The Journal of Neuroscience, November 1994, 14(11): 6423-6434

Expression of Y and (Y 1) mRNA in Rat Spinal Cord and Dorsal Root Ganglia following Peripheral Tissue Inflammation

Ru-Rong Ji,’ X. Zhang,’ Z. Wiesenfeld-Hallin,2 and T. HiikfelV ‘Department of Neuroscience, Karolinska Institute, S-17177 Stockholm, Sweden and ‘Department of Laboratory Medical Science and Technology, Section of Neurophysiology, Huddinge University Hospital, Stockholm, Sweden S-17177

By using in situ hybridization histochemistry and imrnuno- Injection of complete Freund’s adjuvant (CFA), carrageenan, histochemistry, neuropeptide Y (NPY) and NPY (Y 1) receptor formalin, or other irritative chemicalsinto the hindpaw of the niRNA as well as NPY-like irnmunoreactivity were examined rat producesan intense inflammation characterized by erythe- in the lumbar spinal cord (L4-L5) and in dorsal root ganglia ma, edema,and hyperthermia that is limited to the injected paw (DRG, L5) in rats injected with complete Freund’s adjuvant (Iadarola et al., 1988; Dubner and Ruda, 1992; Solodkin et al., (CFA) into the hindpaw. A rapid and marked increase in NPY 1992; Weihe et al., 1993). Inflammatory tissue produces an rnRNA expression was observed in ipsilateral dorsal horn increasedsensitivity to noxious stimulation (hyperalgesia),and neurons 6 hr after inoculation as compared to the contra- even innocuous stimuli are often perceived as painful. Accom- lateral side. This was mainly found in the medial part of spinal panying thesebehavioral changesare alterations in the discharge lamina II. The peak level (66% increase) was reached at 3 properties ofafferent fibers and neuronsin the CNS (Neugebauer d. In adjacent sections of the spinal cord, 96% and 33% and Schaible, 1990; Dubner and Ruda, 1992), aswell aschanges increases were found in the number of dynorphin and en- in levels of messengermolecules. Thus, it has been shown that kephalin mRNA-positive neurons, respectively. Unilateral in- peripheral inflammation induces upregulation of the synthesis flammation also induced a moderate increase in NPY-like of opioid (Iadarola et al., 1988; Noguchi et al., 1988; immunoreactivity and the number of NPY-immunoreactive Ruda et al., 1988; seealso Dubner and Ruda, 1992; Weihe et neurons in the medial part of the ipsilateral spinal dorsal al., 1993), substanceP (SP) (Noguchi et al., 1988) horn. In addition, a marked elevation in the expression of gene-related (CGRP) (Haneschet al., 1993), glutamate c-Fos-like protein was observed in ipsilateral spinal neurons (Sluka et al., 1992), NADPH-diaphorase (Solodkin et al., 1992), in laminae I, II, and V. However, no NPY mRNA-positive or GABA (Castro-Lopes et al., 1992) and (Tokunaga et NPY-immunoreactive neurons were found in the ipsilateral al., 1992). Unilateral inflammation also evokes an increasein and contralateral DRGs in rats receiving CFA injection. Fur- the dorsal horn expressionof c-j& proto-oncogene (Hunt et al., thermore, a marked upregulation of NPY (Y 1) receptor mRNA 1987; Presley et al., 1990; Noguchi et al., 1991; Hylden et al., expression was detected in the ipsilateral spinal dorsal horn 1992; Leah et al., 1992). 1 d and 3 d after inoculation. These Yl receptor mRNA- With the recent cloning of an increasing number of neuro- positive cells were mainly distributed in the medial laminae peptide receptor genes(Meyerhof et al., 1993), it is now possible II and Ill. Numerous Y 1 mRNA-positive, small neuron profiles to determine the site of synthesisof thesereceptors at the cellular were found bilaterally in the DRGs in CFA-treated rats. CFA level. Indeed, inflammation has been shown to induce an ele- evoked a 34% incr