A New Animal Model of Vincristine-Induced Nociceptive Peripheral Neuropathy
Section snippets
INTRODUCTION
A complete knowledge of the pathophysiology of neuropathic pain requires the development of additional new models with different aetiologies than those presently used such as the trauma and metabolic models (Bennett and Xie, 1988, Courteix et al., 1993). The absence of knowledge concerning mechanisms of chemotherapy-induced neuropathic pain has hindered the development of new treatment strategies. Vincristine, an antineoplastic agent widely used in cancer therapy for both solid tumors and
Animals
Two hundred and fifty-two male Sprague–Dawley rats (Charles River, St-Aubin-Lès-Elbeuf, France) weighing 160–180 g at the beginning of the experiment were used (nine rats/test per dose). The rats were housed in plastic cages on a 12 h light/12 h dark cycle with access to water and food ad libitum. Room temperature was maintained at 22 °C and relative humidity was usually between 50 and 60%. Animals were allowed a 1 week acclimatisation period before being used in experiments.
Drugs
Vincristine-treated
Assessment of General Toxicity
No rat died in the vincristine groups irrespective of the dose used. All animals received the five injections as scheduled in the protocol.
In the vincristine 50 μg/kg group, body weight was only significantly decreased compared to saline 3 days after the last injection (P<0.05; −5%). Rats receiving 100 μg/kg showed a significantly lower body weight gain compared to saline from the 4th day to the end of the study (P<0.001; −13%). The highest dose, 150 μg/kg, also induced a significant decrease in
DISCUSSION
This study describes a new model of peripheral nociceptive neuropathy produced after toxic injury of the peripheral nervous system by the antineoplastic agent, vincristine. This model displays all the characteristics of a peripheral sensory neuropathy, i.e. behavioural signs as mechanical and thermal allodynia, mechanical and thermal hyperalgesia, and are associated with significant electrophysiological and histological disorders. The lack of motor disorders is very important for a predictive
Acknowledgements
This work was supported by the local committee of the Ligue Contre le Cancer. We wish thank Dr. P. Duprat and Dr. Sylvain Molon-Noblot for advice and support, Dr. A.S. Gross for comments on the manuscript and C. Graulière for technical assistance.
References (46)
- et al.
Vincristine hyperalgesia in the rat: a model of painful vincristine neuropathy in humans
Neuroscience
(1996) - et al.
Description of a short-term Taxol®-induced nociceptive neuropathy in rats
Brain Res.
(2000) - et al.
Neuropeptides and morphological changes in cisplatin-induced dorsal root ganglion neuronopathy
Exp. Neurol.
(1996) - et al.
A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man
Pain
(1988) - et al.
Tactile allodynia and formalin hyperalgesia in streptozocin-diabetic rats: effects of insulin, aldose reductase inhibition and lidocaine
Pain
(1996) - et al.
Quantitative assessment of tactile allodynia in the rat paw
J. Neurosci. Methods
(1994) - et al.
Insulin-like growth factor-I prevents development of a vincristine neuropathy in mice
Brain Res.
(1997) - et al.
Streptozocin-induced diabetic rat: behavioural evidence for a model of chronic pain
Pain
(1993) - et al.
Ganglioside treatment of vincristine-induced neuropathy. An electrophysiological study
Toxicology
(1988) - et al.
Critical evaluation of the streptozotocin model of painful diabetic neuropathy in the rat
Pain
(1999)