PERIPHERAL CELL-TYPES CONTRIBUTING TO THE HYPERALGESIC ACTION OF NERVE GROWTH-FACTOR IN INFLAMMATION

The contribution of nerve growth factor (NGF) to inflammatory hyperalg esia potentially could be mediated by any of the three peripheral cell types that express trkA, the high-affinity NGF receptor: inflammatory cells, sympathetic neurons, and primary sensory neurons. To investiga te their relative involvement, the effects of sympathectomy and mast c ell degranulation were examined on the local inflammation produced by an intraplantar injection of complete Freund's adjuvant in the adult r at. Sympathectomy, produced by neonatal guanethidine treatment, elevat ed basal NGF levels in the skin but did not attenuate a further increa se in NGF during inflammation. Although the onset of inflammatory hype ralgesia was delayed in sympathectomized animals, peak sensitivity was not affected and was still NGF-dependent, In contrast, mast cell degr anulation produced by several days of treatment with the cationic secr etagogue compound 48/80, while also increasing basal NGF levels, preve nted a further increase in NGF levels and attenuated hypersensitivity during inflammation. Neither manipulation modified the inflammatory up regulation of interleukin-1 beta. We conclude that sympathetic neurons contribute transiently to inflammatory hyperalgesia, but that mast ce lls and sensory neurons are important sites for the sustained action o f NGF in producing increased sensitivity during inflammation.