Analgesic Effect Of Diclofenac Research Articles

Study the analgesic effect of diclofenac and silymarin coadministration in chicks

Study the analgesic effect of diclofenac and silymarin coadministration in chicks

The Comparison of Anti-inflammatory and Analgesic Effect of Diclofenac Alone with Combined Treatment with Diclofenac and Serratiopeptidase in Patients having Osteoarthritis of Knee Joint

Oral proteolytic enzymes like serratiopeptidase are very commonly used by clinicians either alone or in combination with non-steroidal anti-inflammatory drugs for analgesia and anti-inflammatory purpose. As the activity of these drugs is not proved in trials, and they are not listed in any country's official pharmacopoeia, it was planned to study their effect in osteoarthritis patients. Two groups (n= 30 each) of diagnosed knee osteoarthritis patients, were treated with diclofenac 50 mg twice a day (BID) and serratiopeptidase 10mg three times a day (TID) + Diclofenac 50 mg BID for two weeks. The pain and difficulty in daily activities were assessed by Visual Analogue Scale (VAS) and Western Ontario and Mc Masters Universities Osteoarthritis (WOMAC OA) index scale before and after the treatment. Highly significant improvement in both scales was seen in both groups. There was no statistically significant difference in the improvements found in both groups. Addition of serratiopeptidase has not potentiated analgesic and anti-inflammatory effects of diclofenac. Thus, the analgesic and anti-inflammatory efficacy of serratiopeptidase are not proved.

A diclofenac suppository–nabumetone combination therapy for arthritic pain relief and a monitoring method for the diclofenac binding capacity of HSA site II in rheumatoid arthritis

Diclofenac suppository, a non-steroidal anti-inflammatory drug (NSAID), is used widely in rheumatoid arthritis (RA) patients with severe arthritic pain. As the binding percentage of diclofenac to serum proteins is high, its free (unbound) concentration after rectal administration is low. To increase temporarily the free concentration of diclofenac and to enhance its analgesic effect by inhibiting the protein binding of diclofenac, the analgesic effect of diclofenac was examined before and after the start of an inhibitor administration to RA patients with insufficient control of arthritic pain, and the protein binding capacity of diclofenac was evaluated. Binding experiments were performed by ultrafiltration, and arthritic pain was recorded by the face scale. Free fractions of diazepam and diclofenac were augmented by increasing 6-methoxy-2-naphthylacetic acid (6-MNA; the active metabolite of the NSAID nabumetone) concentrations. The free fraction of diazepam increased after the start of nabumetone administration to RA patients, and arthritic pain relief was observed. These results suggest that 6-MNA has an inhibitory effect on the protein binding of diclofenac and the free fraction of diazepam can be used to evaluate the binding capacity of diclofenac. It is considered that diclofenac suppository-nabumetone combination therapy and the method for protein binding monitoring by diazepam can positively benefit RA patients with insufficient control of arthritic pain.

Targeting A-type K+ channels in primary sensory neurons for bone cancer pain in a rat model

Cancer pain is one of the most severe types of chronic pain, and the most common cancer pain is bone cancer pain. The treatment of bone cancer pain remains a clinical challenge. Here, we report firstly that A-type K+ channels in dorsal root ganglion (DRG) are involved in the neuropathy of rat bone cancer pain and are a new target for diclofenac, a nonsteroidal anti-inflammatory drug that can be used for therapy for this distinct pain. There are dynamically functional changes of the A-type K+ channels in DRG neurons during bone cancer pain. The A-type K+ currents that mainly express in isolectin B4-positive small DRG neurons are increased on post-tumor day 14 (PTD 14), then faded but still remained at a higher level on PTD 21. Correspondingly, the expression levels of A-type K+ channel Kv1.4, Kv3.4, and Kv4.3 showed time-dependent changes during bone cancer pain. Diclofenac enhances A-type K+ currents in the DRG neurons and attenuates bone cancer pain in a dose-dependent manner. The analgesic effect of diclofenac can be reversed or prevented by A-type K+ channel blocker 4-AP or pandinotoxin-Kα, also by siRNA targeted against rat Kv1.4 or Kv4.3. Repeated diclofenac administration decreased soft tissue swelling adjacent to the tumor and attenuated bone destruction. These results indicate that peripheral A-type K+ channels were involved in the neuropathy of rat bone cancer pain. Targeting A-type K+ channels in primary sensory neurons may provide a novel mechanism-based therapeutic strategy for bone cancer pain.

Gaseous superoxide potentiation of the effect of nonnarcotic analgesics in low doses.

The action of inhalation of gaseous superoxide on the effects of low doses of nonnarcotic analgesics was studied on volunteers in the little finger compression test. After administration of placebo, inhalation of gaseous superoxide produced a negligible transient decrease in pain tolerance threshold. Inhalation of gaseous superoxide potentiated the effects of threshold doses of novalgin and aspirin and prolonged their action, but did not modulate the analgesic effect of diclofenac. It is assumed that the potentiating effect of superoxide on the action of analgesics is related to inhibition of monoamine oxidases leading to accumulation of monoamines in the brain.

Misoprostol therapeutics revisited.

Misoprostol, a prostaglandin E1 analog, is a racemate of four stereoisomers. On administration it rapidly de-esterifies to its active form, misoprostolic acid. Misoprostolic acid is 85% albumin bound and has a half-life of approximately 30 minutes. It is excreted in urine as inactive metabolites. No significant drug interactions have been reported. Besides its gastrointestinal protective and uterotonic activities, misoprostol regulates various immunologic cascades. It inhibits platelet-activating factor and leukocyte adherence, and modulates adhesion molecule expression. It protects against gut irradiation injury, experimental gastric cancer, enteropathy, and constipation. It improves nutrient absorption in cystic fibrosis. Misoprostol has utility in acetaminophen and ethanol hepatotoxicity, hepatitis, and fibrosis. It is effective in asthmatics and aspirin-sensitive asthmatic and allergic patients. It lowers cholesterol and severity of peripheral vascular diseases, prolongs survival of cardiac and kidney transplantation, synergizes cyclosporine, and protects against cyclosporine-induced renal damage. It works against drug-induced renal damage, interstitial cystitis, lupus nephritis, and hepatorenal syndrome. It is useful in periodontal disease and dental repair. Misoprostol enhances glycosoaminoglycan synthesis in cartilage after injury. It prevents ultraviolet-induced cataracts and reduces intraocular pressure in glaucoma and ocular hypertension. It synergizes antiinflammatory and analgesic effects of diclofenac or colchicine and has been administered to treat trigeminal neuralgic pain. It reduces chemotherapy-induced hair loss and recovery time from burn injury, and is effective in treating sepsis, multiple sclerosis, and pancreatitis.

Diclofenac and NS-398, a selective cyclooxygenase-2 inhibitor, decrease agonist-induced contractions of the pig isolated ureter.

Non-steroidal anti-inflammatory drugs (NSAIDs) are currently considered a first-line treatment of renal colic. Their action has been ascribed to the inhibition of renal prostaglandin synthesis, which decreases renal blood flow and diuresis, and consequently lowers the pressure in the renal pelvis and ureter. However, the effects of NSAIDs on induced contractions of ureteral smooth muscle have received little attention. Also, there is a lack of clinically relevant spasmolytic drugs for the ureter. Therefore, we studied the influence of the non-selective cyclooxygenase (COX) inhibitor diclofenac, a NSAID drug customarily used in the treatment of renal colic, and of NS-398, a selective COX-2 inhibitor, on induced contractions of the pig ureter. Serotonin (0.1-30 microM), norepinephrine (0.1-30 microM) and neurokinin A (0.03-10 microM) induced reproducible concentration-dependent contractions, which were inhibited by diclofenac and NS-398 (10-300 microM) in a concentration-dependent manner. The sensitivity of neurokinin A-induced contractions to diclofenac was 3-4 times greater than that of the amines. Depending on the concentration, inhibition ranged between 25 and 96% of the initially induced contractile activity. In the presence of inhibitors, supramaximal concentrations of agonists were unable to trigger recuperation of the initially induced contractions. Prostaglandin F2alpha did not reverse the effect of diclofenac on agonist-induced contractions. Removal of diclofenac or NS-398 from the organ baths showed that the inhibition was totally reversible. Thus, the non-selective COX inhibitor diclofenac and the selective COX-2 inhibitor NS-398 are almost equipotent in reducing agonist-induced contractions in the isolated porcine ureter. Although the clinical relevance of this spasmolytic effect remains to be demonstrated, the data suggest that patients suffering from renal colic may benefit not only from the anti-diuretic and analgesic effects of diclofenac, but also from its potential spasmolytic properties. Moreover, selective COX-2 inhibitors may have clinical potential, as they may cause fewer side effects.

Mechanism of diclofenac analgesia: direct blockade of inflammatory sensitization

Indomethacin, a typical cyclo-oxygenase inhibitor, acts as an analgesic by preventing the hyperalgesia induced by prostaglandins during inflammation. Analgesics of the dipyrone type directly block the sensitization of nociceptors. In the present investigation, the analgesic effect of diclofenac was compared with that of indomethacin in two algesimetric tests which permit discrimination between the two types of analgesic: the rat knee joint incapacitation and the rat paw hyperalgesia tests. The analgesics were given either pre- or posttreatment relative to the induction of hyperalgesia with carrageenin or prostaglandin E 2. In both tests intraperitoneal pretreatment with indomethacin was equally or slightly more potent than diclofenac. Posttreatment with diclofenac was more effective than posttreatment with indomethacin. T0is was particularly evident in the paw hyperalgesia test in which posttreatment with indomethacin was not effective while diclofenac caused dose-dependent analgesia. When nociception was induced by PGE 2 in both tests, the administration of indomethacin directly into the knee joint or rat paw had no effect while diclofenac continued to cause dose-dependent analgesia. Thus, diclofenac has a direct effect on ongoing hyperalgesia in addition to its ability to block cyclo-oxygenase. Naloxone and N-methyl-nalorphine did not affect diclofenac analgesia, thus indicating that the analgesic effect of the latter is independent of a central or peripheral opioid effect. Local administration of agents which inhibit the formation of nitric oxide ( N G - monomethyl- L - arginine ) or inhibit the activation of guanylate cyclase by nitric oxide (methylene blue) abolished diclofenac-induced analgesia. Thus, the present results indicate that the principal analgesic action of diclofenac is not associated with the prevention of sensitization but is due to the functional down-regulation of sensitized, peripheral pain receptors. This functional down-regulation seems to be the result of stimulation of the cGMP system via the arginine-nitric oxide pathway, a mechanism of analgesic action postulated for peripheral analgesics which directly block ongoing hyperalgesia.

Diclofenac Increases Beta-Endorphin Plasma Concentrations

Plasma and ventricular cerebro-spinal fluid (CSF) Beta-endorphin concentrations were evaluated after chromatographic separation in patients carrying a ventricular shunt before and after the administration of diclofenac or placebo. In the same subjects the ventricular CSF concentrations of the serotonin and the catecholamine metabolites 5-hydroxyindole-acetic acid (5-HIAA), homovanillic acid (HVA) and MOPEG were also evaluated. Plasma, but not ventricular, Beta-endorphin concentrations increased significantly after diclofenac, while placebo was ineffective. No significant changes in ventricular 5-HIAA, HVA or MOPEG levels were observed. These data suggest a role for Beta-endorphin in the analgesic effect of diclofenac.

Analgesic effect of diclofenac on postoperative pain prevention

Analgesic effect of diclofenac on postoperative pain prevention