Modulation of nociceptive transmission by pituitary adenylate cyclase activating polypeptide in the spinal cord of the mouse.
Superficial layers of the dorsal horn receive a dense plexus of nerve fibers immunoreactive to pituitary adenylate cyclase activating polypeptide (PACAP). In vivo experiments were conducted in the mice to evaluate the effects of PACAP-38, herein referred to as PACAP, PACAP receptor antagonist PACAP(6-38) and PACAP-antiserum on nociceptive behaviors induced by radiant heat, intrathecally administered N-methyl-D-aspartate (NMDA) or intraplantarly administered formalin. PACAP (0.05-0.5 microg) dose-dependently decreased the paw-withdrawal latencies induced by thermal stimulation and enhanced the aversive licking and biting behaviors induced by intrathecally injected NMDA. Pretreatment with the PACAP receptor antagonist PACAP(6-38) (0.5-2 microg) or PACAP-antiserum (1:500-2,000 dilution) dose-dependently attenuated the second phase, but not the first phase, of nociceptive responses to formalin. Next, the effects of PACAP on NMDA- and kainate-induced currents evoked in single dorsal horn neurons were studied. Whole-cell patch recordings were made from superficial dorsal horn neurons of spinal cord slices from 14- to 20-day-old mice. PACAP at the concentrations of 100 and 200 nM, which caused no significant change of holding currents, increased NMDA-but not kainate-induced currents in superficial dorsal horn neurons. Our results suggest that exogenously applied PACAP sensitizes the dorsal horn neurons to formalin stimulation, and facilitates NMDA receptor-mediated nociceptive response. As a corollary, PACAP, which may be released from primary afferent fibers potentiates nociceptive transmission to the dorsal horn by interacting primarily with NMDA receptors.
Ohsawa
Masahiro
M
Department of Anesthesiology, Medical Education Building-Room M4330, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Brailoiu
G Cristina
GC
Shiraki
Maho
M
Dun
Nae J
NJ
Paul
Kirstein
K
Tseng
Leon F
LF
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D006358:Hot Temperature; D007278:Injections, Spinal; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D016202:N-Methylaspartate / Q000494:pharmacology; D009475:Neurons, Afferent / Q000502:physiology; D009479:Neuropeptides / Q000276:immunology / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D013376:Substantia Gelatinosa / Q000166:cytology / Q000502:physiology*
C495402:Adcyap1 protein, mouse; D000906:Antibodies; D018690:Excitatory Amino Acid Agonists; D009479:Neuropeptides; D010446:Peptide Fragments; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; C075647:pituitary adenylate-cyclase-activating-peptide (6-38); D016202:N-Methylaspartate