Cyclooxygenase 2 expression in the spared nerve injury model of neuropathic pain
Section snippets
Animals
Male Sprague–Dawley rats (150–200 g) were obtained from Charles River Laboratories (Wilmington, MA, USA) and were housed under a 12-h light/dark cycle with lights on at 07:00 h and food and water ad libitum. All procedures were performed in accordance with the Massachusetts General Hospital Subcommittee on Research Animal Care and the National Institutes of Health guide for the care and use of laboratory animals. Every effort was undertaken to minimize the number of animals used and their
RNase protection assays
Following SNI surgery, a very small, but reproducible transient increase in COX-2 mRNA was seen in the dorsal spinal cord by RNase protection assay (Fig. 1a). Only very small changes in mRNA expression (approximately 15%) were seen at 12 and 24 h and expression appeared to return to sham levels at 72 h after SNI. On day 7 following surgery, expression of COX-2 mRNA fell slightly below that seen in sham animals. In contrast, and as reported previously (Samad et al., 2001), a large but transient
Discussion
COX-2 expression in the dorsal horn of the spinal cord does not markedly change following SNI in the rat, although small variations in mRNA and protein levels are seen that may reflect the effect of inflammation associated with surgery. The COX-2 inhibitor rofecoxib did not affect either spontaneous EPSC activity or the amplitude of the AMPA or NMDA responses in the spinal cord following SNI. This indicates that COX-2 is not involved in dorsal horn neurotransmission following SNI and is
Acknowledgements
Supported by the NIH, NS39518 and NS38253, Merck and Co., Inc (C.J.W.) and by BMBF 01EM0103 (G.G.). Portions of this study were presented in abstract form at The Society for Neuroscience annual meeting, November 2–7, 2002, Orlando, FL.
References (40)
- et al.
Diversity of expression of the sensory neuron-specific TTX-resistant voltage-gated sodium ion channels SNS and SNS2
Mol Cell Neurosci
(2000) - et al.
A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man
Pain
(1988) - et al.
Spared nerve injuryAn animal model of persistent peripheral neuropathic pain
Pain
(2000) - et al.
A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia
Pain
(1988) - et al.
The potential role of spinal cord cyclooxygenase-2 in the development of Freund's complete adjuvant-induced changes in hyperalgesia and allodynia
Neuroscience
(1997) - et al.
Role for both spinal cord COX-1 and COX-2 in maintenance of mechanical hypersensitivity following peripheral nerve injury
Brain Res
(2002) - et al.
A stable prostacyclin analog enhances ectopic activity in rat sensory neurons following neuropathic injury
Brain Res
(2001) - et al.
Prostanoids and painUnraveling mechanisms and revealing therapeutic targets
Trends Mol Med
(2002) - et al.
A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury
Pain
(1990) - et al.
Efficacy of pharmacological treatments of neuropathic painAn update and effect related to mechanism of drug action
Pain
(1999)
Intrathecal NSAIDS attenuate inflammation-induced neuropeptide release from rat spinal cord slices
Pain
Hyperalgesia due to nerve injuryRole of prostaglandins
Neuroscience
Effects of cyclooxygenase products of arachidonic acid metabolism on cutaneous nociceptive threshold in the rat
Brain Res
Neuropathic painAetiology, symptoms, mechanisms, and management
Lancet
Characterization of time course of spinal amino acids, citrulline and PGE2 release after carrageenan/kaolin-induced knee joint inflammationA chronic microdialysis study
Pain
Blind patch-clamp recordings from substantia gelatinosa neurons in adult rat spinal cord slicesPharmacological properties of synaptic currents
Neuroscience
Spinal cyclooxygenase-2 is involved in development of allodynia after nerve injury in rats
Neuroscience
PGE2 selectively blocks inhibitory glycinergic neurotransmission onto rat superficial dorsal horn neurons
Nat Neurosci
Peripheral inflammation facilitates Aβ fiber-mediated synaptic input to the substantia gelatinosa of the adult rat spinal cord
J Neurosci
Direct activation of rat spinal dorsal horn neurons by prostaglandin E2
J Neurosci
Cited by (92)
Inhibition of COX-2 alleviates lumbar spinal stenosis-induced chronic mechanical allodynia in rats
2019, International ImmunopharmacologyUnderstanding and Treating Chiari-like Malformation and Syringomyelia in Dogs
2018, Topics in Companion Animal MedicineRedoxins in peripheral neurons after sciatic nerve injury
2015, Free Radical Biology and MedicineProstacyclin mediates neuropathic pain through interleukin 1β-expressing resident macrophages
2014, PainCitation Excerpt :In this regard it has been shown that the nonselective cyclooxygenase (COX) inhibitor ibuprofen, but not the selective COX-2 inhibitor celecoxib, reduced in rats the nociceptive behavior in a neuropathic pain model if administered shortly after injury [41]. Similarly the COX-2 selective inhibitor rofecoxib was unable to alter nociceptive behavior in the spared nerve injury model (SNI) for neuropathic pain in rats [8], suggesting in rats a role for COX-1–derived prostanoids in neuropathic pain development. To date, a function of prostaglandin I2 (prostacyclin, PGI2) in the development of neuropathic pain has not been described, although the pronociceptive role of prostacyclin in the peripheral nervous system is well established.
Prevention of chronic postoperative pain: Cellular, molecular, and clinical insights for mechanism-based treatment approaches
2013, Progress in NeurobiologyCitation Excerpt :However, the preferential regulation of spinal COX-1 and/or COX-2 likely depends on the specific models used. For example, intraplantar paw FOR strongly up-regulates COX-1, but not so much COX-2 (Zhang et al., 2007b), while intraplantar paw CFA and CAR induce robust increases in spinal COX-2 expression (Broom et al., 2004; Ibuki et al., 2003; Seybold et al., 2003). In line with this, intrathecal injection with the specific COX-2 inhibitor NS-398 given within 2 h following intraplantar paw CAR strongly reduced pain hypersensitivity (Ibuki et al., 2003).
Endocannabinoid biosynthetic enzymes regulate pain response via LKB1-AMPK signaling
2023, Proceedings of the National Academy of Sciences of the United States of America