Pharmacological Characterization of the Chronic Constriction Injury Model of Neuropathic Pain

The chronic constriction injury model is a rat model of neuropathic pain based on a unilateral loose ligation of the sciatic nerve. The aim of the present study was to test its sensitivity to various clinically validated and experimental drugs. Mechanical allodynia and thermal hyperalgesia developed within one week post-surgery and were reliably present for at least 7 weeks. Mechanical allodynia was strongly attenuated by morphine (minimal effective dose in brackets: 8 mg/kg, p.o.) and the cannabinoids Delta9-tetrahydrocannabinol (3 mg/kg, p.o.) and (-)-cis-3-[2-hydroxy-4(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl) cyclohexanol (CP 55,940; 0.05 mg/kg, i.p.), and weakly/moderately attenuated by the anticonvulsants gabapentin (50 mg/kg, i.p.) and carbamazepine (32 mg/kg, i.p.), the muscle relaxant baclofen (3 mg/kg, i.p.), and the adenosine kinase inhibitor 4-amino-5-(3-bromophenyl)-7-(6-morpholino-pyridin-3-yl)pyrido[2,3-d]pyrimidine (ABT-702; 30 mg/kg, i.p.). Thermal hyperalgesia was strongly attenuated by morphine (16 mg/kg, p.o.), Delta9-tetrahydrocannabinol (6 mg/kg, p.o.), CP 55,940 (0.025 mg/kg, i.p.), carbamazepine (32 mg/kg, i.p.) and the antidepressant amitriptyline (32 mg/kg, p.o.), and weakly/moderately attenuated by gabapentin (50 mg/kg, i.p.), the anti-inflammatory cyclooxygenase-2 inhibitor rofecoxib (30 mg/kg, i.p.) and the adenosine A1 receptor positive allosteric modulator 2-amino-4,5,6,7-tetrahydrobenzo(b)thiophen-3-yl 4-chlorophenylmethanone (T62; 30 mg/kg, i.p.). Both symptoms were hardly or not affected by the nonselective N-methyl-d-aspartate receptor antagonists ketamine and dizocilpine, and the N-methyl-d-aspartate receptor NR2B-selective antagonists ifenprodil and R-(R*,S*)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenyl-methyl)-1-piperidine propranol (Ro 25-6981). The finding that mechanical allodynia and/or thermal hyperalgesia are attenuated by various established compounds further supports the validity of the chronic constriction injury model for the study of neuropathic pain and its use for the identification of novel treatments.