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Paw Inflammation (paw + inflammation)
Selected AbstractsThe importance of brain PGE2 inhibition versus paw PGE2 inhibition as a mechanism for the separation of analgesic and antipyretic effects of lornoxicam in rats with paw inflammationJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2009Dr Nobuko Futaki Abstract Objectives Lornoxicam is a non-selective cyclooxygenase inhibitor that exhibits strong analgesic and anti-inflammatory effects but a weak antipyretic effect in rat models. Our aim was to investigate the mechanism of separation of potencies or analgesic and antipyretic effecls of lornoxicam in relatioin to its effect on prostaglandin E2 (PGE2) production in the inflammatory paw and the brain. Methods A model of acute or chronic paw inflammation was induced by Freund's complete adjuvant injection into the rat paw. Lornoxicam (0.01,1 mg/kg), celecoxib (0.3,30 mg/kg) or loxoprofen (0.3,30 mg/kg) was administered orally to the rats and the analgesic and antipyretic effects were compared. The paw hyperalgesia was assessed using the Randall,Selitto test or the flexion test. Dorsal subcutaneous body temperature was measured as indicator of pyresis. After the measurement of activities, the rats were sacrificed and the PGE2 content in the paw exudate, cerebrospinal fluid or brain hypothalamus was measured by enzme-immunoassay. Key findings In a chronic model of arthritis, lornoxicam, celecoxib and loxoprofen reduced hyperalgesia with an effective dose that provides 50% inhibition (ED50) of 0.083, 3.9 and 4.3 mg/kg respectively, whereas the effective dose of these drugs in pyresis was 0.58, 0.31 and 0.71 mg/kg respectively. These drugs significantly reduced the PGE2 level in paw exudate and the cerebrospinal fluid. In acute oedematous rats, lornoxicam 0.16 mg/kg, celecoxib 4 mg/kg and loxoprofen 2.4 mg/kg significantly reduced hyperalgesia to a similar extent. On the other hand, lornnoxicam did not affect the elevated body temperature, whereas celecoxib and loxoprofen siginificantly reduced the pyrexia to almost the normal level. These drugs significantly reduced the PGE2 level in inflamed paw exudate lo almost the normal level. On the other hand, lornoxicam did not change PGE2 level in the brain hypothalamus, whereas celecoxib and loxoprofen strongly decreased it. Conclusions Lornoxicam exhibits strong analgesic but weak antipyretic effects in rats with paw inflammation. Such a separation of effects is related to its efficacy in the reduction of PGE2 levels in the paw and brain hypothalamus. [source] Inflammatory Pain Reduction In Rats By Local Treatment With oATP, A Selective Inhibitor Of P2X7 ATP ReceptorJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2001G Dell'Antonio Peptide neurotransmitters, as substance P or ATP, are released during inflammatiory processes by the nerve endings of sensory fibers. ATP is also released from the cytoplasm of damaged cells at the site of inflammation. It acts at the level of many P2X subtypes of purinoreceptors. The receptor for extracellular ATP named P2Z/P2X7 is selectively blocked by the periodate oxidized ATP (oATP). We have hypothesized that P2X subunits present on peripheral sensory nerve terminals, able to initiate a nociceptive signal, could be blocked by local treatment with oATP, so inducing pain relief. Male inbred Fisher rats weighing about 250 g were used. Unilateral inflammation into rat hind paw was induced by intraplantar injection of Freund's complete adjuvant (FCA). The following signs of inflammation, from 3 to 48 h after FCA injection, were detected: increased paw volume, increased paw temperature and hyperalgesia. The latter was evaluated using an algesiometric test wich measured the paw pressure threshold (PPT, expressed in g). We treated some rats, bearing paw inflammation by 12 h, with local injection of 56 ,M oATP. We showed a significant reduction of hyperalgesia in treated rats (PPT = 190 ± 2.3 in inflamed paw of oATP treated vs. PPT = 60 ± 1.6 in inflamed paw of untreated rats, at 60 min following oATP innoculation). We showed also that treatment with oATP was more efficient than treatment with diclofenac in reducing local inflammatory pain (PPT expressed as percentage of the maximum possible effect = 60 ± 0.5, at 120 min following intraplantar administration of oATP, vs. 25 ± 1.9 at the same time following intraplantar administration of diclofenac). The use of polyclonal antibody anti P2X7 receptor to perform immunohistochemical analysis of inflamed tissue, showed a reduction of receptor expression at the level of nerve endings in sections obtained from rat paw treated with oATP with respect to sections obtained from untreated rats. Such an effect was independent on the recruitment of immunocytes in inflamed tissue. Our results demonstrate that ATP exerts a key role in the pathophysiology of peripheral inflammation and that oATP may be effective in treating inflammatory pain. [source] Synergistic Interactions Between a KCNQ Channel Opener and an Opioid: Flupirtine and Morphine in Rat Pain Models Including Neuropathic PainPAIN MEDICINE, Issue 7 2007C Goodchild Purpose of the study:, Flupirtine is an established clinical analgesic for mild to moderate musculoskeletal pain states. It has recently been shown to be a KCNQ 2,3 potassium channel opener. These experiments were performed to see if this property could be useful in treating more severe pain states characterised by central sensitisation with the drug either given alone or in combination with morphine. Methods:, Experiments were performed in rats in an observer blinded fashion with vehicle controls. Non sedating doses of flupirtine, morphine and combinations containing both drugs were defined using the rotarod technique. Dose response relationships were determined for non sedating doses of both drugs given alone and together in combination in causing antinociception in three nociception paradigms: electrical pain; carrageenan paw inflammation; streptozotocin-induced diabetic neuropathy. Results:, Flupirtine and morphine when given alone caused slight to moderate antinociception in all three paradigms. Flupirtine also caused significant increases in morphine antinociception in all three models. In carrageenan paw inflammation complete reversal of carrageenan-induced hyperalgesia was caused by 10 mg/kg flupirtine in combination with 0.4 mg/kg morphine. These doses of the two drugs were ineffective when given alone but the combination caused complete antinociception in this model of inflammatory pain. In the diabetic neuropathy model (see figure) morphine 3.2 mg/kg given alone caused significant antinociception but the size of that response was significantly less than that caused by a lower dose of morphine (1.6 mg/kg shown to be ineffective when it was given alone) given in combination with flupirtine 10 mg/kg (p < 0.001; one way ANOVA). Conclusions:, Flupirtine should be investigated as an adjunct analgesic with opioids for the management of patients with severe pain states involving central sensitization. [source] Fructose-1,6-bisphosphate reduces inflammatory pain-like behaviour in mice: role of adenosine acting on A1 receptorsBRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2009DA Valério Background and purpose:, D-Fructose-1,6-bisphosphate (FBP) is an intermediate in the glycolytic pathway, exerting pharmacological actions on inflammation by inhibiting cytokine production or interfering with adenosine production. Here, the possible antinociceptive effect of FBP and its mechanism of action in the carrageenin paw inflammation model in mice were addressed, focusing on the two mechanisms described above. Experimental approach:, Mechanical hyperalgesia (decrease in the nociceptive threshold) was evaluated by the electronic pressure-metre test; cytokine levels were measured by elisa and adenosine was determined by high performance liquid chromatography. Key results:, Pretreatment of mice with FBP reduced hyperalgesia induced by intraplantar injection of carrageenin (up to 54%), tumour necrosis factor , (40%), interleukin-1 , (46%), CXCL1 (33%), prostaglandin E2 (41%) or dopamine (55%). However, FBP treatment did not alter carrageenin-induced cytokine (tumour necrosis factor , and interleukin-1 ,) or chemokine (CXCL1) production. On the other hand, the antinociceptive effect of FBP was prevented by systemic and intraplantar treatment with an adenosine A1 receptor antagonist (8-cyclopentyl-1,3-dipropylxanthine), suggesting that the FBP effect is mediated by peripheral adenosine acting on A1 receptors. Giving FBP to mice increased adenosine levels in plasma, and adenosine treatment of paw inflammation presented a similar antinociceptive mechanism to that of FBP. Conclusions and implications:, In addition to anti-inflammatory action, FBP also presents an antinociceptive effect upon inflammatory hyperalgesia. Its mechanism of action seems dependent on adenosine production but not on modulation of hyperalgesic cytokine/chemokine production. In turn, adenosine acts peripherally on its A1 receptor inhibiting hyperalgesia. FBP may have possible therapeutic applications in reducing inflammatory pain. [source] | ||||||||||