The prolonged analgesic effect of epidural ropivacaine in a rat model of neuropathic pain.
BACKGROUND
In clinical practice, the analgesic effects of epidurally administered local anesthetics on chronic pain sometimes outlast the duration of drug action expected from their pharmacokinetics. To investigate the underlying mechanisms of this prolonged effect, we examined the effects of ropivacaine, a local anesthetic, on pain-related behavior in a rat model of neuropathic pain. We also analyzed changes in the expression of nerve growth factor (NGF), which is involved in plasticity of the nociceptive circuit after nerve injury.


METHODS
In a rat model of neuropathic pain produced by chronic constrictive injury (CCI) of the sciatic nerve, thermal hyperalgesia, and mechanical allodynia were observed from Day 3 after surgery. Ropivacaine or saline was administered through an epidural catheter once a day, every day, and from Days 7-13 after the CCI operation. NGF content was measured in the L4 dorsal root ganglion, the hindpaw skin, the L4/5 dorsal spinal cord, and the sciatic nerve, using enzyme immunoassay.


RESULTS
The latency to withdrawal from thermal stimuli on the ipsilateral paw pads of CCI rats was significantly increased 4 days after the beginning of ropivacaine treatment, and thermal hyperalgesia was almost fully relieved. Similarly, mechanical allodynia was partially reduced after ropivacaine treatment. NGF content was increased in the L4 dorsal root ganglion on the ipsilateral, but not the contralateral, side, in CCI rats treated with ropivacaine.


CONCLUSIONS
Repetitive administration of ropivacaine into the epidural space in CCI rats exerts an analgesic effect, possibly by inducing a plastic change in the nociceptive circuit.
Sato
Chiyo
C
Department of Pharmacology, Nippon Medical School, Tokyo, Japan.
Sakai
Atsushi
A
Ikeda
Yumiko
Y
Suzuki
Hidenori
H
Sakamoto
Atsuhiro
A
D000577:Amides / Q000008:administration & dosage / Q000494:pharmacology*; D015360:Analgesia, Epidural; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D006358:Hot Temperature; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D020932:Nerve Growth Factor / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D000077212:Ropivacaine; D020426:Sciatic Neuropathy / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D012585:Sciatica / Q000150:complications / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D013997:Time Factors; D014110:Touch
D000577:Amides; D000779:Anesthetics, Local; D000077212:Ropivacaine; D020932:Nerve Growth Factor