Pharmacological characterization and gene expression profiling of an L5/L6 spinal nerve ligation model for neuropathic pain in mice.
L5/L6 spinal nerve ligation (SNL) in rodents induces behavioral signs similar to the symptoms of neuropathic pain in humans. L5/L6 SNL in rats has been well characterized so far, but there have been few studies using mice. In this study, we established an L5/L6 SNL model in mice and examined the effects of known antinociceptive drugs in the model. We also analyzed the changes in gene expression in dorsal root ganglions with special reference to those which are known to change in a neuropathic pain state to validate the model. Mechanical allodynia in the ipsilateral side paw was observed beginning on day 1 and lasted for at least 2 months following surgery. Diclofenac showed no significant effect on the mechanical allodynia. Gabapentin and pregabalin completely reversed allodynia, but they also caused a decrease in locomotor activity. Duloxetine caused a partial recovery of the threshold. Mexiletine completely reversed allodynia, but it also caused sedation or motor impairment. Morphine caused a partial recovery of the threshold and hyper-locomotion. This mouse L5/L6 SNL model represents a robust mechanical allodynia, which shows a similar pharmacological response to that reported in rats and human patients with neuropathic pain. The pattern changes in gene expression also resembled those reported in rats. This model will therefore be useful for investigation of the effects of novel antinociceptive compounds and the mechanisms of neuropathic pain.
Kiso
T
T
Pharmacology Research Labs, Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba-shi, Ibaraki, Japan. tetsuo-kiso@jp.astellas.com
Watabiki
T
T
Tsukamoto
M
M
Okabe
M
M
Kagami
M
M
Nishimura
K
K
Aoki
T
T
Matsuoka
N
N
D000700:Analgesics / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology; D020869:Gene Expression Profiling; D007278:Injections, Spinal; D008026:Ligation; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008959:Models, Neurological; D009043:Motor Activity / Q000187:drug effects; D009414:Nerve Growth Factors / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D010146:Pain / Q000209:etiology / Q000235:genetics*; D010523:Peripheral Nervous System Diseases / Q000150:complications / Q000235:genetics*; D010812:Physical Stimulation; D058919:Purinergic P2 Receptor Antagonists; D058476:Receptors, Purinergic P2X2; D058477:Receptors, Purinergic P2X3; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013127:Spinal Nerves / Q000502:physiology*
D000700:Analgesics; D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D009414:Nerve Growth Factors; D009479:Neuropeptides; C546401:P2RX2 protein, human; C546407:P2RX3 protein, human; C546402:P2rx2 protein, mouse; C546409:P2rx3 protein, mouse; D058919:Purinergic P2 Receptor Antagonists; D058476:Receptors, Purinergic P2X2; D058477:Receptors, Purinergic P2X3