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.