreductases; Sciatic nerve
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(01)02486-6

Prostanoids sensitize sensory afferents during inflammation. However, their role in neuropathic pain is still unclear. We analyzed the actions of prostanoids, non-selective (indomethacin) or selective (celecoxib and NS-398) cyclooxygenase-2 (COX or COX-2) inhibitors, on the ectopic activity of dorsal root ganglia (DRG) and dorsal horn (DH) neurons in a model of neuropathic injury. Extracellular recordings of DRG and DH neurons and cardiovascular measurements were performed on anesthetized, paralyzed and artificially ventilated adult male Sprague-Dawley rats whose sciatic nerve had been transected. PGD 2, PGE 2, PGF 2α, carbaprostacyclin (cPGI 2; a stable prostacyclin analog), and carbocyclic thromboxane (cTXA 2) were administered at cumulative doses (0.0001–5 mg/kg, i.p.) at 5 or 10 min intervals. Only cPGI 2 significantly increased the DRG and DH activity in a dose-dependent manner, with ED 50 values of 0.05 (0.01–0.96) and 0.69 (0.11–1.04) mg/kg, respectively. The other prostanoids did not significantly increase activity, although they reduced heart rate for up to 5 min following administration. Time course experiments with single doses of cPGI 2 (1 mg/kg, i.v.) increased DH discharge rate 3–17 min after injection. Indomethacin (3 mg/kg, s.c.), but not celecoxib or NS-398 (both at 6 mg/kg, s.c.), reduced both DRG and DH activity. Our results indicate that cPGI 2 excites DRG and DH neurons of neuropathic rats, and may suggest a role for IP prostanoid receptors in pain episodes associated with nerve injury. The inhibitory effect of indomethacin, but not celecoxib or NS-398, on ectopic activity may suggest that a tonic generation of PGI 2 by COX-1 could contribute to neuropathic pain.