Hyperalgesia induced in the rat by the amino-terminal octapeptide of nerve growth factor.
Nerve growth factor (NGF) in the mouse submandibular gland undergoes cleavage of its amino-terminal octapeptide when salivation is induced by epinephrine. The significance of this event is uncertain; cleaved NGF demonstrates bioactivity and no function has been attributed to the octapeptide produced (NGF-OP; Ser-Ser-Thr-His-Pro-Val-Phe-His). Enzyme inhibition studies indicating structural relatedness of NGF-OP and bradykinin (BK) prompted us to determine whether NGF-OP would elicit BK-like actions. We found that like BK, NGF-OP induced a decrease in mechanical nociceptive threshold (i.e., produced hyperalgesia) in the hairy skin of the rat. This effect was dose-dependent and sequence-specific; like BK it was attenuated by sympathectomy and indomethacin pretreatment. However, NGF-OP actions appeared to be distinct from those for BK in that tissue injury was required for NGF-OP to induce hyperalgesia. Furthermore, we found no evidence that NGF-OP bound to or activated BK receptors. Our data indicate that NGF-OP is a distinct mediator of hyperalgesia. We suggest that NGF-OP alters pain threshold in the injured target regions of NGF-responsive neurons.
Taiwo
Y O
YO
Neuroscience Program, University of California, School of Medicine, San Francisco 94143.
Levine
J D
JD
Burch
R M
RM
Woo
J E
JE
Mobley
W C
WC
D000818:Animals; D001920:Bradykinin / Q000378:metabolism; D006930:Hyperalgesia / Q000139:chemically induced*; D008297:Male; D009414:Nerve Growth Factors / Q000494:pharmacology*; D010146:Pain / Q000139:chemically induced; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D012684:Sensory Thresholds / Q000187:drug effects
D009414:Nerve Growth Factors; D010455:Peptides; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D001920:Bradykinin