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Involvement of spinal substance P and excitatory amino acids in inflammatory hyperalgesia in rats. 1998

K Okano, and Y Kuraishi, and M Satoh
Department of Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.

To reveal possible involvement of NK-1 substance P receptors and N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors in the production of inflammatory hyperalgesia, we examined the effects of intrathecal injections of antagonists at those receptors on the nociceptive threshold of inflammatory hyperalgesic rats in the paw-pressure test. Intrathecal injections of the NK-1 antagonist CP-96,345 (0.3-3 nmol/rat), the NMDA antagonist D-2-amino-5-phosphonovaleric acid (D-APV, 1-10 nmol/rat), and the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 1-10 nmol/rat) dose-dependently suppressed adjuvant- and carrageenin-induced hyperalgesia, without effect on the nociceptive threshold of non-inflamed paws. Furthermore, to estimate whether inflammatory hyperalgesia is accompanied with an alteration of the responsiveness to substance P and excitatory amino acids, we examined the effects of injections of complete Freund's adjuvant (intradermal) and carrageenin (subcutaneous) on the aversive responses to intrathecal substance P and excitatory amino acid agonists. Both injections significantly potentiated the aversive behaviors elicited by intrathecal injections of excitatory amino acid agonists, NMDA (1 nmol/rat), a-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA, 1 nmol/rat) and kainate (1 nmol/rat), but not those by substance P. The present results suggest that the enhancement of synaptic transmission mediated by substance P and excitatory amino acids in the spinal dorsal horn is at least partly involved in the production of inflammatory hyperalgesia, and that such a hyperalgesia is accompanied with the enhanced responsiveness to excitatory amino acids through NMDA and non-NMDA receptors, but not with changes in responsiveness to substance P.

UI MeSH Term Description Entries
D008297 Male Males
D002351 Carrageenan A water-soluble extractive mixture of sulfated polysaccharides from RED ALGAE. Chief sources are the Irish moss CHONDRUS CRISPUS (Carrageen), and Gigartina stellata. It is used as a stabilizer, for suspending COCOA in chocolate manufacture, and to clarify BEVERAGES. Carrageenin,iota-Carrageenan,kappa-Carrageenan,lambda-Carrageenan,iota Carrageenan,kappa Carrageenan,lambda Carrageenan
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
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
D001713 Biphenyl Compounds Whitish aromatic crystalline organic compounds made up of two conjoined BENZENE rings. Compounds, Biphenyl
D013116 Spinal Cord A cylindrical column of tissue that lies within the vertebral canal. It is composed of WHITE MATTER and GRAY MATTER. Coccygeal Cord,Conus Medullaris,Conus Terminalis,Lumbar Cord,Medulla Spinalis,Myelon,Sacral Cord,Thoracic Cord,Coccygeal Cords,Conus Medullari,Conus Terminali,Cord, Coccygeal,Cord, Lumbar,Cord, Sacral,Cord, Spinal,Cord, Thoracic,Cords, Coccygeal,Cords, Lumbar,Cords, Sacral,Cords, Spinal,Cords, Thoracic,Lumbar Cords,Medulla Spinali,Medullari, Conus,Medullaris, Conus,Myelons,Sacral Cords,Spinal Cords,Spinali, Medulla,Spinalis, Medulla,Terminali, Conus,Terminalis, Conus,Thoracic Cords
D013373 Substance P An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of PAIN, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. Euler-Gaddum Substance P,Hypothalamic Substance P,SP(1-11),Euler Gaddum Substance P,Substance P, Euler-Gaddum,Substance P, Hypothalamic

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