Neonatal capsaicin treatment attenuates spinal Fos activation and dynorphin gene expression following peripheral tissue inflammation and hyperalgesia.
An animal model of nociception involving unilateral hindpaw inflammation has been used to examine behavioral, molecular, and biochemical aspects of well-characterized spinal cord neural circuits involved in pain transmission. The neurotoxin capsaicin administered neonatally was used to modify this neuronal system by producing a selective destruction of most small, unmyelinated primary afferent axons. Capsaicin had minimal effects on the behavioral hyperalgesia and edema associated with the hindpaw inflammation and on the constitutive expression of preprodynorphin (PPD) mRNA and preproenkephalin mRNA in the spinal cord. However, the inflammation-induced increases in Fos-like immunoreactivity (Fos-LI) and in PPD mRNA were greatly attenuated by neonatal capsaicin treatment. The data indicate that input from small-diameter unmyelinated primary afferents is important for the stimulus-induced increase in Fos-LI and PPD mRNA. Our finding that neonatal capsaicin reduces the levels of Fos-LI and PPD mRNA in a related fashion in the spinal dorsal horn provides further evidence for a relationship between the protein product of the c-fos protooncogene and regulation of dynorphin gene transcription.
Hylden
J L
JL
Neurobiology and Anesthesiology Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892.
Noguchi
K
K
Ruda
M A
MA
D000818:Animals; D000831:Animals, Newborn; D002211:Capsaicin / Q000494:pharmacology*; D004399:Dynorphins / Q000235:genetics* / Q000378:metabolism; D004745:Enkephalins / Q000378:metabolism; D005260:Female; D005534:Foot Diseases / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D006930:Hyperalgesia / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D008297:Male; D011498:Protein Precursors / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism
D004745:Enkephalins; D011498:Protein Precursors; D016760:Proto-Oncogene Proteins c-fos; C036448:pre-prodynorphin; D013373:Substance P; D004399:Dynorphins; C033660:preproenkephalin; D002211:Capsaicin