Effect of capsaicin on substance P and nerve growth factor in adjuvant arthritic rats.
We have investigated the effect of capsaicin pretreatment (50 mg kg(-1) s.c.) on substance P, preprotachykinin (PPT) mRNA, and nerve growth factor (NGF), plus its high-affinity receptor, trkA, in adult rats with adjuvant arthritis. Twenty one days after induction of adjuvant arthritis, sciatic nerve levels of substance P were significantly increased whilst there was a small but non-significant increase in gamma-PPT mRNA and substance P in L4/L5 dorsal root ganglia (DRG). NGF levels in sciatic nerve and foot skin as well as DRG trkA mRNA were unaltered after 21 days arthritis suggesting that NGF may not play a role in chronic inflammation. Capsaicin treatment of naive rats significantly reduced substance P in all tissues and NGF levels in the sciatic nerve. In contrast, gamma-PPT mRNA and trkA mRNA expression in DRG were significantly increased after capsaicin treatment. The nervous and skin tissues used in this study were harvested from the same rats in which we had previously shown that capsaicin pretreatment significantly attenuated the severity of arthritis (Cruwys, S.C., Garrett, N.E. and Kidd, B.L., Sensory denervation with capsaicin attenuates inflammation and nociception in arthritic rats, Neurosci. Lett., 193 (1995) 205-207). Arthritis in capsaicin-treated rats had no effect on substance P or NGF levels in any tissue when compared with capsaicin-treated control rats, suggesting that pharmacological impairment of the sensory nervous system can reduce the severity of inflammatory joint disease.
Garrett
N E
NE
Department of Pharmacology, St. Bartholomew's and the Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, UK. neil.garrett@blacksci.co.uk
Cruwys
S C
SC
Kidd
B L
BL
Tomlinson
D R
DR
D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000378:metabolism*; D008297:Male; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D011498:Protein Precursors / Q000096:biosynthesis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis; D012016:Reference Values; D012584:Sciatic Nerve / Q000378:metabolism*; D012867:Skin / Q000378:metabolism; D013373:Substance P / Q000096:biosynthesis*; D015320:Tachykinins / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects*
D009414:Nerve Growth Factors; D011498:Protein Precursors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D015320:Tachykinins; C044206:preprotachykinin; D013373:Substance P; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA; D002211:Capsaicin