Effects of capsaicin in temporomandibular joint arthritis in rats.

Temporomandibular joint (TMJ) arthritis was induced in female Lewis rats by unilateral injection of a suspension of heat-killed Mycobacterium butyricum in paraffin oil into the TMJ. Control rats received paraffin oil by the same route. Arthritic and control rats were pretreated either with capsaicin or denervation of the mandibular branch of the trigeminal nerve. Tissues were collected for neuropeptide extraction and analysed by radioimmunoassay and reverse-phase high-performance liquid chromatography. In all groups, the levels of substance P-(SP), calcitonin gene-related peptide- (CGRP) and neuropeptide Y- (NPY) like immunoreactivity (LI) were higher in the trigeminal ganglia than in the TMJs. In control rats, capsaicin significantly lowered the levels of SP-LI in the trigeminal ganglia and TMJ, but not CGRP-LI and NPY-LI. In the arthritic rats, capsaicin pretreatment significantly lowered the SP-LI and CGRP-LI in the trigeminal ganglia and TMJ, but not the NPY-LI. In the trigeminal ganglia the unilateral denervation significantly lowered SP-LI in control rats, and in arthritic rats SP-LI and CGRP-LI. On the denervated side of the arthritic TMJ, NPY-LI, SP-LI and CGRP- LI were significantly lowered as compared to the arthritic control rats and to the contralateral side. In this rat model, pretreatment with capsaicin and surgical denervation decreased the neuropeptide content in the trigeminal ganglia and the TMJ. The results clearly demonstrate a close interaction between increased neuropeptide release from sensory and sympathetic neurones after induction of arthritis in the rat.

Substance P-, neurokinin A-, calcitonin gene-related peptide- and neuropeptide Y-like immunoreactivity (-LI) in rat knee joint synovial fluid during acute monoarthritis is not correlated with concentrations of neuropeptide-LI in cerebrospinal fluid and plasma.

In a recent study we have shown a bilateral release of substance P (SP)-, neurokinin A (NKA)-, calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)-like immunoreactivity (-LI) in rat synovial fluid during acute monoarthritis. In order to elucidate the mechanisms underlying these phenomena, we examined the correlation between neuropeptide-LI in rat cerebrospinal fluid (CSF) and synovial fluid and between plasma and synovial fluid following the intra-articular injection of equal volumes (0.05 ml) of either Freund's adjuvans, carrageenan 2%, substance P 10(-5) M or human recombinant interleukin-1 alpha. Control rats were given saline intra-articularly. CSF, plasma and synovial fluid from the knee joints were obtained at 2, 6 and 24 h after injection and were analysed by specific radioimmunoassays. The intra-articular injection of pro-inflammatory substances induced changes in neuropeptide-LI in synovial fluid, CSF and plasma. However, there was no correlation between neuropeptide-LI in synovial fluid and plasma or between synovial fluid and CSF. The results of the present study does not support the hypothesis that the bilateral changes in neuropeptide-LI in synovial fluid were due to a release of neuropeptides from the inflamed joint into the systemic circulation. However, in carrageenan induced inflammation there was a tendency towards a correlation in SP-LI between CSF and synovial fluid suggesting that central neurogenic mechanisms should be studied in order to explain the bilateral changes seen.

Bilateral changes of substance P-, neurokinin A-, calcitonin gene-related peptide- and neuropeptide Y-like immunoreactivity in rat knee joint synovial fluid during acute monoarthritis.

It has been hypothesized that the nervous system contributes to the symmetrical response in rheumatoid arthritis. In order to elucidate this, the bilateral concentrations of substance P-like immunoreactivity (SP-LI), neurokinin A-LI (NKA-LI), calcitonin gene-related peptide-LI (CGRP-LI) and neuropeptide Y-LI (NPY-LI) in rat synovial fluid during acute monoarthritis were studied. Equal volumes (0.05 ml) of either Freund adjuvants, carrageenan 2%, substance P 10(-5) M or human recombinant interleukin-1 alpha were injected into the right and saline into the left knee joint. Control rats were given saline bilaterally. Perfusates were obtained from both knees simultaneously at 2, 6 and 24 h after injection and were analysed by specific radioimmunoassays. Increase of SP-, NKA-, CGRP- and NPY-LI in synovial fluid occurred in both knees after injections with the pro-inflammatory substances into the right joints as compared to controls, except for unchanged SP-LI in the right knee joint after 24 h following hrIL-1 alpha injection. There was, however, generally no significant difference in the peptide contents between the right knee (injected with pro-inflammatory substance) as compared to the left knee (given saline) at 2, 6 or 24 h after injection except at three occasions. The results show that experimentally induced monoarthritis induces bilateral changes in synovial fluid peptide content.