Premium
ANTI‐INFLAMMATORY AND ANTI‐NOCICEPTIVE ACTIVITY OF RISEDRONATE IN EXPERIMENTAL PAIN MODELS IN RATS AND MICE
Author(s) -
Carvalho Aline P,
Bezerra Mirna M,
Girão Virgínia CC,
Cunha Fernando Q,
Rocha Francisco AC
Publication year - 2006
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2006.04413.x
Subject(s) - nociception , medicine , pharmacology , anesthesia , receptor
SUMMARY1 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)‐α and leukotriene (LT) B 4 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 µg/kg, s.c.) and compared with vehicle (saline)‐treated (NT) animals. One group of rats was cotreated with the µ‐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 µg/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 µg/kg, significantly inhibited TNF‐α release as compared with the NT group (39.4 ± 9.8 vs 145.6 ± 43.3 pg/mL TNF‐α, respectively). 8 Risedronate, at 50 and 100 µg/kg, significantly inhibited LTB 4 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‐α and LTB 4 release and is not linked to an endogenous opioid‐release mechanism.