Involvement of substance P, CGRP and histamine in the hyperalgesia and cytokine upregulation induced by intraplantar injection of capsaicin in rats.
Intraplantar (i.pl.) injection of small doses of capsaicin has been shown to produce hyperalgesia and upregulation of the levels of proinflammatory cytokines. The present work aimed at investigating the possible mediation of these effects by sensory neuropeptides and mast cells. Various groups of rats received i.pl. injection of capsaicin alone or preceded by the injection of antagonists to substance P (SP), calcitonin gene-related protein (CGRP) and histamine (H1, H2) or the mast cell blocker ketotifen. All pretreatments prevented, in a dose-related manner, the capsaicin-induced hyperalgesia. The SP, H2 antagonists and ketotifen prevented the upregulation of all cytokines and nerve growth factor (NGF) levels, while the CGRP and H1 antagonists showed only attenuation of the NGF level.
Massaad
C A
CA
Neuroscience Program, Faculties of Medicine and Arts and Sciences, American University of Beirut, Beirut, Lebanon.
Safieh-Garabedian
B
B
Poole
S
S
Atweh
S F
SF
Jabbur
S J
SJ
Saadé
N E
NE
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000502:physiology*; D002211:Capsaicin / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006632:Histamine / Q000502:physiology*; D006633:Histamine Antagonists / Q000494:pharmacology; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism*; D007278:Injections, Spinal / Q000379:methods; D020932:Nerve Growth Factor / Q000378:metabolism; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D013373:Substance P / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
D000700:Analgesics; D016207:Cytokines; D006633:Histamine Antagonists; C065446:spantide II; D013373:Substance P; D006632:Histamine; D020932:Nerve Growth Factor; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin