INTRAPLANTAR INJECTION OF NERVE GROWTH-FACTOR INTO THE RAT HIND PAW -LOCAL EDEMA AND EFFECTS ON THERMAL NOCICEPTIVE THRESHOLD

Nerve growth factor (NGF) is known to produce hyperalgesia as well as to stimulate synthesis of neuropeptides in dorsal root ganglia (DRG). In the present study, we wanted to determine the effects of local NGF administration and assess to which extent mast cell-dependent factors are mediating NGF responses. Rats received 1 daily unilateral intrapla ntar injection for 3 days. Local edema (days 1-3), changes in thermal nociceptive threshold (days 1-4), and the content of calcitonin gene-r elated peptide (CORP) and substance P (SP) in the sciatic nerve (day 4 ), were determined. NGF injection caused edema which was absent in rat s pretreated with compound 48/80 as well as in rats treated neonatally with capsaicin ('capsaicin denervation'). NGF-induced edema was not r educed by the neurokinin-l receptor antagonist SR140333, but attenuate d by the CORP receptor antagonist CGRP[8-37]. On each day, NGF injecti on caused a decrease in thermal nociceptive threshold which lasted for less than 3 h. Capsaicin-denervation, but not treatment with indometh acin, abolished NGF-induced thermal hyperalgesia. Treatment with compo und 48/80 attenuated hyperalgesia produced by the first, but not by su bsequent, NGF injections. On day 4, 24 h after the last of 3 NGF injec tions, thermal nociceptive threshold was not different from control va lues, but at that time, CGRP and SP were elevated in the sciatic nerve . We suggest therefore that NGF-induced local edema was caused by mast cell-derived vasoactive compounds which act together with afferent ne uron-derived CORP to increase vascular permeability. NGF-induced therm al hyperalgesia most likely was caused by an increased sensitivity of peripheral endings of capsaicin sensitive afferents. This effect of NG F was not mediated by products of the cyclooxygenase pathway, and was also observed in mast cell-depleted rats.