Hyperalgesia induced in the rat by the amino-terminal octapeptide of nerve growth factor.

Abstract

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-PheHis). 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 i jured target regions of NGF-responsive neurons.

Morphological and Functional Roles of Macrophages and Postganglionic Sympathetic Fibers in Dorsal Root Ganglions of a Rat Neuropathic Pain Model.

“…There are changes in plasma cytokines following peripheral nerve injury [44]. Recent reports demonstrated that IL-1 stimulates Schwann cells to express NGF on their surfaces, and that NGF or an octapeptide of NGF induces pain when injected peripherally [22,42] . TNF-a was shown to induce axonal degeneration when injected into rat nerves [35], and the inhibition of TNF-a by thalidomide reduced the hyperalgesia associated with the chronic constriction injury of the sciatic nerve [39].…”

Activin Induces Tactile Allodynia and Increases Calcitonin Gene-Related Peptide after Peripheral Inflammation

“…Increased NGF contributes to hyperalgesia seen after inflammation (Lembeck et al, 1981;Taiwo et al, 1991;Donaldson et al, 1992;Davis et al, 1993;Lewin et al, 1993;Lewin and Mendell, 1994). For example, systemic NGF administration increases neuropeptides in sensory ganglia (Otten and Lorez, 1982) as well as mechanical and thermal hyperalgesia .…”

A Study to Investigate Tanezumab in Patients with Interstitial Cystitis/Painful Bladder Syndrome

“…Tanezumab is an anti-nerve-growth factor (NGF) agent or monoclonal antibody against NGF that blocks the effects of NGF. It has demonstrated effective and potent analgesic effects in animal models and humans [2][3][4]. The FDA termination of this apparently effective pain-relieving drug is due to a high incidence of avascular necrosis leading to surgical treatment.…”