Intrathecal NSAIDS attenuate inflammation-induced neuropeptide release from rat spinal cord slices. 1998

D M Southall, and L R Michael, and R M Vasko
Department of Pharmacology and Toxicology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN 46202-5126, USA Department of Anesthesia, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN 46202-5126, USA.

Inflammation enhances release of neuropeptides from sensory nerve terminals in the spinal cord, and this may contribute to the development of hyperalgesia. In a similar manner, proinflammatory prostaglandins also augment peptide release from sensory neurons. To ascertain whether the inflammation-induced increase in peptide release from spinal cord slices is mediated by production of these eicosanoids, we examined whether intrathecal administration of nonsteroidal antiinflammatory drugs (NSAIDS) could attenuate the effects of inflammation. Unilateral injection of 150 microl of complete Freund's adjuvant (CFA) into the hindpaw of adult Sprague-Dawley rats resulted in a lower threshold for paw withdrawal (hyperalgesia) on 1, 4, and 5 days after injection. Five days after the induction of inflammation, capsaicin-evoked release of immunoreactive substance P (iSP) and immunoreactive calcitonin gene-related peptide (iCGRP) was increased approximately 2-fold in slices of cord tissue from the side ipsilateral to CFA injection, compared to spinal cord slices from the non-inflamed side. Intrathecal administration of 1 microl/h of 10 nmol/microl solution of the NSAID, ketorolac, for 1 day prior to and throughout the inflammation significantly attenuated the inflammation-induced increase in capsaicin-evoked release of both peptides without altering release in cord tissue from the non-inflamed side. Systemic administration of the same amount of ketorolac did not attenuate the effect of inflammation on peptide release. Intrathecal administration of 16 nmol/h (S)-ibuprofen, before and throughout the inflammation, also significantly attenuated the increase in evoked neuropeptide release associated with inflammation, whereas (R)-ibuprofen was ineffective. These results suggest that inhibition of cyclooxygenase at the level of the spinal cord attenuates the augmentation of neuropeptide release induced by peripheral inflammation, and provide further evidence for an action of prostaglandins at central terminals of sensory neurons during inflammation.

UI MeSH Term Description Entries
D007052 Ibuprofen A non-steroidal anti-inflammatory agent with analgesic, antipyretic, and anti-inflammatory properties Advil,Benzeneacetic Acid, alpha-methyl-4-(2-methylpropyl)- trimethylsilyl ester,Brufen,Ibumetin,Ibuprofen, (+-)-Isomer,Ibuprofen, (R)-Isomer,Ibuprofen, (S)-Isomer,Ibuprofen, Aluminum Salt,Ibuprofen, Calcium Salt,Ibuprofen, Copper (2+) Salt,Ibuprofen, Magnesium Salt,Ibuprofen, Potassium Salt,Ibuprofen, Sodium Salt,Ibuprofen, Zinc Salt,Ibuprofen-Zinc,Motrin,Nuprin,Rufen,Salprofen,Trauma-Dolgit Gel,alpha-Methyl-4-(2-methylpropyl)benzeneacetic Acid,Ibuprofen Zinc,Trauma Dolgit Gel
D007278 Injections, Spinal Introduction of therapeutic agents into the spinal region using a needle and syringe. Injections, Intraspinal,Injections, Intrathecal,Intraspinal Injections,Intrathecal Injections,Spinal Injections,Injection, Intraspinal,Injection, Intrathecal,Injection, Spinal,Intraspinal Injection,Intrathecal Injection,Spinal Injection
D008297 Male Males
D009187 Myelitis Inflammation of the spinal cord. Relatively common etiologies include infections; AUTOIMMUNE DISEASES; SPINAL CORD; and ischemia (see also SPINAL CORD VASCULAR DISEASES). Clinical features generally include weakness, sensory loss, localized pain, incontinence, and other signs of autonomic dysfunction. Myelopathy, Inflammatory,Spinal Cord Inflammation,Subacute Necrotizing Myelitis,Infectious Myelitis,Inflammation, Spinal Cord,Inflammations, Spinal Cord,Inflammatory Myelopathies,Inflammatory Myelopathy,Myelitides,Myelitides, Subacute Necrotizing,Myelitis, Infectious,Myelitis, Subacute Necrotizing,Myelopathies, Inflammatory,Necrotizing Myelitides, Subacute,Necrotizing Myelitis, Subacute,Spinal Cord Inflammations,Subacute Necrotizing Myelitides
D009479 Neuropeptides Peptides released by NEURONS as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells. Neuropeptide
D002211 Capsaicin An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS. 8-Methyl-N-Vanillyl-6-Nonenamide,Antiphlogistine Rub A-535 Capsaicin,Axsain,Capsaicine,Capsicum Farmaya,Capsidol,Capsin,Capzasin,Gelcen,Katrum,NGX-4010,Zacin,Zostrix,8 Methyl N Vanillyl 6 Nonenamide,NGX 4010,NGX4010
D005620 Freund's Adjuvant An antigen solution emulsified in mineral oil. The complete form is made up of killed, dried mycobacteria, usually M. tuberculosis, suspended in the oil phase. It is effective in stimulating cell-mediated immunity (IMMUNITY, CELLULAR) and potentiates the production of certain IMMUNOGLOBULINS in some animals. The incomplete form does not contain mycobacteria. Freund Adjuvant,Adjuvant, Freund,Adjuvant, Freund's,Freunds Adjuvant
D006930 Hyperalgesia An increased sensation of pain or discomfort produced by minimally noxious stimuli due to damage to soft tissue containing NOCICEPTORS or injury to a peripheral nerve. Hyperalgesia, Tactile,Hyperalgesia, Thermal,Hyperalgia,Hyperalgia, Mechanical,Hyperalgia, Primary,Hyperalgia, Secondary,Allodynia,Allodynia, Mechanical,Allodynia, Tactile,Allodynia, Thermal,Hyperalgesia, Mechanical,Hyperalgesia, Primary,Hyperalgesia, Secondary,Hyperalgesic Sensations,Mechanical Allodynia,Mechanical Hyperalgesia,Tactile Allodynia,Thermal Allodynia,Allodynias,Hyperalgesias,Hyperalgesias, Thermal,Hyperalgesic Sensation,Mechanical Hyperalgia,Mechanical Hyperalgias,Primary Hyperalgia,Primary Hyperalgias,Secondary Hyperalgia,Secondary Hyperalgias,Sensation, Hyperalgesic,Sensations, Hyperalgesic,Thermal Hyperalgesia
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000894 Anti-Inflammatory Agents, Non-Steroidal Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions. They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects. Analgesics, Anti-Inflammatory,Aspirin-Like Agent,Aspirin-Like Agents,NSAID,Non-Steroidal Anti-Inflammatory Agent,Non-Steroidal Anti-Inflammatory Agents,Nonsteroidal Anti-Inflammatory Agent,Anti Inflammatory Agents, Nonsteroidal,Antiinflammatory Agents, Non Steroidal,Antiinflammatory Agents, Nonsteroidal,NSAIDs,Nonsteroidal Anti-Inflammatory Agents,Agent, Aspirin-Like,Agent, Non-Steroidal Anti-Inflammatory,Agent, Nonsteroidal Anti-Inflammatory,Anti-Inflammatory Agent, Non-Steroidal,Anti-Inflammatory Agent, Nonsteroidal,Anti-Inflammatory Analgesics,Aspirin Like Agent,Aspirin Like Agents,Non Steroidal Anti Inflammatory Agent,Non Steroidal Anti Inflammatory Agents,Nonsteroidal Anti Inflammatory Agent,Nonsteroidal Anti Inflammatory Agents,Nonsteroidal Antiinflammatory Agents

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