Article

Increased gene expression and production of spinal cyclooxygenase 1 and 2 during experimental osteoarthritis pain

Department of Pharmacology, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
Physiological research / Academia Scientiarum Bohemoslovaca (Impact Factor: 1.49). 01/2009; 58(3):419-25.
Source: PubMed

ABSTRACT Knowledge on the involvement of spinal COX-1 and COX-2 in pain due to osteoarthritis could be useful for better understanding of its pathogenesis and therapy. In this study we have investigated a long-term pattern of expression and production of spinal COX-1 and COX-2 in the model of osteoarthritis induced in rats by injection of monoiodoacetate (MIA) into the knee joint. MIA injection produced thermal hyperalgesia (assessed by the plantar test) and tactile allodynia (measured with von Frey hairs). The pain measures reached maximum on the fifht day, then remained relatively stable. The expression of spinal COX-2 mRNA reached maximum on day 5 (5.2 times; P<0.001) and remained increased until day 31 (4.9 times; P<0.001). Expression of spinal COX-1 mRNA increased gradually reaching maximum on the day 31 (4.5 times; P<0.001) when the relative expression of both genes was almost equal. The production of both proteins was almost similar at the beginning of the experiment. The highest production of COX-2 protein was observed on day 5 after the induction of osteoarthritis (increased 3.9 times). The levels of COX-1 protein increased gradually with maximum on day 31 (3.4 times). The present findings indicate that not only expression of COX-2 mRNA but also that of COX-1 mRNA is significantly increased in the spine during osteoarthritis pain. Thus, in contrast to inflammatory pain, the upregulation of spinal COX-1 may be important in osteoarthritis pain.

Download full-text

Full-text

Available from: Peter Zanvit, Sep 01, 2015
0 Followers
 · 
102 Views
 · 
70 Downloads
  • Source
    • "Despite the characterization of knee joint pain processing in the periphery of sensitized rats, very little is known about the state of processing in the spinal dorsal horn. Cellular and molecular changes do occur in the spinal cord such as increases in COX-1/-2 [24], proinflammatory cytokines [25], pain related neuropeptides [26], [27], activation of mitogen activated protein kinases [28] and microglial activation [29]–[31], suggesting that pain processing in the spinal cord is important to the behavioral effects in this model. Wide dynamic range neurons receiving direct input from the MIA sensitized knee joint have shown increased spontaneous spiking activity [13] but the majority of spinal cord physiology studies focus on secondary sensitization arising in the ipsilateral paw [32], [33]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Sensory processing in the spinal cord during disease states can reveal mechanisms for novel treatments, yet very little is known about pain processing at this level in the most commonly used animal models of articular pain. Here we report a test of the prediction that two clinically effective compounds, naproxen (an NSAID) and oxycodone (an opiate), are efficacious in reducing the response of spinal dorsal horn neurons to noxious knee joint rotation in the monosodium iodoacetate (MIA) sensitized rat. The overall objective for these experiments was to develop a high quality in vivo electrophysiology assay to confidently test novel compounds for efficacy against pain. Given the recent calls for improved preclinical experimental quality we also developed and implemented an Assay Capability Tool to determine the quality of our assay and ensure the quality of our results. Spinal dorsal horn neurons receiving input from the hind limb knee joint were recorded in anesthetized rats 14 days after they were sensitized with 1 mg of MIA. Intravenous administered oxycodone and naproxen were each tested separately for their effects on phasic, tonic, ongoing and afterdischarge action potential counts in response to innocuous and noxious knee joint rotation. Oxycodone reduced tonic spike counts more than the other measures, doing so by up to 85%. Tonic counts were therefore designated the primary endpoint when testing naproxen which reduced counts by up to 81%. Both reductions occurred at doses consistent with clinically effective doses for osteoarthritis. These results demonstrate that clinically effective doses of standard treatments for osteoarthritis reduce pain processing measured at the level of the spinal cord for two different mechanisms. The Assay Capability Tool helped to guide experimental design leading to a high quality and robust preclinical assay to use in discovering novel treatments for pain.
    PLoS ONE 08/2014; 9(8):e106108. DOI:10.1371/journal.pone.0106108 · 3.23 Impact Factor
  • Source
    • "Thermal hyperalgesia is important symptom of neuropathic pain, therefore, we employed thermal hyperalgesia to investigate the effect of SMT in the MIA-induced OA pain. Thermal hyperalgesia has also been used in the MIA-induced OA in rats in earlier studies to study the effect of different categories of drugs in OA pain (Procházková et al., 2009; Okun et al., 2012). "
    Pharmacology Biochemistry and Behavior 01/2013; 103(4):764-772. · 2.82 Impact Factor
  • Source
    • "Thermal hyperalgesia is important symptom of neuropathic pain, therefore, we employed thermal hyperalgesia to investigate the effect of SMT in the MIA-induced OA pain. Thermal hyperalgesia has also been used in the MIA-induced OA in rats in earlier studies to study the effect of different categories of drugs in OA pain (Procházková et al., 2009; Okun et al., 2012). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Much information is available on the role of nitric oxide (NO) in osteoarthritis (OA). However, its role has not been studied in the monosodium iodoacetate (MIA)-induced model of osteoarthritic pain. The present study was undertaken in rats to investigate the effect of iNOS inhibitor S-methylisothiourea (SMT) in MIA-induced osteoathritic pain and disease progression in rats. Osteoarthritis was produced by single intra-articular injection of the MIA in the right knee joint on day 0. Treatment groups were orally gavazed with different doses of SMT (10, 30 and 100mg/kg) and etoricoxib (10mg/kg) daily for 21days. On days 0, 3, 7, 14 and 21, pain was measured and histopathology of right knee joint was done on day 21. SMT produced analgesia in a dose-dependent manner as shown by mechanical, heat hyperalgesia, knee vocalization, knee squeeze test, and spontaneous motor activity test. SMT reduced NO production in synovial fluid. Histopathological findings indicated that SMT reduced disease progression as evident from complete cartilage formation in rats treated with SMT at 30mg/kg. In conclusion, the results indicate that SMT attenuates the MIA-induced pain and histopathological changes in the knee joint. The antinociceptive and antiarthritic effects of SMT were mediated by inhibiting cartilage damage and suppression of NO in synovial fluid. It is suggested that SMT has potential as a therapeutic modality in the treatment of osteoarthritis.
    Pharmacology Biochemistry and Behavior 01/2012; 103(4):764-772. DOI:10.1016/j.pbb.2012.12.013. · 2.82 Impact Factor
Show more