neuropeptide-y and Temporomandibular-Joint-Disorders

Orofacial pain frequently originates from pathologic conditions in the masticatory muscles or temporomandibular joints (TMJs). The mediators and mechanisms that monitor pain and inflammation, centrally or peripherally, are of great interest in the search for new treatment modalities. The neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP), and neuropeptide Y (NPY) have all been found at high levels in the synovial fluid of arthritic TMJs in association with spontaneous pain, while serotonin (5-HT) has been found in association with hyperalgesia/allodynia of the TMJ. Interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) have been found in arthritic TMJs, but not in healthy TMJs, in association with hyperalgesia/allodynia of the TMJ as well as spontaneous pain. Anterior open bite, which may be a clinical sign of TMJ destruction, has been found in association with high levels of CGRP, NPY, and IL-1 beta in the synovial fluid of the TMJ. Interleukin-1 beta has also been related to radiographic signs of joint destruction. Prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) are both present in the arthritic TMJ, and PGE2 has been shown to be associated with hyperalgesia/allodynia of the TMJ. Very little is known about pain and inflammatory mediators in muscles. However, we know that 5-HT and PGE2 are involved in the development of pain and hyperalgesia/allodynia of the masseter muscle in patients with fibromyalgia, whereas local myalgia (myofascial pain) seems to be modulated by other, as yet unknown mediators. Interaction between the peripheral nervous system (sensory and sympathetic nerves), the immune system, and local cells is probably of great importance for the modulation of pain and inflammation in the TMJ and orofacial musculature.

Topics: Arthritis; Calcitonin Gene-Related Peptide; Dinoprostone; Facial Pain; Fibromyalgia; Humans; Hyperalgesia; Inflammation Mediators; Interleukin-1; Leukotriene B4; Masseter Muscle; Neuroimmunomodulation; Neuropeptide Y; Neuropeptides; Neurosecretory Systems; Open Bite; Serotonin; Substance P; Synovial Fluid; Temporomandibular Joint Disorders; Tumor Necrosis Factor-alpha

This article describes the possible role of various peptides in producing pain and inflammation in the temporomandibular joint (TMJ).. Current research findings on the spectrophotometric quantification of TMJ synovial fluid for neuropeptide Y (NPY), serotonin (5HT), and interleukin-1beta (IL-1beta) are presented.. NPY was found in high levels in the synovial fluid of arthritic TMJs with resting pain, and serotonin (5-HT) was found in patients with pain perceived on mandibular movement. These pain-related mediators were also associated with restricted mandibular mobility. Interleukin-1beta (IL-1beta) was found to be strongly associated with hyperalgesia over the TMJ as well as resting pain. Anterior open bite as a clinical sign of joint destruction was found to be associated with high levels of NPY and IL-1beta in the synovial fluid. IL-1beta was also related to the radiographic signs of joint destruction.. Interaction between the peripheral nervous system (sensory and sympathetic nerves) and the immune system is probably of importance for the modulation of pain and inflammation in the TMJ, but this subject has to be investigated further with experimental clinical studies.

Topics: Animals; Arthritis; Facial Pain; Humans; Inflammation Mediators; Interleukin-1; Neuroimmunomodulation; Neuropeptide Y; Serotonin; Synovial Fluid; Temporomandibular Joint Disorders

To study the effect of experimentally induced osteoarthrosis, or non-inflammatory degenerative changes, on the innervation of the sheep temporomandibular joint (TMJ) through the use of indirect immunohistochemistry and image analysis quantification.. Bilateral condylar scarification was performed in 8 sheep, which were killed at 16 weeks post-operation; 3 unoperated sheep served as controls. Tissues from 8 osteoarthrotic joints and 4 control joints were processed for the immunostaining with antisera for protein gene product 9.5 (PGP 9.5), substance P (SP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), and tyrosine hydroxylase (TH). An additional 10 joints were decalcified to study the morphologic changes induced by the condylar abrasion.. Osteoarthrotic changes were commonly seen in the anterior and lateral regions of the joint and included fibrosis, peripheral osteophyte formation, cysts, and erosion of articular surfaces. In the osteoarthrotic joints, the distribution of PGP 9.5-, CGRP-, and SP-immunoreactive (IR) nerve fibers was similar to that observed for control joints in the capsule, synovium, and capsule/disc junction. There were statistically detectable decreases in the percent surface area of IR nerve fibers in the capsule for both PGP 9.5 and CGRP in arthrotic joints compared with control joints. The lateral and anterior regions of the capsule had greater density of PGP 9.5- and CGRP-IR nerve fibers than other parts of the capsule in both control and arthrotic joints, and the medial capsule was poorly innervated in all joints. Immunostaining for substance P was always weaker.. This study suggests that while inflammatory arthritis has a marked influence on the density of sensory and autonomic nerve fibers in synovium in a variety of joints in different species, experimentally induced non-inflammatory osteoarthrosis in the sheep TMJ also leads to a depletion of the density of nerve fibers in the capsule, especially in the lateral part of the joint. Further work is required to determine whether other parts of the joint, such as synovium and marrow, respond differently to experimentally induced osteoarthrosis.

Topics: Analysis of Variance; Animals; Autonomic Nervous System; Calcitonin Gene-Related Peptide; Cicatrix; Cysts; Disease Models, Animal; Fibrosis; Image Processing, Computer-Assisted; Immunohistochemistry; Joint Capsule; Male; Mandibular Condyle; Nerve Fibers; Nerve Tissue Proteins; Neurons, Afferent; Neuropeptide Y; Osteoarthritis; Sheep; Statistics, Nonparametric; Substance P; Synovial Membrane; Temporomandibular Joint; Temporomandibular Joint Disc; Temporomandibular Joint Disorders; Thiolester Hydrolases; Tyrosine 3-Monooxygenase; Ubiquitin Thiolesterase; Vasoactive Intestinal Peptide

The aim of this study was to test the hypothesis that temporomandibular joint (TMJ) pain is influenced by circulating levels of neuropeptide Y, serotonin, and interleukin-1 beta in rheumatoid arthritis.. Forty-three seropositive (RF+) or seronegative (RF-) rheumatoid arthritis patients and 24 healthy individuals were included in the study.. High serum concentrations of serotonin were associated with low TMJ pressure pain thresholds and pain during mandibular movement in the RF+ patients. The results of this study do not support a relationship between circulating neuropeptide Y or interleukin-1 beta and TMJ pain. The RF+ patients had higher C-reactive protein levels and erythrocyte sedimentation rates than the RF- patients. There were also higher plasma levels of interleukin-1 beta in the RF+ patients than in the healthy individuals. Plasma levels of neuropeptide Y in the RF- patients were higher than in the healthy individuals.. This study indicates that the serum concentration of serotonin is associated with TMJ allodynia in seropositive rheumatoid arthritis.

Topics: Adult; Analysis of Variance; Arthritis, Rheumatoid; Case-Control Studies; Facial Pain; Female; Free Radical Scavengers; Humans; Inflammation Mediators; Interleukin-1; Male; Middle Aged; Neuropeptide Y; Pain Measurement; Rheumatoid Factor; Serotonin; Statistics, Nonparametric; Temporomandibular Joint Disorders

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.

Topics: Animals; Arthritis; Calcitonin Gene-Related Peptide; Capsaicin; Chromatography, High Pressure Liquid; Denervation; Disease Models, Animal; Female; Mandibular Nerve; Neurons, Afferent; Neuropeptide Y; Neurotoxins; Nontuberculous Mycobacteria; Radioimmunoassay; Rats; Rats, Inbred Lew; Substance P; Sympathetic Nervous System; Temporomandibular Joint; Temporomandibular Joint Disorders; Trigeminal Ganglion

To study the role of the nervous system in temporomandibular joint arthritis, substance P-, calcitonin gene-related peptide-, and neuropeptide Y-like immunoreactivity in the trigeminal ganglia and temporomandibular joint of rats was examined. Arthritis was induced in female Lewis rats through bilateral injection of a suspension of heat-killed Mycobacterium butyricum in paraffin oil into the temporomandibular joint. Control rats received paraffin oil via the same route. Tissues were collected for neuropeptide extraction 28 days after injection and analyzed by radioimmunoassay and reverse-phase high-performance liquid chromatography. Calcitonin gene-related peptide was significantly increased in the arthritic trigeminal ganglia. Substance P, calcitonin gene-related peptide, and neuropeptide Y in the arthritic temporomandibular joint were significantly increased as compared to controls. The results of this study show that sensory and sympathetic neuropeptides may possibly be associated with the development of arthritis in the temporomandibular joint of rats.

Topics: Animals; Arthritis, Experimental; Calcitonin Gene-Related Peptide; Chromatography, High Pressure Liquid; Female; Neuroimmunomodulation; Neuropeptide Y; Neuropeptides; Radioimmunoassay; Rats; Rats, Inbred Lew; Substance P; Temporomandibular Joint; Temporomandibular Joint Disorders; Trigeminal Ganglion

Twenty-two patients (29 joints) with temporomandibular joint (TMJ) arthritis of specific or unspecific nature were given one intra-articular glucocorticoid (GC) injection. The effect on subjective symptoms and clinical signs in the craniomandibular system and on joint aspirate concentration of neuropeptide Y-like immunoreactivity (NPY-LI) was evaluated at follow-up visits 2-3 or 4-6 weeks after treatment. In the patients with specific inflammatory joint disease the treatment resulted in an improvement of symptoms and clinical signs and in a reduction in the TMJ level of NPY-LI 2-3 weeks after treatment. In the patients with unspecific inflammatory joint disease there was also an improvement in the clinical variables and a reduction in the NPY-LI level after 2-3 weeks, but not on a statistically significant level. The results of this study show that intra-articular GC treatment causes a short-term decrease of the TMJ fluid level of NPY-LI in patients with specific inflammatory joint disease, while symptoms and signs improve.

Topics: Adult; Anti-Inflammatory Agents; Arthritis; Arthritis, Psoriatic; Arthritis, Rheumatoid; Female; Follow-Up Studies; Humans; Injections, Intra-Articular; Male; Methylprednisolone; Middle Aged; Neuropeptide Y; Pain Measurement; Pain Threshold; Punctures; Synovial Fluid; Temporomandibular Joint Disorders

This is a study of neurokinin A (NKA)-, calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)- like immunoreactivity(-LI) in the cerebrospinal fluid (CSF), plasma and perfusates (PF) from the temporomandibular joints (TMJs) of the rat during acute inflammation. Substance P (10(-5) M, 0.01 ml) was injected into the right TMJ of the rat. The TMJs of the control rats, were injected with 0.01 ml saline. CSF, plasma and PF from TMJs were taken at 2, 6 and 24 hrs following injection. The neuropeptide-LI level was analysed by specific radioimmunoassays and compared with control values. Unilateral injection of SP into the rat TMJ resulted in a general increase in the concentration of NKA-, CGRP- and NPY-LI in the TMJ PF at 2, 6 and 24 hrs following injection. In the CSF NKA- and CGRP-LI was increased leaving the NPY-LI unaffected. In general no changes in peptide concentrations were seen in plasma. The results indicate that SP directly or indirectly induces a local release of peptides through an action at sensory and sympathetic neurons.

Topics: Animals; Calcitonin Gene-Related Peptide; Chromatography, High Pressure Liquid; Disease Models, Animal; Inflammation; Male; Neurokinin A; Neuropeptide Y; Neuropeptides; Rats; Rats, Sprague-Dawley; Substance P; Temporomandibular Joint; Temporomandibular Joint Disorders

To study the interaction between human recombinant interleukin-1 alpha and the nervous system, substance P-, neurokinin A-, calcitonin gene-related peptide-, and neuropeptide Y-like immunoreactivity in the cerebrospinal fluid, plasma, and temporomandibular joint (TMJ) perfusates of rats during acute experimental monarthritis were examined. The right TMJs of the experimental rats were injected with 0.01 mL of human recombinant interleukin-1 alpha. The right TMJs of control rats were injected with 0.01 mL of saline. Cerebrospinal fluid, plasma, and perfusates from the right TMJs were obtained at 2, 6, and 24 hours following injection, and neuropeptide-like immunoreactivity was analyzed by specific radioimmunoassays. Values of neuropeptide-like immunoreactivity for the experimental rats were compared with those of the control rats. In the experimental group, substance P-, neurokinin A-, and calcitonin gene-related peptide-like immunoreactivities were increased in cerebrospinal fluid compared to those of the control group. In plasma, no changes in neuropeptide-like immunoreactivities rose significantly in the TMJ perfusates. Most pronounced changes in neuropeptide Y-like immunoreactivity occurred intra-articularly in the TMJ perfusates. The results indicate that the contribution of the nervous system to human recombinant interleukin-1 alpha-induced monarthritis is most pronounced in the affected joint.

Topics: Animals; Arthritis; Calcitonin Gene-Related Peptide; Humans; Interleukin-1; Male; Neuroimmunomodulation; Neurokinin A; Neuropeptide Y; Neuropeptides; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Substance P; Synovial Fluid; Temporomandibular Joint; Temporomandibular Joint Disorders

Substance P (SP)-, neurokinin A (NKA)-, calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)-like immunoreactivities (-LI) were examined in cerebrospinal fluid (CSF), plasma and temporomandibular joint (TMJ) perfusates in rats 1 and 12 h after inoculation at the base of the tail (0.05 ml) or injection into the right TMJ (0.01 ml) of heat-killed Mycobacterium butyricum in paraffin oil. In the rats inoculated at the base of the tail (polyarthritic rats), there was a significant increase of CGRP-LI and NKA-LI. The changes in neuropeptide-LI were not as marked in the CSF of rats injected with adjuvant in one TMJ (monoarthritic rats) as in the polyarthritic group. Instead, the most significant changes in the monoarthritic rats were seen in the perfusates of both TMJs. The increases in SP-, NKA-, CGRP- and NPY-LI were significant for both TMJs and more pronounced than in the polyarthritic rats. The results show that inoculation of adjuvant at the base of the tail induces significant changes of neuropeptide-LI predominantly in CSF, whilst an intra-articular injection induces bilateral changes in neuropeptide-LI in joint perfusate. Therefore, two different neural mechanisms may be involved early in adjuvant-induced poly- and monoarthritis.

Topics: Animals; Arthritis, Experimental; Bacterial Proteins; Calcitonin Gene-Related Peptide; Immunohistochemistry; Male; Mycobacterium; Neuroimmunomodulation; Neurokinin A; Neuropeptide Y; Neuropeptides; Rats; Rats, Sprague-Dawley; Statistics, Nonparametric; Substance P; Synovial Fluid; Temporomandibular Joint Disorders

Forty-one patients (37 female and four male) with signs and symptoms of temporomandibular joint arthritis, were separated into two diagnostic groups (group I: inflammatory; group II: degenerative/non-specific joint disease). They were examined clinically, fluid was aspirated from the joint with saline and venous blood samples were collected at the same time. The joint fluid and plasma samples were analysed for neuropeptide-like immunoreactivity, i.e. neuropeptide Y (NPY-LI), calcitonin gene-related peptide (CGRP-LI), substance P (SP-LI) and neurokinin A (NKA-LI), using competitive radioimmunoassays. The aim was to investigate any co-variation of the peptides in the joint fluid and plasma. In group I, the median values of peptide concentrations in joint fluid were SP-LI = 129, CGRP-LI = 75, NKA-LI = 36 and NPY-LI = 676 pmol/l and in group II, SP-LI = 52, CGRP-LI = 64, NKA-LI = 45 and NPY-LI = 318 pmol/l. There were no significant differences between the groups for peptide concentrations. In group I, all the neuropeptides were strongly correlated. In group II, SP-LI and NKA-LI were strongly correlated while CGRP-LI was weakly correlated with NPY-LI and NKA-LI. Multiple step-wise regression analysis showed that most of the variation in NPY-LI, CGRP-LI and SP-LI in group I was explained by NKA-LI, but the regression did not reach statistical significance in group II.

Topics: Adult; Aged; Arthritis; Arthritis, Psoriatic; Arthritis, Rheumatoid; Calcitonin Gene-Related Peptide; Female; Humans; Male; Middle Aged; Neurokinin A; Neuropeptide Y; Osteoarthritis; Regression Analysis; Spondylitis, Ankylosing; Substance P; Synovial Fluid; Temporomandibular Joint Disorders

The aim of the investigation was to test the reproducibility and accuracy of a new method to measure temporomandibular joint (TMJ) fluid concentrations of various substances by saline washing, using exogenous B12 as a marker. An in vitro test was first performed with glucose as a test substance. The difference between a B12-calculated and known standard concentration of glucose was very small. Saline washing of the TMJ was performed on 13 patients having signs of TMJ arthritis, and the aspirates obtained were analyzed for neuropeptide Y-like immunoreactivity (NPY-LI) and interleukin-1 beta (IL-1 beta). Vitamin B12 was mixed with the saline immediately before injection, and a sample of the aspirate was later compared photometrically with the injection solution. There were positive correlations between saline aspirate and joint fluid concentrations for NPY-LI and IL-1 beta, and the correlations were stronger for saline aspirates with high joint fluid content. This study shows that the method is reliable for measurement of joint fluid concentrations of various substances, such as NPY-LI and IL-1 beta.

Topics: Arthritis; Female; Glucose; Humans; Interleukin-1; Male; Middle Aged; Neuropeptide Y; Reference Standards; Reproducibility of Results; Sodium Chloride; Spectrophotometry; Suction; Synovial Fluid; Temporomandibular Joint; Temporomandibular Joint Disorders; Therapeutic Irrigation; Vitamin B 12

The contribution of the nervous system to the pathophysiology of rheumatoid arthritis has been proposed to be mediated by certain neuropeptides. Neuropeptide Y, calcitonin gene-related peptide, substance P, and neurokinin A are considered modulators of inflammatory joint disease. Parameters of pain, as well as occlusal signs of tissue destruction from the arthritic TMJ and the corresponding neuropeptide concentrations in TMJ synovial fluid, were investigated in patients with various inflammatory joint diseases. The patients with rheumatoid arthritis were also examined in a separate diagnostic group. Visual analog scale, palpatory tenderness, maximal voluntary mouth opening, and anterior open bite were correlated to neuropeptide-like immunoreactivities of the above four neuropeptides. It was found that high concentrations of calcitonin gene-related peptide and neuropeptide Y in TMJ fluid are associated with pain, impairment of mandibular mobility, and occlusal signs of TMJ destruction in patients with rheumatoid arthritis. The results indicated neuropeptide involvement in rheumatoid arthritis, proposing a potentiation of the symptoms and signs by the inflammatory action of calcitonin gene-related peptide and neuropeptide Y.

Topics: Adult; Arthritis; Arthritis, Rheumatoid; Calcitonin Gene-Related Peptide; Female; Humans; Inflammation Mediators; Male; Middle Aged; Neuroimmunomodulation; Neurokinin A; Neuropeptide Y; Neuropeptides; Pain; Pain Measurement; Range of Motion, Articular; Statistics, Nonparametric; Substance P; Synovial Fluid; Temporomandibular Joint Disorders

Arthritic temporomandibular joints were examined for the joint fluid content of neuropeptide Y-like immunoreactivity (NPY-LI) and the intra-articular temperature at two separate sessions. Sixteen patients (23 joints) with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and unspecific polyarthritis or monarthritis were investigated in this study. The intra-articular temperature ranged between 35.6 and 37.5 degrees C. The concentration of NPY-LI ranged between 72.1 and 4466.0 pmol/l and was above the normal plasma level in all patients. The intra-articular temperature was negatively correlated with the joint fluid concentration of NPY-LI. Moreover, patients with low intra-articular temperature and high concentration of NPY-LI had a shorter duration of TMJ symptoms than those with high intra-articular temperature and low concentration of NPY-LI.

Topics: Adult; Aged; Arthritis; Arthritis, Psoriatic; Arthritis, Rheumatoid; Body Temperature; Female; Humans; Male; Middle Aged; Neuropeptide Y; Spondylitis, Ankylosing; Synovial Fluid; Temporomandibular Joint Disorders; Time Factors

Arthroscopy was performed on 18 patients (19 joints) with temporomandibular joint arthropathy. Arthroscopic investigation revealed that 12 patients had disk derangement, including 3 patients with rheumatoid arthritis. Six patients had osteoarthrosis, including one patient with rheumatoid arthritis. Synovial fluid content of substance P-like immunoreactivity (SP-LI), neurokinin A (NKA-LI), calcitonin gene-related peptide (CGRP-LI), neuropeptide Y (NPY-LI) and vasoactive intestinal polypeptide (VIP-LI) were analysed using radioimmunoassay technique. All peptides analysed were found, although in various concentrations, in the different joints. There were no significant differences in concentrations of the peptides in the synovial fluid between patients in the various groups. No significant correlation was found between clinical symptoms and signs, arthroscopic findings, or use of analgesic/anti-inflammatory medication versus concentrations of peptides in the synovial fluid. In comparison with earlier findings in the knee joint significantly higher concentrations of SP-LI, CGRP-LI and NPY-LI were found in the TMJ.

Topics: Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Arthroscopy; Calcitonin Gene-Related Peptide; Cartilage, Articular; Female; Humans; Male; Middle Aged; Neurokinin A; Neuropeptide Y; Neuropeptides; Osteoarthritis; Substance P; Synovial Fluid; Synovitis; Temporomandibular Joint; Temporomandibular Joint Disorders; Vasoactive Intestinal Peptide

There is evidence that neuropeptides play a role in the development of arthritis. Synovial fluid from arthritic temporomandibular joints in patients with rheumatoid arthritis was therefore investigated for presence of the neuropeptides calcitonin gene-related peptide, substance P, neurokinin A and neuropeptide Y. All four peptides were found in the synovial fluid above plasma level, but calcitonin gene-related peptide showed the highest concentration and substance P the lowest.

Topics: Adult; Arthritis, Rheumatoid; Calcitonin Gene-Related Peptide; Female; Humans; Neurokinin A; Neuropeptide Y; Neuropeptides; Substance P; Synovial Fluid; Temporomandibular Joint Disorders