Modulation of NMDA receptors by intrathecal administration of the sensory neuron-specific receptor agonist BAM8-22.
The sensory neuron-specific receptor (SNSR) is exclusively distributed in dorsal root ganglion (DRG) cells. We have demonstrated that intrathecal (i.t.) administration of SNSR agonists inhibits formalin-evoked responses and the development of morphine tolerance [Chen, T., Cai, Q., Hong, Y., 2006. Intrathecal sensory neuron-specific receptor agonists bovine adrenal medulla 8-22 and (tyr(6))-gamma2-msh-6-12 inhibit formalin-evoked nociception and neuronal fos-like immunoreactivity in the spinal cord of the rat. Neuroscience 141, 965-975]. The present study was undertaken to examine the possible impact of the activation of SNSR on NMDA receptors. I.t. administration of NMDA (6.8 nmol) induced nociceptive behaviors, including scratching, biting and lifting, followed by thermal hypoalgesia and hyperalgesia. These responses were associated with the expression of Fos-like immunoreactivity (FLI) throughout the spinal dorsal horn with highest effect seen in laminae I-II. I.t. NMDA also induced an increase in nitric oxide synthase (NOS) activity in superficial layers of the dorsal horn, but not around the central canal, as revealed by NADPH diaphorase histochemistry. Pretreatment with the SNSR agonist bovine adrenal medulla 8-22 (3, 10 and 30 nmol) dose-dependently diminished NMDA-evoked nocifensive behaviors and hyperalgesia. This agonist also reduced NMDA-evoked expression of FLI and NADPH reactivity in the spinal dorsal horn. Taken together, these data suggest that the activation of SNSR induces spinal analgesia by suppressing NMDA receptor-mediated activation of spinal dorsal horn neurons and an increase in NOS activity.
Chen
Tingjun
T
College of Life Sciences and Provincial Key Laboratory of Developmental Biology Neuroscience, Fujian Normal University Fuzhou, Fujian 350108, People's Republic of China.
Hu
Zhijing
Z
Quirion
Rémi
R
Hong
Yanguo
Y
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000009:adverse effects; D005557:Formaldehyde; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D016202:N-Methylaspartate / Q000009:adverse effects; D009249:NADP / Q000378:metabolism; D010146:Pain / Q000139:chemically induced / Q000378:metabolism*; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000737:chemistry* / Q000502:physiology
D018690:Excitatory Amino Acid Agonists; D018160:Receptors, Cytoplasmic and Nuclear; D016194:Receptors, N-Methyl-D-Aspartate; D005557:Formaldehyde; D009249:NADP; D016202:N-Methylaspartate