Inflammatory pain in the rabbit: A new, efficient method for measuring mechanical hyperalgesia in the hind paw

Dong, Hong; Sun, Hong; Magal, Ella; Ding, Xiao; Kumar, Gondi; Chen, Jian Jeffrey; Johnson, Eileen; Manning, Barton H.

doi:10.1016/j.jneumeth.2007.09.028

Cited by 13 publications

(17 citation statements)

References 41 publications

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“…Xu et al 19 have determined the paw withdrawal latencies to be 8 to 10 secs in the normal mouse (baseline). Dong et al 12 Also, Dong et al, 12 in an inflammatory pain model in rabbits, determined a decrease (from 67.64 to 37.54 g) in basal threshold response to mechanical stimulation. In this study, the threshold values of mechanical stimulus and paw thermal withdrawal latency were observed to decrease to 29.33 T 9 g and 4.50 T 0.5 secs 10 days after the ligation, respectively, as a result of neuropathic pain.…”

Section: Discussionmentioning

confidence: 99%

“…The level of neuropathic pain can be indicated by tactile allodynia and hyperalgesia. 2 To determine the threshold value of mechanical stimulation, von Frey filaments with variable pressure ranges (1Y75 g) were used for rats, 3 whereas rigid electroYvon Frey filaments were used for the rabbits, 12 and thermal hyperalgesia was assessed by hot plate or radiant heating (45Y58.5-C). 11 In this study, the thermal latencies were recorded automatically as the time taken from the onset of the thermal stimulus to withdrawal of the hind paw from the heat source during the hot plate test, performed at 58.5-C. We used a standardized algometer to evaluate the rabbits' response to the mechanical stimulus.…”

Section: Discussionmentioning

confidence: 99%

“…Using a previous rabbit study, we determined that a sample size of 6 rabbits per group was required. 12 The SD for differences in mechanical withdrawal threshold was estimated to be 7.2 g. Using this estimate, and > = 0.05 and A = 0.2, the proposed sample size of 6 rabbits per group was expected to be adequate to detect a difference of 7.2 g in rabbit mechanical withdrawal threshold, through power analysis using a sample size software (Version 10.1.6Y* 1993Y 2009 MedCalc Software). P G 0.05 was considered statistically significant.…”

Section: Statisticsmentioning

confidence: 99%

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The Efficiency of Pulsed Radiofrequency Application on L5 and L6 Dorsal Roots in Rabbits Developing Neuropathic Pain

Aksu¹,

Uğur²,

Biçer³

et al. 2010

Regional Anesthesia and Pain Medicine

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Statisticsmentioning

confidence: 99%

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The Efficiency of Pulsed Radiofrequency Application on L5 and L6 Dorsal Roots in Rabbits Developing Neuropathic Pain

Aksu¹,

Uğur²,

Biçer³

et al. 2010

Regional Anesthesia and Pain Medicine

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“…In mice, the hyperalgesic effect of carrageenan 3-5 h after challenge was mediated by B 2 but not B 1 receptors, however, from 7 h after carrageenan injection hyperalgesia started to be mediated by B 1 receptors while the contribution of B 2 receptors diminished (126). Likewise, in a novel inflammatory pain model in the rabbit, carrageenan-induced mechanical hyperalgesia was prevented by icatibant, whereas an established hyperalgesia was reversed by desArg 9 ,Leu 8 -bradykinin (157).…”

Section: And Table 1)mentioning

confidence: 97%

Sensory and Signaling Mechanisms of Bradykinin, Eicosanoids, Platelet-Activating Factor, and Nitric Oxide in Peripheral Nociceptors

Pethő

Reeh

2012

Physiological Reviews

244

200

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Peripheral mediators can contribute to the development and maintenance of inflammatory and neuropathic pain and its concomitants (hyperalgesia and allodynia) via two mechanisms. Activation or excitation by these substances of nociceptive nerve endings or fibers implicates generation of action potentials which then travel to the central nervous system and may induce pain sensation. Sensitization of nociceptors refers to their increased responsiveness to either thermal, mechanical, or chemical stimuli that may be translated to corresponding hyperalgesias. This review aims to give an account of the excitatory and sensitizing actions of inflammatory mediators including bradykinin, prostaglandins, thromboxanes, leukotrienes, platelet-activating factor, and nitric oxide on nociceptive primary afferent neurons. Manifestations, receptor molecules, and intracellular signaling mechanisms of the effects of these mediators are discussed in detail. With regard to signaling, most data reported have been obtained from transfected nonneuronal cells and somata of cultured sensory neurons as these structures are more accessible to direct study of sensory and signal transduction. The peripheral processes of sensory neurons, where painful stimuli actually affect the nociceptors in vivo, show marked differences with respect to biophysics, ultrastructure, and equipment with receptors and ion channels compared with cellular models. Therefore, an effort was made to highlight signaling mechanisms for which supporting data from molecular, cellular, and behavioral models are consistent with findings that reflect properties of peripheral nociceptive nerve endings. Identified molecular elements of these signaling pathways may serve as validated targets for development of novel types of analgesic drugs.

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“…Indeed, 27 h after the carrageenan injection, the inflammation is likely to be physiologically resolved. This has been previously reported (Dong et al ., ) and is evident in the present data (Fig ). Hence, the carrageenan‐induced inflammation model probably does not produce hyperalgesia at that time and the % MPR value might not be valid (Barter & Kwiatkowski, ).…”

Section: Discussionmentioning

confidence: 97%

Pharmacokinetic/pharmacodynamic evaluation of grapiprant in a carrageenan‐induced inflammatory pain model in the rabbit

Vito

Salvadori²,

Poapolathep

et al. 2016

Vet Pharm & Therapeutics

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Grapiprant is the novel selective EP4 receptor inhibitor recently issued on the veterinary market for dogs affected by osteoarthritis. The aim of this study was twofold: to evaluate the pharmacokinetics and the pharmacodynamics of grapiprant in the induced inflammatory pain model in the rabbit after a single IV injection of 2 mg/kg; to compare the thermal antinociception effect after 2 mg/kg IV grapiprant, with that generated by 0.5 mg/kg meloxicam SC injected. Rabbits (n = 12) were randomly assigned to two crossover studies (single-dose, two-period crossover). The first study group A (n = 3) received a single IV dose of grapiprant at 2 mg/kg dissolved in ethanol. Group B (n = 3) received a single IV injection of ethanol (equivalent volume to grapiprant volume) at the same site. The second study group C (n = 3) received a single SC dose of meloxicam at 0.5 mg/kg. Group D (n = 3) received a single SC injection of 15% ethanol (equivalent volume to grapiprant volume) at the same site. After a 2-week washout period, the groups were rotated and the experiments repeated. Blood samples (0.7 mL) were collected from the right ear artery at assigned times and grapiprant plasma concentrations determined by a validated HPLC-FL method. Three hours prior to administration of the drugs, inflammation was induced by SC injection of lambda carrageenan (200 μL, 3% in physiological saline) under the plantar surface of the right hind paw. At a similar time to the blood collection, an infrared thermal stimuli (40 °C) was applied to the plantar surface of the rabbits' hindlimbs to evaluate the thermal withdrawal latency (TWL). The thermal antinociceptive effect was expressed as maximum possible response (% MPR). Grapiprant plasma concentrations were detectable up to the 10-h time point (concentration range 17-7495 ng/mL). The grapiprant-treated group showed a significant increase in TWL from 1 h and up to 10 h after drug administration compared to the control. In contrast, the meloxicam group showed a significant increase in TWL from 4 up to 10 h after drug administration, compared to control. The maximal MPR% was not statistically different between the grapiprant and meloxicam group from 4 to 8 h, while significant differences were shown at 1, 1.5, 2, 10 and 24 h. Given these findings, grapiprant appears to be an attractive option for antinociception in rabbits, due to its rapid onset and extended duration of effect.

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Inflammatory pain in the rabbit: A new, efficient method for measuring mechanical hyperalgesia in the hind paw

Cited by 13 publications

References 41 publications

The Efficiency of Pulsed Radiofrequency Application on L5 and L6 Dorsal Roots in Rabbits Developing Neuropathic Pain

The Efficiency of Pulsed Radiofrequency Application on L5 and L6 Dorsal Roots in Rabbits Developing Neuropathic Pain

Sensory and Signaling Mechanisms of Bradykinin, Eicosanoids, Platelet-Activating Factor, and Nitric Oxide in Peripheral Nociceptors

Pharmacokinetic/pharmacodynamic evaluation of grapiprant in a carrageenan‐induced inflammatory pain model in the rabbit

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