In vivo pain-inhibitory role of nociceptin/orphanin FQ in spinal cord.

Content Provider	Semantic Scholar
Author	Inoue, Makoto Kawashima, Toshiko Takeshima, Hiroshi Calo, Girolamo Inoue, Atsuko Nakata, Yoshihiro Ueda, Hiroshi
Copyright Year	2003
Abstract	Because nociceptin/orphanin FQ (N/OFQ) has both pronociceptive (hyperalgesia) and antinociceptive actions in pharmacological experiments, and there is no significant difference in the nociceptive responses between NOP(-/-) mice and their wild-type (NOP(+/+)) littermates, the physiological role of N/OFQ in pain regulation remains to be determined. Under the hypothesis that the use of molecularly distinct nociception test may reveal the pain modality-specific role of N/OFQ, we attempted to examine the physiological role of N/OFQ in pain transmission by using newly developed algogenic-induced nociceptive flexion test in NOP(-/-) and NOP(+/+) mice or NOP antagonist-treated mice. The nociceptive flexor responses upon intraplantar injection of bradykinin or substance P, which stimulates polymodal substance P-ergic fibers, were markedly potentiated in NOP(-/-) mice, compared with those in its NOP(+/+) mice. However, there were no significant changes in NOP(-/-) mice with adenosine triphosphate or prostaglandin I(2) agonist, which stimulates glutamatergic but not substance P-ergic fibers. The nocifensive responses induced by substance P (i.t.) were also potentiated in NOP(-/-) mice. On the other hand, there were no significant differences in NK1-like immunoreactivity, [(3)H]substance P binding, or NK1 gene expression in the dorsal horn of the spinal cord between NOP(-/-) and NOP(+/+) mice. In addition, NOP antagonists decreased the threshold in nociception tests driving spinal substance P neurotransmission. All these findings suggest that the N/OFQ-ergic neuron may play an in vivo inhibitory role on the second-order neurons for primary polymodal substance P-ergic fibers in the spinal cord.
Starting Page	495
Ending Page	501
Page Count	7
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://jpet.aspetjournals.org/content/jpet/305/2/495.full.pdf
PubMed reference number	12606680v1
Volume Number	305
Issue Number	2
Journal	The Journal of pharmacology and experimental therapeutics
Language	English
Access Restriction	Open
Subject Keyword	Adenosine Triphosphate Alprostadil Attempt Bradykinin Gene Expression Hyperalgesia Neurons Nociceptin, human Nociception PNOC wt Allele Pain Measurement Pharmacology Prostaglandin Antagonists Prostaglandins Spinal cord posterior horn Structure of posterior gray horn of spinal cord Synaptic Transmission Tissue fiber gamma-Aminobutyric Acid-ergic Agonist [EPC] nociceptin receptor
Content Type	Text
Resource Type	Article