Abstract
The influence of adjuvant-induced arthritis of the rat on central and peripheral peptide neuroanatomy was investigated by immunohistochemistry. The most striking feature of arthritic rats was the differential intensification of neuronal proenkephalin- and prodynorphin-related staining in dorsal horn. Changes were ipsilateral in monoarthritic and bilateral in polyarthritic rats as compared to controls. Opioid responsive neurons were target of substance P (SP) and calcitonin gene-related peptide (CGRP) fibers. Changes of SP and CGRP predominated in peripheral inflamed tissue and consisted of intensified immunostaining and an apparent sprouting of sensory fibers particularly around venules, in the epidermis and in areas infiltrated by immunocompetent cells. Opioid staining was absent from primary afferents but present in some immune cells of inflamed tissue. Endogenous antinociceptive opioids and pro-nociceptive/pro-inflammatory SP and CGRP may be crucial in the concerted response of the neuroimmune system to chronic inflammatory pain.
Similar content being viewed by others
References
M. J. Millan, M. H. Millan, A. Czlonkowski, V. Höllt, C. W. T. Pilcher, A. Herz and F. C. Colpaert,A model of chronic pain in the rat: response of multiple opioid systems to adjuvant-induced arthritis. J. Neurosci.6, 899–906 (1986).
R. Oku, M. Sato and H. Tagaki,Release of substance P from the spinal dorsal horn is enhanced in polyarthritic rats. Neurosci. Lett.74, 315–319 (1987).
M. Lotz, D. A. Carson and J. H. Vaughan,Substance P activation of rheumatoid synoviocytes: neural pathway in pathogenesis of arthritis. Science235, 893–895 (1987).
V. Höllt, I. Haarmann, M. J. Millan and A. Herz,Prodynorphin gene expression is enhanced in the spinal cord of chronic arthritic rats. Neurosci. Lett.73, 90–94 (1987).
E. Faccini, H. Uzumaki, S. Govoni, C. Missale, P. F. Spano, V. Covelli and M. Trabucchi,Afferent fibers mediate the increase of met-enkephalin elicited in rat spinal cord by localized pain. Pain18, 25–31 (1984).
E. Weihe, M. J. Millan, V. Höllt, D. Nohr and A. Herz,Induction of the gene encoding prodynorphin by experimentally induced arthritis enhances staining for dynorphin in the spinal cord of rats. Neuroscience (in press).
E. Weihe, M. J. Millan, A. Leibold, D. Nohr and A. Herz,Co-localization of proenkephalin- and prodynorphin-derived opioid peptides in laminae IV/V spinal neurons revealed in arthritic rats. Neurosci. Lett.85, 187–192 (1988).
M. A. Ruda, M. J. Iadarola, L. V. Cohen and W. S. Young,In situ hybridization histochemistry and immunocytochemistry reveal an increase in spinal dynorphin biosynthesis in a rat model of peripheral inflammation and hyperalgesia. Proc. Nat. Acad. Sci. USA85, 622–626 (1988).
I. Zachary, P. J. Woll and E. Rozengurt,A role of neuropeptides in the control of cell proliferation. Develop. Biology124, 295–308 (1987).
D. G. Payan, J. P. McGillis, F. K. Renold, M. Mitsuhashi and E. J. Goetzl,Neuropeptide modulation of leukocyte function. Ann. New York Acad. Sci.496, 183–191 (1987).
E. M. Smith, D. V. Harbour and J. E. Blalock,Leukocyte production of endorphins. Ann. New York Acad. Sci.496, 193–195 (1987).
C. Stein, M. J. Millan, T. S. Shippenberg and A. Herz,Peripheral effect of fentanyl upon nociception in inflamed tissue of the rat. Neurosci. Lett.84, 225–228 (1988).
J. L. Joris, R. Dubner and K. M. Hargreaves,Opioid analgesia at peripheral sites: A target for opioids released during stress and inflammation? Anesth. Analg.66, 1277–1281 (1987).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Weihe, E., Nohr, D., Millan, M.J. et al. Peptide neuroanatomy of adjuvant-induced arthritic inflammation in rat. Agents and Actions 25, 255–259 (1988). https://doi.org/10.1007/BF01965027
Issue Date:
DOI: https://doi.org/10.1007/BF01965027