Y the action of inflammatory mediators such as bradykinin (BK) and
Y the action of inflammatory mediators such as bradykinin (BK) and prostaglandins on the primary afferent neurons that express receptors for these compounds in their sensory endings [5,6]. Subgroups of primary afferent neurons also express receptors for neuropeptides such as substance P (SP) that are released from primary afferent fibres. Because the activation of primary afferent neurons by mediators is dependent on the receptors located on the neurons, we investigated in the present experiments the expression of BK and SP [neurokinin 1 (NK1)] receptors in primary afferent neurons in the acute and chronic phases of antigen-induced arthritis (AIA), which resembles in many aspects the inflammatory process of human rheumatoid arthritis [7?0]. BK is a potent pain-producing substance in animals and in humans. When it is applied to the tissue it causes many neurons to fire action potentials, and it sensitizes the neurons so that they respond more strongly to mechanical and thermal stimuli [3,5,11?3]. BK is produced under inflammatory conditions from a precursor and is released in the plasma; it is contained in inflammatory exudates, for example in the joint [14?7]. It acts on BK 2 (B2) receptors that are expressed in sensory neurons under normal conditions. Under inflammatory conditions an additional expression of a BK 1 (B1) receptor has been reported [6,18,19]. SP is a peptide that is produced in and released from the primary afferent fibres themselves. Indeed, SP is synthesized in 10?0 of the primary afferent neurons [20,21], most of which seem to be nociceptive neurons with high thresholds [22]. SP is transported from the cell bodies in the dorsal root ganglia (DRGs) to the sensory endings in the tissue, and the release from the sensory endings causes a neurogenic inflammation [23?5]. SP is also transported to the central order Enasidenib terminals of the primary afferent neurons. At this site it is involved in the activation and in the generation of inflammation-evoked hyperexcitability of spinal cord neurons [26?9]. SP acts on NK1 receptors [30?3]. The application of SP to the tissue can sensitize a proportion of the nociceptive primary afferent neurons, suggesting that SP contributes to the generation of hyperalgesia [34,35]. However, other studies have failed to show effects of SP on primary afferent neurons [36,37]. Thus, under normal conditions, the role of SP is questionable.Arthritis ResearchVol 2 NoSegond von Banchet et alBecause it is very difficult to study PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/26437915 the expression of peptide receptors in situ, we took advantage of the fact that peptide receptors are expressed not only in the terminals of the primary afferent units but also in the cell bodies [33,38?0]. We therefore removed DRGs of both sides from control rats and from rats with the acute or chronic phase of AIA and determined, after short-term culture of the neurons, the proportion of DRG neurons that expressed the receptors under the different experimental conditions. We also characterized the inflammatory process and the nociceptive behaviour of the rats in the course of AIA.Histology and grading of arthritisMaterials and methodsInduction of joint inflammationIn 33 female Lewis PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28192408 rats 10 weeks old (Charles River, Sulzfeld, Germany), an inflammation was induced in the right knee joint. In the first step the rats received a subcutaneous injection of 500 of antigen [methylated bovine serum albumin (m-BSA); Sigma, Deisenhofen, Germany] in 500 of saline and emulsified with 500 of Fre.