Effects of intrathecal lidocaine on hyperalgesia and allodynia following chronic constriction injury in rats.
The present study investigated the effects of different doses of intrathecal lidocaine on established thermal hyperalgesia and tactile allodynia in the chronic constriction injury model of neuropathic pain, defined the effective drug dose range, the duration of pain-relief effects, and the influence of this treatment on the body and tissues. Male Sprague-Dawley rats were divided into five groups and received intrathecal saline or lidocaine (2, 6.5, 15, and 35 mg/kg) 7 days after loose sciatic ligation. Respiratory depression and hemodynamic instability were found to become more severe as doses of lidocaine increased during intrathecal therapy. Two animals in the group receiving 35 mg/kg lidocaine developed pulmonary oedema and died. Behavioral tests indicated that 6.5, 15, and 35 mg/kg intrathecal lidocaine showed different degrees of reversal of thermal hyperalgesia, and lasted for 2-8 days, while 2 mg/kg lidocaine did not. The inhibition of tactile allodynia was only observed in rats receiving 15 and 35 mg/kg lidocaine, and the anti-allodynic effects were identical in these two groups. Histopathologic examinations on the spinal cords revealed mild changes in rats receiving 2-15 mg/kg lidocaine. However, lesions were severe after administration of 35 mg/kg lidocaine. These findings indicate that intrathecal lidocaine has prolonged therapeutic effects on established neuropathic pain. The balance between sympathetic and parasympathetic nervous activities could be well preserved in most cases, except for 35 mg/kg. Considering the ratio between useful effects and side effects, doses of 15 mg/kg are suitable for intrathecal injection for relief of neuropathic pain.
Tian
Jie
J
Department of Anesthesiology, Renji Hospital, Medical School of Shanghai Jiaotong University, Shanghai, China.
Gu
Yiwen
Y
Su
Diansan
D
Wu
Yichao
Y
Wang
Xiangrui
X
D000779:Anesthetics, Local / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001522:Behavior, Animal; D002908:Chronic Disease; D003251:Constriction, Pathologic / Q000150:complications* / Q000473:pathology; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D007278:Injections, Spinal; D008012:Lidocaine / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D010146:Pain / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D010147:Pain Measurement / Q000187:drug effects; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D013116:Spinal Cord / Q000473:pathology
D000779:Anesthetics, Local; D008012:Lidocaine