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Anti-inflammatory and anti-nociceptive activity of risedronate in experimental pain models in rats and mice.
Clin Exp Pharmacol Physiol. 2006 Jul; 33(7):601-6.CE

Abstract

1. The antinociceptive effect of risedronate in experimental pain models in rats and mice was investigated in the present study. 2. Rats received zymosan intra-articularly (i.art.) into the right knee joint and the nociceptive response was assessed using the articular incapacitation test. Joint washouts were used for determining cell influx, tumour necrosis factor (TNF)-alpha and leukotriene (LT) B4 levels. 3. Mice received either zymosan (1 mg) or acetic acid (0.6%) i.p. and the nociceptive response was measured as the number of writhings between 0 and 30 min after the stimuli. Control animals received i.p. injections of saline. 4. Groups were pretreated with risedronate (5-500 microg/kg, s.c.) and compared with vehicle (saline)-treated (NT) animals. One group of rats was cotreated with the micro-opioid receptor antagonist naloxone (2 mg/kg, s.c.) prior to risedronate, followed by 1 mg zymosan i.art. 5. Risedronate, at 100 and 500 microg/kg, significantly and dose-dependently inhibited the nociceptive response in the writhings test (P < 0.05), inhibiting responses to acetic acid by 65.4 and 49.2%, respectively, and to zymosan by 72.9 and 71.9%, respectively. 6. Pretreatment with risedronate also significantly (P < 0.05) and dose-dependently inhibited the articular incapacitation in zymosan-arthritis. 7. Risedronate, at 50 microg/kg, significantly inhibited TNF-alpha release as compared with the NT group (39.4 +/- 9.8 vs 145.6 +/- 43.3 pg/mL TNF-alpha, respectively). 8. Risedronate, at 50 and 100 microg/kg, significantly inhibited LTB4 release into the joints compared with the NT group (2883.1 +/- 73.2, 1911.5 +/- 205.3 and 4709.9 +/- 237.2 pg/mL, respectively). These effects of risedronate were associated with a significant reduction in the inflammatory cell infiltration. 9. Cotreatment with risedronate and naloxone did not reverse the antinociceptive effects of risedronate in zymosan-arthritis. 10. This is the first demonstration that risedronate displays intrinsic antihypernociceptive activity. This effect is associated with reduced cell infiltration and inhibition of TNF-alpha and LTB4 release and is not linked to an endogenous opioid-release mechanism.

Authors+Show Affiliations

Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceará, Ceará, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16789926

Citation

Carvalho, Aline P., et al. "Anti-inflammatory and Anti-nociceptive Activity of Risedronate in Experimental Pain Models in Rats and Mice." Clinical and Experimental Pharmacology & Physiology, vol. 33, no. 7, 2006, pp. 601-6.
Carvalho AP, Bezerra MM, Girão VC, et al. Anti-inflammatory and anti-nociceptive activity of risedronate in experimental pain models in rats and mice. Clin Exp Pharmacol Physiol. 2006;33(7):601-6.
Carvalho, A. P., Bezerra, M. M., Girão, V. C., Cunha, F. Q., & Rocha, F. A. (2006). Anti-inflammatory and anti-nociceptive activity of risedronate in experimental pain models in rats and mice. Clinical and Experimental Pharmacology & Physiology, 33(7), 601-6.
Carvalho AP, et al. Anti-inflammatory and Anti-nociceptive Activity of Risedronate in Experimental Pain Models in Rats and Mice. Clin Exp Pharmacol Physiol. 2006;33(7):601-6. PubMed PMID: 16789926.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anti-inflammatory and anti-nociceptive activity of risedronate in experimental pain models in rats and mice. AU - Carvalho,Aline P, AU - Bezerra,Mirna M, AU - Girão,Virgínia C C, AU - Cunha,Fernando Q, AU - Rocha,Francisco A C, PY - 2006/6/23/pubmed PY - 2007/8/10/medline PY - 2006/6/23/entrez SP - 601 EP - 6 JF - Clinical and experimental pharmacology & physiology JO - Clin Exp Pharmacol Physiol VL - 33 IS - 7 N2 - 1. The antinociceptive effect of risedronate in experimental pain models in rats and mice was investigated in the present study. 2. Rats received zymosan intra-articularly (i.art.) into the right knee joint and the nociceptive response was assessed using the articular incapacitation test. Joint washouts were used for determining cell influx, tumour necrosis factor (TNF)-alpha and leukotriene (LT) B4 levels. 3. Mice received either zymosan (1 mg) or acetic acid (0.6%) i.p. and the nociceptive response was measured as the number of writhings between 0 and 30 min after the stimuli. Control animals received i.p. injections of saline. 4. Groups were pretreated with risedronate (5-500 microg/kg, s.c.) and compared with vehicle (saline)-treated (NT) animals. One group of rats was cotreated with the micro-opioid receptor antagonist naloxone (2 mg/kg, s.c.) prior to risedronate, followed by 1 mg zymosan i.art. 5. Risedronate, at 100 and 500 microg/kg, significantly and dose-dependently inhibited the nociceptive response in the writhings test (P < 0.05), inhibiting responses to acetic acid by 65.4 and 49.2%, respectively, and to zymosan by 72.9 and 71.9%, respectively. 6. Pretreatment with risedronate also significantly (P < 0.05) and dose-dependently inhibited the articular incapacitation in zymosan-arthritis. 7. Risedronate, at 50 microg/kg, significantly inhibited TNF-alpha release as compared with the NT group (39.4 +/- 9.8 vs 145.6 +/- 43.3 pg/mL TNF-alpha, respectively). 8. Risedronate, at 50 and 100 microg/kg, significantly inhibited LTB4 release into the joints compared with the NT group (2883.1 +/- 73.2, 1911.5 +/- 205.3 and 4709.9 +/- 237.2 pg/mL, respectively). These effects of risedronate were associated with a significant reduction in the inflammatory cell infiltration. 9. Cotreatment with risedronate and naloxone did not reverse the antinociceptive effects of risedronate in zymosan-arthritis. 10. This is the first demonstration that risedronate displays intrinsic antihypernociceptive activity. This effect is associated with reduced cell infiltration and inhibition of TNF-alpha and LTB4 release and is not linked to an endogenous opioid-release mechanism. SN - 0305-1870 UR - https://www.unboundmedicine.com/medline/citation/16789926/Anti_inflammatory_and_anti_nociceptive_activity_of_risedronate_in_experimental_pain_models_in_rats_and_mice_ L2 - https://doi.org/10.1111/j.1440-1681.2006.04413.x DB - PRIME DP - Unbound Medicine ER -