neuropeptide-y and Osteoarthritis--Knee

The precise etiology of knee osteoarthritis (KOA) pain remains highly controversial and there is no known effective treatment. Due to the known and suggested effects of neuropeptide Y (NPY) on pain, we have sought to investigate the relationship between the concentration of NPY in synovial fluid of knee, pain of KOA, and structural severity of KOA.. One hundred KOA patients and twenty healthy participants (control group) were recruited. The pain and the radiographic grade of KOA were assessed separately by Hideo Watanabe's pain score and Tomihisa Koshino's scoring system. Synovial fluid of knee from all participants was collected with arthrocentesis. Radioimmunoassay was used to examine the concentration of NPY in synovial fluid of knee.. Concentrations of NPY in synovial fluid were significantly higher in KOA patients (124.7 ± 33.4 pg/mL) compared with controls (64.8 ± 26.3 pg/mL) (p = 0.0297). According to Hideo Watanabe's pain score, 100 KOA patients were divided into 5 subgroups: no pain (n = 12), mild pain (n = 25), moderate pain (n = 37), strong pain (n = 19) and severe pain (n = 7). Within the KOA group, significantly higher concentrations of NPY were found in each subgroup as pain intensified (no pain 81.4 ± 11.7 pg/mL, mild pain 99.1 ± 23.2 pg/mL, moderate pain 119.9 ± 31.5 pg/mL, strong pain 171.2 ± 37.3 pg/mL and severe pain 197.3 ± 41.9 pg/mL). Meanwhile, according to Tomihisa Koshino's scoring system, 100 KOA patients were divided into 3 subgroups: early stage (n = 30), middle stage (n = 53), advanced stage (n = 17). Concentrations of NPY in middle and advanced stage groups of KOA patients were significant higher than early stage group of KOA patients (early stage 96.4 ± 27.1 pg/mL, middle stage 153.3 ± 16.9 pg/mL, advanced stage 149.5 ± 36.7 pg/mL) (p = 0.0163, p = 0.0352). Concentrations of NPY in advanced stage group of KOA patients has no significant difference compare with middle stage group of KOA patients (p = 0. 2175).. This study demonstrated the presence and variation of concentrations of NPY in the KOA joint fluid, suggesting a role for NPY as a putative regulator of pain transmission and perception in KOA pain.

Topics: Adult; Aged; Biomarkers; Female; Humans; Male; Middle Aged; Neuropeptide Y; Osteoarthritis, Knee; Pain; Pain Measurement; Synovial Fluid

It was recently reported that the mono-iodoacetate (MIA) experimental model of osteoarthritis (OA) courses with changes of neurons innervating the affected joints that are commonly interpreted as a neuronal response to axonal injury. To better characterize these changes, we evaluated the expression of two markers of neuronal damage, ATF-3 and NPY, and the growth associated protein GAP-43, in primary afferent neurons of OA animals injected with three different doses of MIA (0.3, 1 or 2 mg). Measurements were performed at days 3, 7, 14, 21 and 31 post-MIA injection.. OA animals showed the characteristic histopathological changes of the joints and the accompanying nociceptive behaviour, evaluated by the Knee-Bed and CatWalk tests. An increase of ATF-3 expression was detected in the DRG of OA animals as early as 3 days after the injection of 1 or 2 mg of MIA and 7 days after the injection of 0.3 mg. NPY expression was increased in animals injected with 1 or 2 mg of MIA, at day 3 or in all time-points, respectively. From day 7 onwards there was a massive increase of GAP-43 expression in ATF-3 cells.. The expression of the neuronal injury markers ATF-3 and NPY as well as an up-regulation of GAP-43 expression, indicative of peripheral fibre regeneration, suggests that axonal injury and a regeneration response may be happening in this model of OA. This opens new perspectives in the unravelling of the physiopathology of the human disease.

Topics: Activating Transcription Factor 3; Animals; Behavior, Animal; Biomarkers; Disease Models, Animal; Ganglia, Spinal; GAP-43 Protein; Humans; Immunohistochemistry; Iodoacetic Acid; Knee Joint; Lumbar Vertebrae; Male; Neurons; Neuropeptide Y; Osteoarthritis, Knee; Rats; Rats, Wistar

Chronic inflammation associated with osteoarthritis (OA) alters normal responses and modifies the functionality of the articular vasculature. Altered responsiveness of the vasculature may be due to excessive neural activity associated with chronic pain and inflammation, or from the production of inflammatory mediators which induce vasodilation. Using laser speckle perfusion imaging (LSPI), blood flow to the medial collateral ligament (MCL) of adult rabbits was measured in denervated ACL transected knees (n = 6) and compared to unoperated control (n = 6) and 6-week anterial cruciate ligament (ACL)-transected knees (n = 6). Phenylephrine and neuropeptide Y were applied to the MCL vasculature in topical boluses of 100 microL (dose range 10(-14) to 10(-8) mol and 10(-14) to 10(-9) mol, respectively). Denervation diminished vasoconstrictive responsiveness to phenylephrine compared to both control and ACL-transected knees. Denervation minimally enhanced vascular responses to neuropeptide Y (NPY) compared to ACL deficiency alone, which nevertheless remained significantly diminished from control responses. To evaluate the potential role of inflammatory dilators in the diminished contractile responses, phenylephrine was coadministered with histamine, substance P, and prostaglandin E(2). High-dose histamine, and low-dose substance P and PGE(2) were able to inhibit contractile responses in the MCL of control knees. Excessive neural input does not mediate diminished vasoconstrictive responses in the ACL transected knee; inflammatory mediators may play a role in the deficient vascular responsiveness of the ACL transected knee.

Topics: Adrenergic alpha-Agonists; Animals; Anterior Cruciate Ligament Injuries; Denervation; Disease Models, Animal; Dose-Response Relationship, Drug; Inflammation; Inflammation Mediators; Medial Collateral Ligament, Knee; Neuropeptide Y; Osteoarthritis, Knee; Pain; Phenylephrine; Physical Stimulation; Rabbits; Regional Blood Flow; Vasoconstriction

Synovial tissue was obtained from medial, lateral, and suprapatellar sites of 21 knees (15 patients) with medial compartmental osteoarthritis at surgery. All patients reported pain around the medial joint of their knees while walking and climbing stairs. For investigation of the synovial innervation, six samples were stained with modified gold chloride and the others with an immunohistochemical method using antisera against neuropeptides. The extent of synovitis in each part was scored using a new 10-point scale. The results showed that the synovium had an extensive neural network in the somatic and autonomic nervous systems. Neuropeptides were most abundant, with an especially large number of substance P and calcitonin gene related peptide immunoreactive free nerve endings. Some of the substance P positive nerve endings were surrounded by monocytes. Substance P and calcitonin gene related peptide were found more frequently in the medial than in the lateral or suprapatellar areas. Substance P positive free nerve endings showed more dendritic morphologic features in the medial region than did those in the lateral and suprapatellar regions, and small nerves were accompanied by newly developed vessels in synovial villi. In the medial region, the synovitis was more remarkable than in the lateral region. These findings suggest that free nerve endings containing substance P may modulate inflammation and the pain pathway in osteoarthritis.

Topics: Aged; Calcitonin Gene-Related Peptide; Female; Humans; Immunohistochemistry; Male; Middle Aged; Neuropeptide Y; Neuropeptides; Osteoarthritis, Knee; Substance P; Synovial Membrane