Chronic nerve growth factor administration increases the peripheral exocytotic activity of capsaicin-sensitive cutaneous neurons. Neurosci Lett 2006 Aug 07;403(3):305-8
Date
06/17/2006Pubmed ID
16777323DOI
10.1016/j.neulet.2006.05.020Scopus ID
2-s2.0-33745893566 (requires institutional sign-in at Scopus site) 24 CitationsAbstract
Nerve growth factor (NGF) plays an important role in inflammation and pain and has been suggested to regulate the responsiveness and sensitivity of nociceptive fibers. However, no study has evaluated whether chronic NGF alters the exocytotic capacity of peripheral terminals of peptidergic fibers. To test this hypothesis, rats were injected subcutaneously every other day with either murine recombinant NGF (mNGF; 1.0 mg/kg) or vehicle for 7 days; or mNGF (0.1 mg/kg), mNGF (1 mg/kg) or vehicle every other day for 13 days. Treatment of rats with NGF over a 13-day period produced a significant increase in capsaicin-evoked iCGRP release from isolated biopsies of hindpaw skin, as assessed by in vitro superfusion and RIA. This effect was dose-dependent and exhibited a temporal requirement, because the enhancement was only observed after 13 days of treatment and was not evident after 7 days of treatment. This NGF enhancement of capsaicin-evoked iCGRP release was not due solely to increases in peripheral iCGRP content since only the 1mg/kg dose of NGF elevated cutaneous pools of iCGRP, whereas both doses significantly increased capsaicin-evoked peptide release. Moreover, NGF also enhanced capsaicin-evoked thermal hyperalgesia under similar dose- and time-related conditions. Collectively, the chronic administration of NGF not only increases capsaicin-evoked hyperalgesia, but also significantly primes peripheral fibers to enhanced peptidergic exocytosis following activation of the capsaicin receptor. Collectively, these data are consistent with the hypothesis that persistently elevated NGF levels may contribute to enhanced neurogenic regulation of inflammatory and wound healing processes in injured tissue.
Author List
Bowles WR, Sabino M, Harding-Rose C, Hargreaves KMMESH terms used to index this publication - Major topics in bold
AnimalsCalcitonin Gene-Related Peptide
Capsaicin
Dose-Response Relationship, Drug
Exocytosis
Hot Temperature
Hyperalgesia
In Vitro Techniques
Injections, Subcutaneous
Male
Nerve Endings
Nerve Growth Factor
Neurogenic Inflammation
Neurons
Rats
Rats, Sprague-Dawley
Skin
