Cremophor EL

Paclitaxel (Tocris, Bristol, UK) was dissolved in a solution made up of 50% Cremophor EL and 50% absolute ethanol to a concentration of 6 mg/ml and stored at −20°C for a maximum of 14 days. It was then diluted in normal saline (NaCl 0.9%) to a final concentration of 0.2 mg/ml just before administration. The vehicle for paclitaxel was diluted at the time of injection with normal saline in the same proportion as the paclitaxel solution. Paclitaxel 2 mg/kg or its vehicle were administered to the mice intraperitoneally, in a volume of 10 ml/kg, once per day for 5 consecutive days. This treatment regimen has been reported to produce painful neuropathy in mice [6 (link)].
COL-3 (a gift from Galderma, Research and Development SNC, Les Templier, France) was dissolved in 1% methylcellulose and administered to mice by oral gavage in a volume of 12.5 ml/kg body mass. COL-3 (4–40 mg/kg) was coadministered with paclitaxel or its vehicle daily for 5 days. The mice were assessed for the development of neuropathic pain (thermal hyperalgesia) and those that received paclitaxel plus COL-3 were compared with the mice treated with the paclitaxel plus vehicle (for COL-3) only.
Reaction latencies to the hot plate test were measured before treatment (baseline latency) and on days 7, 10, 14, 17, 21 and 28 after the first injection of drugs (paclitaxel or COL-3). Briefly, the mice were individually placed on a hot plate (Panlab SL, Barcelona, Spain) with the temperature adjusted to 55 ± 1°C. The time to the first sign of nociception, paw licking, flinching or jump response to avoid the heat was recorded and the animal immediately removed from the hot plate. A cutoff period of 20 s was maintained to avoid damage to the paws. The observer (S.S.P.) was blinded to the treatment the animal received. The percentage change in reaction latency was calculated as follows: [(response latency after drug treatment – pretreatment baseline latency)/pretreatment baseline latency] ×100.