Paclitaxel-induced neuropathic hypersensitivity in mice: responses in 10 inbred mouse strains.
Mechanical allodynia, or hypersensitivity to tactile stimuli, is a frequent clinical symptom of neuropathy. Large interindividual differences have been observed in neuropathic pain, both in susceptibility to its development and in its severity. Identification of genetic factors relevant to this variability would be of obvious utility. Although many animal models of neuropathic pain following peripheral nerve injury have been developed, most involve intricate surgeries and are thus poorly suited for large-scale linkage mapping investigations in the mouse. Recently, a schedule of intraperitoneal injections of the chemotherapeutic agent, paclitaxel (Taxol(R)), has been shown to produce a long-lasting, bilateral neuropathy in the rat, featuring hypersensitivity to mechanical, thermal and cold stimuli. We present here a survey of the responses of 10 inbred mouse strains to paclitaxel injections. Virtually all strains developed statistically significant mechanical allodynia, with one strain, DBA/2J, exhibiting especially robust changes. Strain sensitivities to paclitaxel-induced mechanical allodynia were similar to those obtained previously using a surgical model of neuropathic pain, supporting our contention that genetic sensitivity to mechanical allodynia is independent of the precise mode of induction. Using sensitive DBA/2 mice and a resistant strain, C57BL/6J, for comparison, we further characterized the paclitaxel model in mice by examining cold allodynia and thermal hyperalgesia. Both strains displayed equivalent cold allodynia but neither strain developed thermal hyperalgesia. The present data confirm a genetic component in mechanical allodynia using this model, while dissociating mechanical hypersensitivity from other pain modalities.
Smith
Shad B
SB
Department of Psychology Centre for Research on Pain, McGill University, 1205 Dr. Penfield Ave., Montreal QC, Canada H3A 1B1.
Crager
Sara E
SE
Mogil
Jeffrey S
JS
D000704:Analysis of Variance; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D003080:Cold Temperature; D004195:Disease Models, Animal; D005260:Female; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced* / Q000235:genetics*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D017239:Paclitaxel / Q000633:toxicity*; D010146:Pain / Q000235:genetics*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced*; D010812:Physical Stimulation; D013045:Species Specificity
D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel