Characterisation of a dynamic allodynia end-point in the rat tibial nerve transection (TNT) model of neuropathic pain

Denise Richardson1, Reem Yahia2, Ian Machin1, Janet Nicholson1. 1Pfizer Inc, Sandwich, Kent, United Kingdom, 2University of Oxford, Oxford, United Kingdom

Dynamic mechanical allodynia, which can be evoked by gentle brushing of the skin, is a common symptom experienced by a sub-group of pain patients (Otto et al., 2003). It affects 20-40% of neuropathic pain (NeP) patients and is largely untreatable, suggesting the need for a method to assess dynamic allodynia (DA) in pre-clinical models of NeP. Static allodynia (SA) is a well characterised endpoint commonly used in pre-clinical studies and has been shown to be present in rats which have tibial nerve transection –induced NeP (Richardson et al., 2008). The aim of the present study was to characterise DA in the TNT model of NeP, alongside the SA end-point.

TNT surgery was performed on anaesthetised male Sprague-Dawley rats (200-250 g, CRUK) (Lee et al., 2000). From 14 days post-surgery rats were trained and static or dynamic responses measured. SA was measured using a modified version of the Dixon up-down von Frey method to produce 50% paw withdrawal threshold (PWT) values (Chaplan et al., 1994), and DA was measured as paw withdrawal latency (PWL) using an adapted version of the cotton bud method (Field et al., 1999) using a brush. Pregabalin (PG) was used as a clinically relevant control agent

Rats displayed a robust SA when tested from day 20 post-surgery in the ipsilateral hindpaw (1.86 ± 0.4 g) compared to contralateral values (12.46 ± 1.2 g), which was maintained up to the last day of testing, 54 days post-surgery. DA developed within and persisted for the same timeframe (6.79 ± 1.7 s ipsilateral vs 14.12 ± 0.3 s contralateral at 20 days post surgery). Following baseline (BL) measurements on day 20 rats were treated with PG (20 mg/k, po).or vehicle (water, 1ml/kg) and tested at 2h post dose. Pregabalin significantly (P < 0.05) reversed both SA (6.9 fold change from BL) and DA (2.9 fold change from BL).

In conclusion, we have demonstrated that rats with TNT-induced NeP exhibit DA from 14 days post surgery and lasting for at least 7 weeks and that DA , like static, can be reversed by pregabalin.

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